start-ver=1.4 cd-journal=joma no-vol=123 cd-vols= no-issue=17 article-no= start-page=e2536813123 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260422 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A magnesium efflux transporter required for seed development and eating quality in rice en-subtitle= kn-subtitle= en-abstract= kn-abstract=As a staple food for half the world’s population, rice is an important dietary source of magnesium (Mg), an essential mineral for human health. Enhanced Mg accumulation in rice grains has also been linked to eating quality. However, the mechanisms underlying Mg transport to the grains remains poorly understood. Here, we report that OsMGR2, a member belonging to Magnesium Release (MGR) family, is required for Mg accumulation in rice grains. OsMGR2 encodes a plasma membrane-localized transporter that mediates Mg efflux. OsMGR2 is constitutively and highly expressed in the stele tissues of roots, the phloem region of both enlarged and diffused vascular bundles in nodes, and the ovular vascular trace of caryopses. Knockout of this gene results in decreased root-to-shoot translocation and altered distribution of Mg to different organs; less Mg is allocated to the second newest leaf with high Mg requirement for active photosynthesis. The osmgr2 mutants exhibit decreased Mg accumulation in the grain, which are smaller, lighter, and shriveled, but show increased accumulation in the husk. The eating quality of the mutant grains is significantly decreased compared with the wild-type rice. These results indicate that OsMGR2 plays multiple roles within the rice; facilitating the root-to-shoot Mg translocation, mediating phloem-to-xylem Mg transfer at nodes for preferential distribution to the most active leaf, and exporting Mg from maternal vascular tissues of the caryopsis to the grains, processes essential for grain development and eating quality in rice. en-copyright= kn-copyright= en-aut-name=HuangSheng en-aut-sei=Huang en-aut-mei=Sheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HoriKiyosumi en-aut-sei=Hori en-aut-mei=Kiyosumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamajiNaoki en-aut-sei=Yamaji en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshiokaYuma en-aut-sei=Yoshioka en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NingMin en-aut-sei=Ning en-aut-mei=Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagayaYu en-aut-sei=Nagaya en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyajiTakaaki en-aut-sei=Miyaji en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Mitani-UenoNamiki en-aut-sei=Mitani-Ueno en-aut-mei=Namiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=InoueShin-ichiro en-aut-sei=Inoue en-aut-mei=Shin-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KimJune-Sik en-aut-sei=Kim en-aut-mei=June-Sik kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KashinoMiho en-aut-sei=Kashino en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MaJian Feng en-aut-sei=Ma en-aut-mei=Jian Feng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=National Institute of Crop Science, National Agriculture Research Organization kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=9 en-affil=Department of Regulatory Biology, Saitama University kn-affil= affil-num=10 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=11 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=12 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=magnesium kn-keyword=magnesium en-keyword=rice kn-keyword=rice en-keyword=transporter kn-keyword=transporter END start-ver=1.4 cd-journal=joma no-vol=134 cd-vols= no-issue=4 article-no= start-page=225 end-page=231 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cation distribution and diffusion-path topologies of A-site-deficient perovskite LixLa(1−x)/3NbO3 en-subtitle= kn-subtitle= en-abstract= kn-abstract=LixLa(1−x)/3NbO3 with an A-site-deficient perovskite structure was investigated with a focus on the relationship between its atomic configuration and Li+ diffusion properties. To this end, total scattering (diffraction) measurements were performed, and then reverse Monte Carlo modeling using the data was employed to construct the atomic configuration. The results suggest that the partial occupancy of La in the La-poor layer facilitate Li+ diffusion across the layer owing to the volume contraction. Furthermore, topological analyses conducted via persistent homology using the constructed atomic configuration indicate that a large fourfold ring formed by Nb and O is one of the reasons for superior Li+ diffusion in LixLa(1−x)/3NbO3. en-copyright= kn-copyright= en-aut-name=KitamuraNaoto en-aut-sei=Kitamura en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TangYizhong en-aut-sei=Tang en-aut-mei=Yizhong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraKoji en-aut-sei=Kimura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ObayashiIppei en-aut-sei=Obayashi en-aut-mei=Ippei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OnoderaYohei en-aut-sei=Onodera en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakashimaKen en-aut-sei=Nakashima en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshibashiChiaki en-aut-sei=Ishibashi en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IdemotoYasushi en-aut-sei=Idemoto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HayashiKoichi en-aut-sei=Hayashi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science kn-affil= affil-num=2 en-affil=Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science kn-affil= affil-num=3 en-affil=Department of Physical Science and Engineering, Nagoya Institute of Technology kn-affil= affil-num=4 en-affil=Center for Artificial Intelligence and Mathematical Data Science, Okayama University kn-affil= affil-num=5 en-affil=Center for Basic Research on Materials, National Institute for Materials Science kn-affil= affil-num=6 en-affil=Faculty of Materials for Energy, Shimane University kn-affil= affil-num=7 en-affil=Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science kn-affil= affil-num=8 en-affil=Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science kn-affil= affil-num=9 en-affil=Department of Physical Science and Engineering, Nagoya Institute of Technology kn-affil= en-keyword=A-site-deficient perovskite kn-keyword=A-site-deficient perovskite en-keyword=Li+ conduction kn-keyword=Li+ conduction en-keyword=Total scattering kn-keyword=Total scattering en-keyword=Local structure kn-keyword=Local structure en-keyword=Persistent homology kn-keyword=Persistent homology END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=1263 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251009 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phenotypic and potential virulence features of Salmonella enterica serotypes from cancer patients in Kolkata, India en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Salmonella enterica is a leading cause of gastroenteritis and enteric fever. In this study, we sought to investigate the phenotypic and genotypic characteristics of S. enterica isolated from the cancer patients admitted at the Tata Medical Center, Kolkata over a period of eight years (2016–2023).
Methods Salmonella enterica isolates were identified by standard biochemical and serotyping. Antimicrobial susceptibility was tested by disk diffusion method and virulence genes were identified by PCR. The genetic relatedness of strains was determined by pulsed-field gel electrophoresis (PFGE) methods.
Results A total of 122 S. enterica isolates were identified and classified into 18 different serovars. S. Typhimurium (28.7%), S. Kentucky (22.1%), S. Enteritidis (13.9%), S. Typhi (5.7%) and S. Agona (5.7%) were identified as the common serovars. S. enterica infection was more often detected in adults (77.9%) than in children of 6–18 years old (11.4%) and < 5 years of age (10.6%). The maximum number of S. enterica was isolated from blood (52.4%) followed by those isolated from stool (36.9%) and urine (5.7%). S. enterica infections were detected among patients with chronic myelogenous leukemia (CML)/acute lymphoblastic leukemia (ALL) (24.6%) than Hodgkin lymphoma/non-Hodgkin lymphoma (16.4%), multiple myeloma (9.8%), lung adenocarcinoma (9%), prostate adenocarcinoma (6.6%), and endometrium carcinoma (5.7%). S. Kentucky showed a statistically significant association with hematologic malignancies (p < 0.001), whereas S. Enteritidis was significantly present in Hodgkin lymphoma and acute lymphoblastic leukemia/Chronic myelogenous leukemia cancer types (p = 0.004). Most of the S. enterica isolates displayed resistance to erythromycin (62.9%), nalidixic acid (62.9%) and tetracycline (33.9%). Salmonella pathogenicity island (SPI)-associated genes (orgA, ssaQ, misL, invE/A, spi4D, pipA and ttrc) were uniformly present in majority of the isolates. The hyper invasive locus (hilA), Salmonella enterotoxin (stn), Salmonella outer protein (sopB), virulence plasmid (spvC), and plasmid encoded fimbriae (pefA) genes were present in 76%, 69%, 51%, 32% and 17% of the isolates, respectively. Clonal analysis of the representative homologous serovars using pulsed-field gel electrophoresis revealed specific clusters with 40 to 90% similarity within each serotype.
Conclusions Cancer patients are at increased risk of morbidity due to secondary infections, like S. enterica. Continuous monitoring of antimicrobial resistance patterns and virulence gene profiles in S. enterica isolates from this vulnerable group is critical to guide clinical management and treatment strategies. en-copyright= kn-copyright= en-aut-name=ChowdhuryGoutam en-aut-sei=Chowdhury en-aut-mei=Goutam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BhattacharyaSanjay en-aut-sei=Bhattacharya en-aut-mei=Sanjay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GoelGaurav en-aut-sei=Goel en-aut-mei=Gaurav kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChatterjiSoumyadip en-aut-sei=Chatterji en-aut-mei=Soumyadip kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitaharaKei en-aut-sei=Kitahara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhnoAyumu en-aut-sei=Ohno en-aut-mei=Ayumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LewisMelissa Glenda en-aut-sei=Lewis en-aut-mei=Melissa Glenda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=RamamurthyThandavarayan en-aut-sei=Ramamurthy en-aut-mei=Thandavarayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MukhopadhyayAsish K. en-aut-sei=Mukhopadhyay en-aut-mei=Asish K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Collaborative Research Centre of Okayama University for Infectious Diseases at ICMR- NICED kn-affil= affil-num=2 en-affil=Tata Medical Center kn-affil= affil-num=3 en-affil=Tata Medical Center kn-affil= affil-num=4 en-affil=Tata Medical Center kn-affil= affil-num=5 en-affil=Collaborative Research Centre of Okayama University for Infectious Diseases at ICMR- NICED kn-affil= affil-num=6 en-affil=Collaborative Research Centre of Okayama University for Infectious Diseases at ICMR- NICED kn-affil= affil-num=7 en-affil=Division of Biostatistics, ICMR - National Institute for Research in Bacterial Infections kn-affil= affil-num=8 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Bacteriology, ICMR - National Institute for Research in Bacterial Infections kn-affil= affil-num=10 en-affil=Division of Bacteriology, ICMR - National Institute for Research in Bacterial Infections kn-affil= en-keyword=Salmonella enterica kn-keyword=Salmonella enterica en-keyword=Cancer kn-keyword=Cancer en-keyword=Virulence kn-keyword=Virulence en-keyword=Antimicrobial resistance kn-keyword=Antimicrobial resistance en-keyword=PFGE kn-keyword=PFGE END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=5 article-no= start-page=e00824-24 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250527 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sodium butyrate inhibits the expression of virulence factors in Vibrio cholerae by targeting ToxT protein en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cholera, a diarrheal disease caused by the gram-negative bacterium Vibrio cholerae, remains a global health threat in developing countries due to its high transmissibility and increased antibiotic resistance. There is a pressing need for alternative strategies, with an emphasis on anti-virulent approaches to alter the outcome of bacterial infections, given the increase in antimicrobial-resistant strains. V. cholerae causes cholera by secreting virulence factors in the intestinal epithelial cells. These virulence factors facilitate bacterial colonization and cholera toxin production during infection. Here, we demonstrate that sodium butyrate (SB), a small molecule, had no effect on bacterial viability but was effective in suppressing the virulence attributes of V. cholerae. The production of cholera toxin (CT) was significantly reduced in a standard V. cholerae El Tor strain and two clinical isolates when grown in the presence of SB. Analysis of mRNA and protein levels further revealed that SB reduced the expression of the ToxT-dependent virulence genes like tcpA and ctxAB. DNA-protein interaction assays, conducted at cellular (ChIP) and in vitro conditions (EMSA), indicated that SB weakens the binding between ToxT and its downstream promoter DNA, likely by blocking DNA binding. Furthermore, the anti-virulence efficacy of SB was confirmed in animal models. These findings suggest that SB could be developed as an anti-virulence agent against V. cholerae, serving as a potential alternative to conventional antibiotics or as an adjunctive therapy to combat cholera. en-copyright= kn-copyright= en-aut-name=KunduSushmita en-aut-sei=Kundu en-aut-mei=Sushmita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DasSuman en-aut-sei=Das en-aut-mei=Suman kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaitraPriyanka en-aut-sei=Maitra en-aut-mei=Priyanka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HalderProlay en-aut-sei=Halder en-aut-mei=Prolay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KoleyHemanta en-aut-sei=Koley en-aut-mei=Hemanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MukhopadhyayAsish K. en-aut-sei=Mukhopadhyay en-aut-mei=Asish K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=DuttaShanta en-aut-sei=Dutta en-aut-mei=Shanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ChatterjeeNabendu Sekhar en-aut-sei=Chatterjee en-aut-mei=Nabendu Sekhar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=BhattacharyaSushmita en-aut-sei=Bhattacharya en-aut-mei=Sushmita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= affil-num=2 en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= affil-num=3 en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= affil-num=4 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= affil-num=5 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= affil-num=6 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= affil-num=7 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= affil-num=9 en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= affil-num=10 en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= en-keyword=sodium butyrate (SB) kn-keyword=sodium butyrate (SB) en-keyword=inhibitor kn-keyword=inhibitor en-keyword=pathogenesis kn-keyword=pathogenesis en-keyword=Vibrio cholerae kn-keyword=Vibrio cholerae en-keyword=ctxAB kn-keyword=ctxAB en-keyword=antimicrobial resistance kn-keyword=antimicrobial resistance en-keyword=toxin-coregulated pilus (TcpA) kn-keyword=toxin-coregulated pilus (TcpA) END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260409 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rice EMF3 Alleles Adjust Flower Opening Time to Enhance the Seed Setting Rate Under High Temperature Stress en-subtitle= kn-subtitle= en-abstract= kn-abstract=To safeguard global food security against rapid population growth and a warming world, the effective genetic improvement of cereals is imperative. Flower opening time (FOT) critically affects the seed setting rate. In this study, we identified a gene, EARLY-MORNING FLOWERING 3 (EMF3), in which single-nucleotide substitutions strongly modulate FOT in rice in a semi-dominant manner, resulting in wide variation in FOT from earlier to later FOT than the wild-type. EMF3 knock-out mutants showed significantly reduced FOT synchrony and disrupted anther dehiscence, leading to fertilisation failure. EMF3 encodes a plasma membrane-localised polypeptide of 723 amino acids with an armadillo repeat fold and four transmembrane segments. Furthermore, EMF3 is specifically expressed in the anthers starting from nighttime on the day of flowering, with substantial impacts on the transcriptomes of both anther and lodicule, which suggested an exclusive role of EMF3 in flowering events. Modifying EMF3 alleles of O. sativa enabled the adjustment of FOT among Oryza species and subspecies, potentially facilitating cross-fertilisation by overcoming one of the major challenges of inter-specific hybridisation to exploit heterosis. Introducing the EMF3 alleles with the earlier FOT into popular rice cultivars resulted in flowering at an earlier time of day when the temperature was cooler, efficiently increasing seed setting rate under heat stress. This discovery unveils the novel mechanism of anther control of flower opening time through the EMF3 gene, while also enabling the use of EMF3 alleles in breeding strategies for efficient fertilisation for increasing hybrid rice seed production and mitigating future heat-stress damage at flowering. en-copyright= kn-copyright= en-aut-name=IshizakiTakuma en-aut-sei=Ishizaki en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HashidaYoichi en-aut-sei=Hashida en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirabayashiHideyuki en-aut-sei=Hirabayashi en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasakiKazuhiro en-aut-sei=Sasaki en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TokunagaHiroki en-aut-sei=Tokunaga en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Simon‐AdaEliza Vie M. en-aut-sei=Simon‐Ada en-aut-mei=Eliza Vie M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WakayamaMasataka en-aut-sei=Wakayama en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakaiToshiyuki en-aut-sei=Takai en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SaitoHiroki en-aut-sei=Saito en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaganoAtsushi J. en-aut-sei=Nagano en-aut-mei=Atsushi J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakakibaraHitoshi en-aut-sei=Sakakibara en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KojimaMikiko en-aut-sei=Kojima en-aut-mei=Mikiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakebayashiYumiko en-aut-sei=Takebayashi en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KimSung‐Ryul en-aut-sei=Kim en-aut-mei=Sung‐Ryul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MatsushimaRyo en-aut-sei=Matsushima en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ThomsonMichael J. en-aut-sei=Thomson en-aut-mei=Michael J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SugimotoKazuhiko en-aut-sei=Sugimoto en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HibaraKen‐Ichiro en-aut-sei=Hibara en-aut-mei=Ken‐Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshimaruTsutomu en-aut-sei=Ishimaru en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Tropical Agriculture Research Front, Japan International Research Center for Agricultural Sciences (JIRCAS) kn-affil= affil-num=2 en-affil=Faculty of Agriculture, Takasaki University of Health and Welfare kn-affil= affil-num=3 en-affil=Institute of Crop Science, National Agriculture and Food Research Organization (NARO) kn-affil= affil-num=4 en-affil=Biological Resources and Post-Harvest Division, Japan International Research Center for Agricultural Sciences (JIRCAS) kn-affil= affil-num=5 en-affil=Tropical Agriculture Research Front, Japan International Research Center for Agricultural Sciences (JIRCAS) kn-affil= affil-num=6 en-affil=Plant Breeding, Genetics, and Biotechnology Division, International Rice Research Institute (IRRI) kn-affil= affil-num=7 en-affil=Institute for Advanced Biosciences, Keio University kn-affil= affil-num=8 en-affil=Plant Breeding, Genetics, and Biotechnology Division, International Rice Research Institute (IRRI) kn-affil= affil-num=9 en-affil=Tropical Agriculture Research Front, Japan International Research Center for Agricultural Sciences (JIRCAS) kn-affil= affil-num=10 en-affil=Institute for Advanced Biosciences, Keio University kn-affil= affil-num=11 en-affil=Graduate School of Bioagricultural Sciences, Nagoya University kn-affil= affil-num=12 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=13 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=14 en-affil=Rice Breeding Innovations Department, International Rice Research Institute (IRRI) kn-affil= affil-num=15 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=16 en-affil=Plant Breeding, Genetics, and Biotechnology Division International Rice Research Institute (IRRI) Metro Manila Philippines kn-affil= affil-num=17 en-affil=Institute of Crop Science, National Agriculture and Food Research Organization (NARO) kn-affil= affil-num=18 en-affil=18Graduate School of Agricultural Regional Vitalization, Kibi International University kn-affil= affil-num=19 en-affil=Biological Resources and Post-Harvest Division, Japan International Research Center for Agricultural Sciences (JIRCAS) kn-affil= en-keyword=EARLY-MORNING FLOWERING 3 kn-keyword=EARLY-MORNING FLOWERING 3 en-keyword=flower opening time kn-keyword=flower opening time en-keyword=heat stress kn-keyword=heat stress en-keyword=rice kn-keyword=rice en-keyword=seed setting rate kn-keyword=seed setting rate END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis of sulfur- and oxygen-bridged cationic [4]-helicenes mediated by Friedel–Crafts-S N Ar tandem reactions for red-light-driven organophotoredox catalysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=The synthesis of sulfur- and oxygen-bridged cationic [4]-helicenes via a tandem Friedel–Crafts–SNAr reaction of a diaryl sulfide or a diaryl ether with a (thio)salicylic acid has been developed. The sulfur-bridged cationic [4]-helicenes are suitable as catalysts for photoredox reactions under low-energy light sources such as red LED light. en-copyright= kn-copyright= en-aut-name=HasebeRyoga en-aut-sei=Hasebe en-aut-mei=Ryoga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HanadaRumi en-aut-sei=Hanada en-aut-mei=Rumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaYuta en-aut-sei=Tanaka en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotoYuta en-aut-sei=Goto en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakeuchiMio en-aut-sei=Takeuchi en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakamuraHiroyoshi en-aut-sei=Takamura en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KadotaIsao en-aut-sei=Kadota en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaKenta en-aut-sei=Tanaka en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HoshinoYujiro en-aut-sei=Hoshino en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Environment and Information Sciences, Yokohama National University kn-affil= affil-num=2 en-affil=Graduate School of Environment and Information Sciences, Yokohama National University kn-affil= affil-num=3 en-affil=Graduate School of Environment and Information Sciences, Yokohama National University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environment and Information Sciences, Yokohama National University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environment and Information Sciences, Yokohama National University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=7 article-no= start-page=810 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260326 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of Universal Adhesives on Resin Cement–Fiber Post–Core Materials en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study evaluated eleven resin cements used as core build-up materials by examining the following properties: (a) push-out force between root dentin and the fiber post; (b) pull-out force between the fiber post and the core build-up material; (c) shear bond strength of the resin cement to root dentin; (d) flexural strength of the resin cement; and (e) flexural modulus of elasticity of the resin cement. The purpose of this investigation was to clarify the relationships between recently available universal adhesives, core build-up materials, resin cements, and fiber posts. All experiments were performed at two evaluation periods: after 1 day of water storage (Base) and after 20,000 thermocycles (TC 20k). For the push-out test, simulated post spaces were prepared in single-rooted human premolars. The specimens were sectioned perpendicular to the long axis into 2 mm-thick slices and then subjected to push-out testing to assess the bond strength of the dentin–resin cement–fiber post complex. No significant differences in bonding performance were found between Base and TC 20k. These findings suggest that universal adhesives used for pretreatment of multiple substrates in fiber post cementation can provide not only strong but also durable adhesion over time. en-copyright= kn-copyright= en-aut-name=IrieMasao en-aut-sei=Irie en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkadaMasahiro en-aut-sei=Okada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaruoYukinori en-aut-sei=Maruo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkiyamaKenraro en-aut-sei=Akiyama en-aut-mei=Kenraro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsujimotoAkimasa en-aut-sei=Tsujimoto en-aut-mei=Akimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoTakuya en-aut-sei=Matsumoto en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Dental Biomaterials, Graduate School of Dentistry, Tohoku University kn-affil= affil-num=3 en-affil=Department of Prosthodontics, Okayama University kn-affil= affil-num=4 en-affil=Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Health Research Institute, National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=6 en-affil=Department of Operative Dentistry, School of Dentistry, Aichi Gakuin University kn-affil= affil-num=7 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=bonding performance kn-keyword=bonding performance en-keyword=universal adhesive kn-keyword=universal adhesive en-keyword=fiber post kn-keyword=fiber post en-keyword=luting materials kn-keyword=luting materials en-keyword=root dentin kn-keyword=root dentin END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=2 article-no= start-page=831 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Porphyromonas gingivalis Vesicles Control Osteoclast–Macrophage Lineage Fate en-subtitle= kn-subtitle= en-abstract= kn-abstract=Porphyromonas gingivalis (Pg), a keystone pathogen of chronic periodontitis, releases outer membrane vesicles (OMVs) that act as nanoscale vehicles to disseminate virulence factors within periodontal tissues and systemically beyond the oral cavity. Although Pg-OMVs are increasingly recognized as critical mediators of host–pathogen interactions, their effects on the differentiation and function of monocyte–macrophage/osteoclast lineage cells remain unclear. Here, we examined the impact of Pg-OMVs on the differentiation of RAW264.7 monocyte/macrophage-like cells into osteoclasts (OC) and/or macrophages (MΦ) in the presence of receptor activator of nuclear factor-κB ligand (RANKL). OMVs were isolated from Pg W83 and applied to RANKL-primed RAW264.7 cells using three distinct stimulation schedules: (1) simultaneous treatment with Pg-OMVs and RANKL at Day 0; (2) RANKL priming at Day 0 followed by Pg-OMV stimulation at Day 1; and (3) RANKL priming at Day 0 followed by Pg-OMV stimulation at Day 3. In all schedules, cells were cultured for 7 days from the initial RANKL exposure. Remarkably, simultaneous exposure to Pg-OMVs and RANKL (Schedule 1) markedly suppressed osteoclastogenesis (OC-genesis) while promoting M1 macrophage polarization. In contrast, delayed Pg-OMV stimulation of RANKL-primed cells (Schedules 2 and 3) significantly enhanced OC-genesis while reducing M1 polarization. These schedule-dependent effects were consistent with altered expression of osteoclastogenic markers, including dc-stamp, oc-stamp, nfatc1, and acp5. Importantly, a monoclonal antibody against OC-STAMP counteracted the Pg-OMV-induced upregulation of OC-genesis in Schedules 2 and 3. Furthermore, levels of Pg-OMV phagocytosis were inversely correlated with osteoclast formation. Finally, co-stimulation with RANKL and Pg-OMVs (Schedule 1) enhanced macrophage migratory capacity, whereas delayed stimulation with Pg-OMVs (Schedules 2 and 3) did not. Collectively, these findings indicate that Pg-OMVs exert stage-specific effects on the OC/MΦ lineage: stimulation at early stages of RANKL priming suppresses OC-genesis and promotes M1 polarization, whereas stimulation at later stages enhances OC-genesis without inducing M1 differentiation. Thus, Pg-OMVs may critically influence the fate of the OC/MΦ unit in periodontal lesions, contributing to disease progression and tissue destruction. en-copyright= kn-copyright= en-aut-name=LeonElizabeth en-aut-sei=Leon en-aut-mei=Elizabeth kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraShin en-aut-sei=Nakamura en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShindoSatoru en-aut-sei=Shindo en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PastoreMaria Rita en-aut-sei=Pastore en-aut-mei=Maria Rita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KumagaiTomoki en-aut-sei=Kumagai en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HeidariAlireza en-aut-sei=Heidari en-aut-mei=Alireza kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AbdolahiniaElaheh Dalir en-aut-sei=Abdolahinia en-aut-mei=Elaheh Dalir kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UedaTomoya en-aut-sei=Ueda en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MemidaTakumi en-aut-sei=Memida en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Duran-PinedoAna en-aut-sei=Duran-Pinedo en-aut-mei=Ana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=Frias-LopezJorge en-aut-sei=Frias-Lopez en-aut-mei=Jorge kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HanXiaozhe en-aut-sei=Han en-aut-mei=Xiaozhe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ChenXin en-aut-sei=Chen en-aut-mei=Xin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HuangShengyuan en-aut-sei=Huang en-aut-mei=Shengyuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=CaoGuoqin en-aut-sei=Cao en-aut-mei=Guoqin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=RuizSunniva en-aut-sei=Ruiz en-aut-mei=Sunniva kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=PotempaJan en-aut-sei=Potempa en-aut-mei=Jan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawaiToshihisa en-aut-sei=Kawai en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=2 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=4 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=5 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=6 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=7 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=8 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=9 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=10 en-affil=Department of Oral Biology, College of Dentistry, University of Florida kn-affil= affil-num=11 en-affil=Department of Oral Biology, College of Dentistry, University of Florida kn-affil= affil-num=12 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=13 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=14 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=15 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=16 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=17 en-affil=Department of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville kn-affil= affil-num=18 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA kn-affil= en-keyword=Porphyromonas gingivalis kn-keyword=Porphyromonas gingivalis en-keyword=outer membrane vesicle kn-keyword=outer membrane vesicle en-keyword=periodontitis pathogenesis kn-keyword=periodontitis pathogenesis en-keyword=macrophage polarization kn-keyword=macrophage polarization en-keyword=osteoclastogenesis kn-keyword=osteoclastogenesis en-keyword=OC/MΦ unit kn-keyword=OC/MΦ unit END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=42 end-page=50 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biosensing method of growth diagnosis in the forced culture of strawberries ―Development of crop-identification algorithms― en-subtitle= kn-subtitle= en-abstract= kn-abstract=An image-processing algorithm for identifying individual crops is developed for labor-savings and time-series biological information collection. Information including the leaf development frequency are diagnostic indicators of strawberry growth. The algorithm is designed for drones in greenhouses that cannot acquire location information using the global navigation satellite system (GNSS). Drones fly over crop rows and sequentially assign identification numbers (IDs) to crops. Object-detection artificial intelligence (AI) is used to estimate the crop zone, and the ID is based on the crops number difference between frames. The previous misdetection rate was 1.06 %, failing to identify crops, which decreases to 0.31 % using the proposed algorithm. Furthermore, because there are no failures in consecutive frames, IDs are assigned to all crops correctly. en-copyright= kn-copyright= en-aut-name=TSUBOTAShogo en-aut-sei=TSUBOTA en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NAMBAKazuhiko en-aut-sei=NAMBA en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KASEIShota en-aut-sei=KASEI en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FUKATSUTokihiro en-aut-sei=FUKATSU en-aut-mei=Tokihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Institute of Agricultural Machinery, National Agriculture and Food Research Organization kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Institute of Agricultural Machinery, National Agriculture and Food Research Organization kn-affil= affil-num=4 en-affil=Institute of Agricultural Machinery, National Agriculture and Food Research Organization kn-affil= en-keyword=strawberry kn-keyword=strawberry en-keyword=forcing culture kn-keyword=forcing culture en-keyword=image-processing kn-keyword=image-processing en-keyword=object-detection kn-keyword=object-detection en-keyword=identification of individual crops kn-keyword=identification of individual crops en-keyword=drones kn-keyword=drones END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=6 article-no= start-page=657 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Adolescent screen use in the pre-internet era and subsequent health and well-being: an outcome-wide longitudinal study en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study used data from the National Longitudinal Study of Adolescent to Adult Health (Add Health, N = 11,054) to assess whether increases in screen-based leisure during adolescence (Wave II, from 1996) predicted adult well-being (Wave IV, from 2008-09), adjusting for a wide range of covariates (Wave I, from 1995). Using an outcome-wide analytic approach, we examined associations between screen time and 38 adult outcomes, adjusting for prior screen time, values of most outcomes, and confounders. Most associations were null. Modest evidence was found for links between screen time (continuous) and reduced sense of control, illicit drug use, and allostatic load. High screen time (14 h/week) or more also showed weak associations with lower depression and preventive care use. Because the data predate widespread internet use, the findings help establish a baseline for the long-term effects of non-internet screen activities, which appeared to behave had limited impact on adult health and well-being. en-copyright= kn-copyright= en-aut-name=de la Rosa Fernández-PachecoPedro Antonio en-aut-sei=de la Rosa Fernández-Pacheco en-aut-mei=Pedro Antonio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WilkinsonRenae en-aut-sei=Wilkinson en-aut-mei=Renae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=CowdenRichard G. en-aut-sei=Cowden en-aut-mei=Richard G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChenYing en-aut-sei=Chen en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CaseBrendan en-aut-sei=Case en-aut-mei=Brendan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=VanderWeeleTyler J. en-aut-sei=VanderWeele en-aut-mei=Tyler J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Youth in Transition, Institute for Culture and Society, Universidad de Navarra kn-affil= affil-num=2 en-affil=Human Flourishing Program, Institute for Quantitative Social Science, Harvard University kn-affil= affil-num=3 en-affil=Human Flourishing Program, Institute for Quantitative Social Science, Harvard University kn-affil= affil-num=4 en-affil=Human Flourishing Program, Institute for Quantitative Social Science, Harvard University kn-affil= affil-num=5 en-affil=Human Flourishing Program, Institute for Quantitative Social Science, Harvard University kn-affil= affil-num=6 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Leisure kn-keyword=Leisure en-keyword=Television kn-keyword=Television en-keyword=Outcome-wide epidemiology kn-keyword=Outcome-wide epidemiology en-keyword=Video games kn-keyword=Video games en-keyword=Adolescence kn-keyword=Adolescence en-keyword=Well-being kn-keyword=Well-being END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=2 article-no= start-page=dmm052605 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A genetic model of congenital intestinal atresia implicates Mypt1 in epithelial organisation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Congenital intestinal atresia (IA) is a birth defect characterised by the absence or closure of part of the intestine. Although genetic factors are implicated, mechanistic understanding has been hindered by the lack of suitable animal models. Here, we describe a medaka (Oryzias latipes) mutant, generated by N-ethyl-N-nitrosourea (ENU) mutagenesis, that develops IA during embryogenesis. Positional cloning identified a nonsense mutation in mypt1, encoding myosin phosphatase target subunit 1. Mutant embryos exhibited ectopic accumulation of F-actin and phosphorylated myosin regulatory light chain (Mrlc) in the intestinal epithelium, consistent with disrupted actomyosin regulation. These cytoskeletal abnormalities were accompanied by epithelial disorganisation, without notable alterations in cell proliferation, motility or apoptosis. Inhibition of myh11a, encoding smooth muscle (SM) myosin heavy chain, ameliorated the IA phenotype, whereas blebbistatin treatment completely rescued the defect, suggesting a non-contractile role prior to SM maturation. Together, these findings demonstrate that mypt1 loss disrupts intestinal morphogenesis through actomyosin dysregulation. Given the recent clinical identification of IA associated with MYPT1 variants, this medaka model offers a valuable platform to investigate the developmental and molecular basis of MYPT1-associated IA in humans. en-copyright= kn-copyright= en-aut-name=KobayashiDaisuke en-aut-sei=Kobayashi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UrasakiAkihiro en-aut-sei=Urasaki en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraTetsuaki en-aut-sei=Kimura en-aut-mei=Tetsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AnsaiSatoshi en-aut-sei=Ansai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuoKazuhiko en-aut-sei=Matsuo en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YokoiHayato en-aut-sei=Yokoi en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakashimaShigeo en-aut-sei=Takashima en-aut-mei=Shigeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KitagawaTadao en-aut-sei=Kitagawa en-aut-mei=Tadao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KageTakahiro en-aut-sei=Kage en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaritaTakanori en-aut-sei=Narita en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=JindoTomoko en-aut-sei=Jindo en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KinoshitaMasato en-aut-sei=Kinoshita en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NaruseKiyoshi en-aut-sei=Naruse en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakajimaYoshiro en-aut-sei=Nakajima en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShigetaMasaki en-aut-sei=Shigeta en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SakakiShinichiro en-aut-sei=Sakaki en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=InoueSatoshi en-aut-sei=Inoue en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SabaRie en-aut-sei=Saba en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamadaKei en-aut-sei=Yamada en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YokoyamaTakahiko en-aut-sei=Yokoyama en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=IshikawaYuji en-aut-sei=Ishikawa en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ArakiKazuo en-aut-sei=Araki en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SagaYumiko en-aut-sei=Saga en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TakedaHiroyuki en-aut-sei=Takeda en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YashiroKenta en-aut-sei=Yashiro en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= affil-num=1 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=2 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=3 en-affil=Medical Genome Center, Research Institute, National Center for Geriatrics and Gerontology kn-affil= affil-num=4 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=5 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=6 en-affil=Graduate School of Agricultural Science, Tohoku University kn-affil= affil-num=7 en-affil=Institute for Glyco-core Research (iGCORE)/Life Science Research Centre, Gifu University kn-affil= affil-num=8 en-affil=Program in Environmental Management, Graduate School of Agriculture, Kindai University kn-affil= affil-num=9 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=10 en-affil=Laboratory of Molecular Biology, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University kn-affil= affil-num=11 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=12 en-affil=Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University kn-affil= affil-num=13 en-affil=Laboratory of Bioresources, National Institute for Basic Biology kn-affil= affil-num=14 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=15 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=16 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=17 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=18 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=19 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=20 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=21 en-affil=Research Centre for Radiation Protection, National Institute of Radiological Sciences kn-affil= affil-num=22 en-affil=Research Center for Aquatic Breeding, National Research Institute of Aquaculture, Fisheries Research Agency kn-affil= affil-num=23 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=24 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=25 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= en-keyword=Intestinal atresia kn-keyword=Intestinal atresia en-keyword=Mypt1 kn-keyword=Mypt1 en-keyword=Disease model kn-keyword=Disease model en-keyword=Actomyosin regulation kn-keyword=Actomyosin regulation en-keyword=Intestinal development kn-keyword=Intestinal development END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=3 article-no= start-page=e70044 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Simple Method for RNA-Seq of Manually Isolated Chromatophores in Oryzias Fishes en-subtitle= kn-subtitle= en-abstract= kn-abstract=RNA sequencing (RNA-seq) has become an essential tool for analyzing gene expression and exploring cell type–specific transcriptomes. However, sample preparation and quality control remain challenging, as current approaches typically rely on dissecting tissues containing mixed cell populations or using flow cytometry to isolate fluorescently labeled cells. Here we present a simple and reliable method for RNA-seq of chromatophores (pigment cells) by manually isolating cells based on their natural pigmentation. We analyzed four chromatophore types—melanophores, xanthophores, iridophores, and leucophores—in medaka (Oryzias latipes). Remarkably, as few as 100 cells per type yielded reasonably high-quality transcriptomes sufficient to identify differentially expressed genes (DEGs). Furthermore, this method was successfully applied to a non-model medaka species, O. woworae, which shares the same four chromatophore types. Our approach enables efficient, low-cost, and cross-species transcriptome analysis of chromatophores without requiring transgenic markers or flow cytometry. en-copyright= kn-copyright= en-aut-name=GodaMakoto en-aut-sei=Goda en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyagiAsuka en-aut-sei=Miyagi en-aut-mei=Asuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugiwakaKeisuke en-aut-sei=Sugiwaka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeMasakatsu en-aut-sei=Watanabe en-aut-mei=Masakatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Bessho‐UeharaManabu en-aut-sei=Bessho‐Uehara en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HibiMasahiko en-aut-sei=Hibi en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyodaAtsushi en-aut-sei=Toyoda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaRieko en-aut-sei=Tanaka en-aut-mei=Rieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MasengiKawilarang W. A. en-aut-sei=Masengi en-aut-mei=Kawilarang W. A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamahiraKazunori en-aut-sei=Yamahira en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AnsaiSatoshi en-aut-sei=Ansai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HashimotoHisashi en-aut-sei=Hashimoto en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Institute of Photonics Medicine, Hamamatsu University School of Medicine kn-affil= affil-num=2 en-affil=Institute of Photonics Medicine, Hamamatsu University School of Medicine kn-affil= affil-num=3 en-affil=Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University kn-affil= affil-num=4 en-affil=Cellular and Structural Physiology Institute (CeSPI) and Graduate School of Pharmaceutical Sciences, Nagoya University kn-affil= affil-num=5 en-affil=Frontier Research Institute for Interdisciplinary Science, Tohoku University kn-affil= affil-num=6 en-affil=Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University kn-affil= affil-num=7 en-affil=Comparative Genomics Laboratory, National Institute of Genetics kn-affil= affil-num=8 en-affil=World Medaka Aquarium, Nagoya Higashiyama Zoo and Botanical Gardens kn-affil= affil-num=9 en-affil=Faculty of Fisheries and Marine Science, Sam Ratulangi University kn-affil= affil-num=10 en-affil=Tropical Biosphere Research Center, University of the Ryukyus kn-affil= affil-num=11 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=12 en-affil=Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=23 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Band-selective plasmonic polaron in thermoelectric semimetal Ta2PdSe6 with ultra-high power factor en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report the electronic structure of the thermoelectric semimetal Ta2PdSe6 with a large thermoelectric power factor and giant Peltier conductivity by means of angle-resolved photoemission spectroscopy (ARPES). The ARPES spectra reveal the coexistence of a sharp hole band with a light electron mass and a broad electron band with a relatively heavy electron mass, which originate from different quasi-one-dimensional (Q1D) chains in Ta2PdSe6. Moreover, the electron band around the Brillouin-zone (BZ) boundary shows a replica structure with respect to the energy originating from plasmonic polarons due to electron-plasmon interactions. The different scattering effects and interactions in each atomic chain lead to asymmetric transport lifetimes of carriers: a large Seebeck coefficient can be realized even in a semimetal. Our findings pave the way for exploring the thermoelectric materials in previously overlooked semimetals and provide a new platform for low-temperature thermoelectric physics, which has been challenging with semiconductors. en-copyright= kn-copyright= en-aut-name=OotsukiDaiki en-aut-sei=Ootsuki en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakanoAkitoshi en-aut-sei=Nakano en-aut-mei=Akitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaruokaUrara en-aut-sei=Maruoka en-aut-mei=Urara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HasegawaTakumi en-aut-sei=Hasegawa en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AritaMasashi en-aut-sei=Arita en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitamuraMiho en-aut-sei=Kitamura en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HoribaKoji en-aut-sei=Horiba en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaTeppei en-aut-sei=Yoshida en-aut-mei=Teppei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TerasakiIchiro en-aut-sei=Terasaki en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Present address: Department of Applied Physics, Nagoya University kn-affil= affil-num=3 en-affil=Present address: Department of Applied Physics, Nagoya University kn-affil= affil-num=4 en-affil=Graduate School of Advanced Science and Engineering, Hiroshima University kn-affil= affil-num=5 en-affil=Research Institute for Synchrotron Radiation Science, Hiroshima University kn-affil= affil-num=6 en-affil=Present address: NanoTerasu Center, National Institutes for Quantum Science and Technology (QST) kn-affil= affil-num=7 en-affil=Present address: NanoTerasu Center, National Institutes for Quantum Science and Technology (QST) kn-affil= affil-num=8 en-affil=Graduate School of Human and Environmental Studies, Kyoto University kn-affil= affil-num=9 en-affil=Present address: Department of Applied Physics, Nagoya University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue= article-no= start-page=101798 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alcohol consumption, smoking, and the implications of their cessations for field carcinogenesis in the esophagus: a 10-year prospective cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Alcohol and tobacco are established carcinogens, which promote field carcinogenesis for esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the long-term effects of alcohol and tobacco cessations, and background mucosal status, on risk for metachronous ESCC (mESCC) after endoscopic resection (ER).
Methods This was a multicentre prospective cohort study of patients with intramucosal ESCC treated by ER. All participants received structured education on cessation, and underwent regular endoscopic surveillance. Patients were stratified by Lugol-voiding lesion (LVL) grade (A: none, B: 1–9, C: ≥10). The impacts of alcohol and smoking cessation on field carcinogenesis were assessed.
Findings Among 331 enrolled patients, the median follow-up was 120 months (range: 1.3–176.9). The cumulative incidences of mESCC were 10.4%, 27.2%, and 61.8% in grades A, B, and C, respectively. An increment of 1 unit (22 g ethanol) of alcohol consumption and higher LVL grade independently increased the risk for mESCC. Alcohol or smoking cessation reduced this risk (hazard ratio [HR] 0.52, 95% confidence interval [CI]: 0.31–0.88; HR 0.44, 95% CI: 0.25–0.78, respectively), and combined cessation had the greatest impact (HR 0.21, 95% CI: 0.07–0.65). Complete cessation, rather than partial reduction, was necessary to achieve meaningful risk reduction.
Interpretation Alcohol and tobacco exposure, and a large number of LVL, are major determinants of mESCC. Complete cessation markedly reduces risk, underscoring the importance of behavioural interventions for secondary prevention of field carcinogenesis after ER. en-copyright= kn-copyright= en-aut-name=KatadaChikatoshi en-aut-sei=Katada en-aut-mei=Chikatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokoyamaTetsuji en-aut-sei=Yokoyama en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanoTomonori en-aut-sei=Yano en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FurueYasuaki en-aut-sei=Furue en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiHaruhisa en-aut-sei=Suzuki en-aut-mei=Haruhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshidoKenji en-aut-sei=Ishido en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoKeiko en-aut-sei=Yamamoto en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanishiHiroyoshi en-aut-sei=Nakanishi en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KoikeTomoyuki en-aut-sei=Koike en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TamaokiMasashi en-aut-sei=Tamaoki en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawataNoboru en-aut-sei=Kawata en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HiraoMotohiro en-aut-sei=Hirao en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OgataTakashi en-aut-sei=Ogata en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KatagiriAtsushi en-aut-sei=Katagiri en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamanouchiTakenori en-aut-sei=Yamanouchi en-aut-mei=Takenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiyokawaHirofumi en-aut-sei=Kiyokawa en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawakuboHirofumi en-aut-sei=Kawakubo en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KonnoMaki en-aut-sei=Konno en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YokoyamaAkira en-aut-sei=Yokoyama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=OhashiShinya en-aut-sei=Ohashi en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=OmoriTai en-aut-sei=Omori en-aut-mei=Tai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=ShimodaTadakazu en-aut-sei=Shimoda en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OchiaiAtsushi en-aut-sei=Ochiai en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=IshikawaHideki en-aut-sei=Ishikawa en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=YokoyamaAkira en-aut-sei=Yokoyama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=MutoManabu en-aut-sei=Muto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= affil-num=1 en-affil=Department of Medical Oncology, Kyoto University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Health Promotion, National Institute of Public Health kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East kn-affil= affil-num=4 en-affil=Department of Endoscopy, Saitama Cancer Center kn-affil= affil-num=5 en-affil=Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=7 en-affil=Division of Endoscopy, Hokkaido University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Ishikawa Prefectural Central Hospital kn-affil= affil-num=9 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Medical Oncology, Kyoto University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Division of Endoscopy, Shizuoka Cancer Center kn-affil= affil-num=12 en-affil=Department of Surgery, NHO Osaka National Hospital kn-affil= affil-num=13 en-affil=Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Gastrointestinal Surgery, Kanagawa Cancer Center kn-affil= affil-num=15 en-affil=Division of Gastroenterology, Department of Medicine, Showa Medical University Hospital kn-affil= affil-num=16 en-affil=Department of Gastroenterology, Kumamoto Regional Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=18 en-affil= kn-affil= affil-num=19 en-affil=Department of Gastroenterology, Tochigi Cancer Center kn-affil= affil-num=20 en-affil=Department of Medical Oncology, Kyoto University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Medical Oncology, Kyoto University Graduate School of Medicine kn-affil= affil-num=22 en-affil=Department of Surgery, Kawasaki Municipal Kawasaki Hospital kn-affil= affil-num=23 en-affil=Department of Diagnostic Pathology, Shizuoka Cancer Center kn-affil= affil-num=24 en-affil=Exploratory Oncology Research and Clinicai Trial Center, National Cancer Center kn-affil= affil-num=25 en-affil=Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine kn-affil= affil-num=26 en-affil=Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center kn-affil= affil-num=27 en-affil=Department of Medical Oncology, Kyoto University Graduate School of Medicine kn-affil= en-keyword=Esophageal squamous cell carcinoma kn-keyword=Esophageal squamous cell carcinoma en-keyword=Field carcinogenesis kn-keyword=Field carcinogenesis en-keyword=Metachronous cancer kn-keyword=Metachronous cancer en-keyword=Alcohol kn-keyword=Alcohol en-keyword=Tobacco kn-keyword=Tobacco en-keyword=Lugol-voiding lesion kn-keyword=Lugol-voiding lesion END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=5 article-no= start-page=2339 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Concentration-Dependent Synergistic Interfacial Interactions Between Multifunctional Acrylate and Silane Coupling Agents in an Organic–Inorganic Nanohybrid Material en-subtitle= kn-subtitle= en-abstract= kn-abstract=Synergistic effects of a multifunctional acrylate and a long-chain silane coupling agent were investigated in an organic–inorganic nanohybrid material. We tested the bond strength of nanohybrid composites treated with experimental primers containing silane coupling agents—3-methacryloxypropyl trimethoxysilane (γ-MPTS) or 8-methacryloxyoctyl trimethoxysilane (8-MOTS)—with or without multifunctional acrylates—trimethylolpropane triacrylate (A-TMPT) or dipentaerythritol hexaacrylate (A-DPH). Shear bond strength was evaluated after 24 h of water storage at 37 °C. Untreated control and silane-only groups exhibited low shear bond strengths (e.g., control: 2.4 ± 2.0 MPa) and failed exclusively at the adhesive interface. While addition of A-TMPT did not significantly improve bond strength, addition of A-DPH produced significantly higher shear bond strengths. Highest strength was achieved with 30% 8-MOTS and A-DPH (22.4 ± 6.1 MPa), followed by 20% γ-MPTS and A-DPH (19.0 ± 7.0 MPa), and A-DPH groups produced cohesive failures. Regardless of the silane used (γ-MPTS or 8-MOTS), incorporating A-DPH in the primer consistently yielded superior bond strengths, indicating a promising strategy for improved adhesion for such nanohybrid systems. These findings provide new insights into optimizing resin–filler interfacial interactions and may contribute to the development of restorative materials with improved long-term clinical durability. en-copyright= kn-copyright= en-aut-name=MaruoYukinori en-aut-sei=Maruo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IrieMasao en-aut-sei=Irie en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KodamaNaoki en-aut-sei=Kodama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshizaneMai en-aut-sei=Yoshizane en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AkiyamaKentaro en-aut-sei=Akiyama en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Prosthodontics, Okayama University kn-affil= affil-num=2 en-affil=Health Research Institute, National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=3 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University kn-affil= affil-num=5 en-affil=Department of Prosthodontics, Okayama University kn-affil= affil-num=6 en-affil=Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=silane coupling kn-keyword=silane coupling en-keyword=multifunctional acrylate kn-keyword=multifunctional acrylate en-keyword=bond strength kn-keyword=bond strength en-keyword=resin kn-keyword=resin END start-ver=1.4 cd-journal=joma no-vol=411 cd-vols= no-issue=1 article-no= start-page=21 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Surgical outcomes and patient selection in nonagenarians with colon cancer: a comparative multi-institutional study of laparoscopic and open approaches en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose The appropriate surgical approach for colon cancer (CC) in nonagenarian patients remains a subject of clinical debate. This study aimed to compare the short-term outcomes of laparoscopic (Lap) versus open (Open) surgery in patients aged ≥ 90 years with resectable colon cancer.
Methods This multi-institutional retrospective cohort study included oldest-old patientswith pathological Stage II/III CC who underwent elective surgery at 15 hospitals between 2011 and 2022. Patients with rectal cancer, Stage 0/I/IV disease, or emergency surgery were excluded. To address selection bias, inverse-probability-weighted regression adjustment and stabilized inverse probability of treatment weighting (sIPTW) were applied. The primary outcome was postoperative complications; secondary outcomes included overall survival (OS).
Results Median age was 92 years in both groups. Before adjustment, the Lap group had a higher proportion of female patients (p = 0.038) and lower ASA scores (p = 0.01). Laparoscopic surgery was associated with a significantly longer operative time (220 vs. 171 min, p = 0.046) but less intraoperative blood loss (10 vs. 78 mL, p < 0.01). Postoperative complication rates were comparable (Lap: 31.8%, Open: 33.8%), while the Lap group had a significantly shorter hospital stay (13 vs. 17 days, p < 0.01). D3 lymph node dissection was more frequently performed in the Lap group (p < 0.01). After sIPTW, overall survival did not differ significantly between groups (p = 0.61).
Conclusion Both laparoscopic and open surgery are feasible options for selected nonagenarians with colon cancer. Laparoscopic surgery may offer benefits in terms of reduced blood loss and shorter hospitalization, despite longer operative times. Careful patient selection considering frailty and comorbidities is essential in determining the most appropriate surgical approach. en-copyright= kn-copyright= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakanagaSatoe en-aut-sei=Takanaga en-aut-mei=Satoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InadaRyo en-aut-sei=Inada en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ToshimaToshiaki en-aut-sei=Toshima en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhtaniTsuyoshi en-aut-sei=Ohtani en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaRyosuke en-aut-sei=Yoshida en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HoriNaoto en-aut-sei=Hori en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShigemitsuKaoru en-aut-sei=Shigemitsu en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamamotoSumiharu en-aut-sei=Yamamoto en-aut-mei=Sumiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KubotaTetsushi en-aut-sei=Kubota en-aut-mei=Tetsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkanoYuka en-aut-sei=Okano en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NobuhisaTetsuji en-aut-sei=Nobuhisa en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TaniguchiFumitaka en-aut-sei=Taniguchi en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IshikawaWataru en-aut-sei=Ishikawa en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsudaTatsuo en-aut-sei=Matsuda en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UmeokaTatsuo en-aut-sei=Umeoka en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=Setouchi Colorectal Neoplasm Registration study group collaborators en-aut-sei=Setouchi Colorectal Neoplasm Registration study group collaborators en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Surgery, Kagawa Rosai Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Saiseikai Okayama Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, Okayama Rosai Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, Tottori Municipal Hospital kn-affil= affil-num=10 en-affil=Department of Surgery, Tsuyama Chuo Hospital kn-affil= affil-num=11 en-affil=Department of Surgery, Okayama City Hospital kn-affil= affil-num=12 en-affil=Department of Surgery, Kobe Red Cross Hospital kn-affil= affil-num=13 en-affil=Department of Surgery, Onomichi City Hospital kn-affil= affil-num=14 en-affil=Department of Surgery, Himeji Red Cross Hospital kn-affil= affil-num=15 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=16 en-affil=Department of Surgery, Fukuyama City Hospital kn-affil= affil-num=17 en-affil=Department of Surgery, Matsuda Hospital kn-affil= affil-num=18 en-affil=Department of Surgery, Matsuyama City Hospital kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil= kn-affil= en-keyword=Oldest-old patients kn-keyword=Oldest-old patients en-keyword=Colon cancer kn-keyword=Colon cancer en-keyword=Laparoscopic surgery kn-keyword=Laparoscopic surgery en-keyword=Surgical outcome kn-keyword=Surgical outcome en-keyword=Overall survival kn-keyword=Overall survival END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=1 article-no= start-page=e70089 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lifestyle Factors and Current Alcohol Consumption Among Japanese Adolescents During the COVID-19 Pandemic: A Nationwide Cross-Sectional Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The COVID-19 pandemic may have influenced drinking behaviors in minors by disrupting daily routines and increasing psychosocial stress, although alcohol use among Japanese adolescents has declined in recent years. We aimed to clarify the relationships between current alcohol consumption and lifestyle factors during the COVID-19 pandemic based on a nationwide cross-sectional survey.
Methods: This cross-sectional study analyzed data from the 2021 Lifestyle Survey of Adolescents, a nationwide survey conducted in Japan during the COVID-19 pandemic. A total of 15 549 junior and senior high school students (7645 boys and 7904 girls) were included. Current alcohol consumption was defined as drinking on at least 1 day in the past 30 days. Multivariable logistic regression analyses were used to examine associations between current alcohol consumption and lifestyle factors, including irregular sleep patterns, irregular dietary habits, and increased screen time. Sex-stratified analyses and interaction tests were also performed.
Results: The overall prevalence of current alcohol consumption was 2.1%, with slightly higher rates among boys (2.2%) than girls (2.0%). Current alcohol consumption was significantly associated with irregular sleep patterns (odds ratio [OR] = 1.51; 95% confidence interval [CI], 1.17–1.95) and irregular dietary habits (OR = 1.68; 95% CI, 1.18–2.40). An association with increased screen time was also observed (OR = 1.29; 95% CI, 1.00–1.69), particularly among boys. A significant interaction by sex was detected for irregular sleep patterns (p for interaction = 0.013).
Conclusions: Alcohol consumption among Japanese adolescents was associated with irregular sleep and dietary habits and, among boys, with increased screen time. These findings highlight the importance of promoting regular routines and addressing lifestyle-related risks to prevent current alcohol consumption among adolescents during public health crises. en-copyright= kn-copyright= en-aut-name=NishiwakiMasatake en-aut-sei=Nishiwaki en-aut-mei=Masatake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KandaHideyuki en-aut-sei=Kanda en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaKeita en-aut-sei=Yoshida en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KinjoAya en-aut-sei=Kinjo en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuwabaraYuki en-aut-sei=Kuwabara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimHongja en-aut-sei=Kim en-aut-mei=Hongja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ImamotoAya en-aut-sei=Imamoto en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshimotoHisashi en-aut-sei=Yoshimoto en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoTeruna en-aut-sei=Ito en-aut-mei=Teruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KasugaHideaki en-aut-sei=Kasuga en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MinobeRuriko en-aut-sei=Minobe en-aut-mei=Ruriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaesatoHitoshi en-aut-sei=Maesato en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=JikeMaki en-aut-sei=Jike en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OtsukaYuichiro en-aut-sei=Otsuka en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ItaniOsamu en-aut-sei=Itani en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KaneitaYoshitaka en-aut-sei=Kaneita en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HiguchiSusumu en-aut-sei=Higuchi en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OsakiYoneatsu en-aut-sei=Osaki en-aut-mei=Yoneatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=6 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=7 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=8 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=9 en-affil=Department of Family Medicine, General Practice and Community Health, Institute of Medicine, University of Tsukuba kn-affil= affil-num=10 en-affil=Department of Food and Nutrition, Koriyama Women's University kn-affil= affil-num=11 en-affil=Department of Hygiene and Preventive Medicine, Fukushima Medical University kn-affil= affil-num=12 en-affil=National Institute of Alcoholism, Kurihama National Hospital kn-affil= affil-num=13 en-affil=National Institute of Alcoholism, Kurihama National Hospital kn-affil= affil-num=14 en-affil=Department of Food Science and Nutrition, Faculty of Life and Environmental Science, Showa Women's University kn-affil= affil-num=15 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=16 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=17 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=18 en-affil=National Institute of Alcoholism, Kurihama National Hospital kn-affil= affil-num=19 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= en-keyword=adolescent kn-keyword=adolescent en-keyword=alcohol drinking kn-keyword=alcohol drinking en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=Japan kn-keyword=Japan en-keyword=lifestyle kn-keyword=lifestyle END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=50 article-no= start-page=e06926 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Collagen Signaling via DDR1 Exacerbates Barriers to Macromolecular Drug Delivery in a 3D Model of Pancreatic Cancer Fibrosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fibrosis is a significant barrier to drug delivery in pancreatic ductal adenocarcinoma (PDAC) and contributes to its dismal prognosis. Pancreatic stellate cells (PSCs) drive fibrosis by excessively secreting extracellular matrix proteins such as collagen I. Collagen I is thought to physically obstruct the delivery of macromolecules, such as albumin, antibodies, and nanomedicines. Apart from its structural role, collagen signals through dedicated cell surface receptors, such as the discoidin domain receptors (DDR) 1/2. However, whether and how collagen signaling contributes to fibrotic barrier generation remains uncharacterized. Here, a 3D culture model of PDAC fibrosis constructed from patient PSCs is used to assess the contribution of DDR1/2-mediated collagen signaling. DDR1/2 inhibition diminishes collagen I expression in PSCs to enhance macromolecular delivery. Moreover, MEK inhibitors exacerbate the fibrotic barrier by up-regulating collagen I, an effect reversed by inhibiting DDR1/2. Through isoform-specific targeting, inhibiting DDR1, but not DDR2, is shown to be effective. Downstream of DDR, the involvement of the PI3K/AKT/mTOR pathway is demonstrated, particularly alternative mTOR complexes involving MEAK7 and GIT1. Altogether, the results show in vitro that DDR1-mediated collagen signaling exacerbates the fibrotic barrier and may be targeted to enhance macromolecular drug delivery in PDAC. en-copyright= kn-copyright= en-aut-name=OhiraMayu en-aut-sei=Ohira en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitamuraMoe en-aut-sei=Kitamura en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IwasakiHiroyo en-aut-sei=Iwasaki en-aut-mei=Hiroyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Ohta‐OkanoHaruko en-aut-sei=Ohta‐Okano en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujiiHiyori en-aut-sei=Tsujii en-aut-mei=Hiyori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraReika en-aut-sei=Nakamura en-aut-mei=Reika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakazawaTakuya en-aut-sei=Nakazawa en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishiguchiAkihiro en-aut-sei=Nishiguchi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoMasaya en-aut-sei=Yamamoto en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OsadaKensuke en-aut-sei=Osada en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=CabralHoracio en-aut-sei=Cabral en-aut-mei=Horacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MasamuneAtsushi en-aut-sei=Masamune en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KanoMitsunobu R. en-aut-sei=Kano en-aut-mei=Mitsunobu R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaHiroyoshi Y. en-aut-sei=Tanaka en-aut-mei=Hiroyoshi Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Biomaterials Field, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science kn-affil= affil-num=9 en-affil=Department of Materials Processing, Graduate School of Engineering, Tohoku University kn-affil= affil-num=10 en-affil=Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Sciences and Technology (QST) kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Bioengineering, Graduate School of Engineering, The University of Tokyo kn-affil= affil-num=13 en-affil=Division of Gastroenterology, Graduate School of Medicine, Tohoku University kn-affil= affil-num=14 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=15 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=collagen kn-keyword=collagen en-keyword=fibrosis kn-keyword=fibrosis en-keyword=nanomedicine kn-keyword=nanomedicine en-keyword=pancreatic cancer kn-keyword=pancreatic cancer en-keyword=pancreatic stellate cell kn-keyword=pancreatic stellate cell END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=1 article-no= start-page=120 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of clinical practices during the transitional and young adult phases between patients with oligoarticular/polyarticular juvenile idiopathic arthritis and those with rheumatoid arthritis in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Juvenile idiopathic arthritis (JIA) is a chronic inflammatory condition that frequently persists into adulthood, posing long-term challenges in disease control and quality of life. However, clinical management during the transitional and young adult phases remains insufficiently characterized, especially in comparison with adult-onset rheumatoid arthritis (RA). This study aimed to compare disease activity, medication use, and treatment practices between patients with oligoarticular/polyarticular JIA and those with RA, focusing on individuals aged 16–30 years.
Methods Data were derived from two nationwide multicenter databases in Japan—NinJa (National Database of Rheumatic Diseases in Japan) for RA and CoNinJa (a pediatric counterpart of NinJa) for JIA. A total of 176 JIA and 152 RA patients, all aged 16–30 years, were analyzed. Clinical parameters, disease activity indices, and medication profiles were compared using the Mann–Whitney U test and Fisher’s exact test.
Results Compared to RA patients, JIA patients demonstrated significantly lower disease activity (median SDAI 0.6 vs. 2.4) and higher remission rates, particularly Boolean remission (70% vs. 44%) (p < 0.001). MTX usage was less frequent in JIA (49% vs. 68%, p < 0.001), whereas biologic use was notably more common (69% vs. 38%, p < 0.001), with 31% involving off-label prescriptions. Among patients in CDAI remission, biologic monotherapy was observed more frequently in JIA (29% vs. 7%, p < 0.001). Discontinuation of MTX was most commonly attributed to disease improvement (58%) or gastrointestinal intolerance (nausea, 29%). Subcutaneous tocilizumab, though unapproved for JIA in Japan, had the lowest discontinuation rate (4%), suggesting favorable tolerability.
Conclusions Despite an overlap in age, patients with JIA and RA exhibit distinct disease characteristics and therapeutic patterns. These differences underscore the need to expand approved treatment options for JIA, promote equitable access to biologics, and strengthen transitional care frameworks. Further research is warranted to explore long-term outcomes, reproductive health considerations, and socioeconomic barriers that influence treatment continuity in young adults with childhood-onset arthritis. en-copyright= kn-copyright= en-aut-name=MoriSho en-aut-sei=Mori en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShabanaKosuke en-aut-sei=Shabana en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuiToshihiro en-aut-sei=Matsui en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NozawaTomo en-aut-sei=Nozawa en-aut-mei=Tomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugitaYuko en-aut-sei=Sugita en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TomiitaMinako en-aut-sei=Tomiita en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakagishiYasuo en-aut-sei=Nakagishi en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamasakiYuichi en-aut-sei=Yamasaki en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UmebayashiHiroaki en-aut-sei=Umebayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwataNaomi en-aut-sei=Iwata en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YasumuraJunko en-aut-sei=Yasumura en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WakiguchiHiroyuki en-aut-sei=Wakiguchi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamamotoTakeshi en-aut-sei=Yamamoto en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakezakiShunichiro en-aut-sei=Takezaki en-aut-mei=Shunichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OkuraYuka en-aut-sei=Okura en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YokoyamaTadafumi en-aut-sei=Yokoyama en-aut-mei=Tadafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ShimizuMasaki en-aut-sei=Shimizu en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HirayamaMasahiro en-aut-sei=Hirayama en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TohmaShigeto en-aut-sei=Tohma en-aut-mei=Shigeto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=OkamotoNami en-aut-sei=Okamoto en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MoriMasaaki en-aut-sei=Mori en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine kn-affil= affil-num=2 en-affil=Department of Pediatrics, Osaka Medical and Pharmaceutical University kn-affil= affil-num=3 en-affil=Department of Rheumatology Research, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, Graduate School of Medicine, Yokohama City University kn-affil= affil-num=5 en-affil=Department of Pediatrics, Osaka Medical and Pharmaceutical University kn-affil= affil-num=6 en-affil=Department of Allergy and Rheumatology, Chiba Children’s Hospital kn-affil= affil-num=7 en-affil=Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Children’s Hospital kn-affil= affil-num=8 en-affil=Department of Pediatrics, Kagoshima University Hospital kn-affil= affil-num=9 en-affil=Department of General Pediatrics, Miyagi Children’s Hospital kn-affil= affil-num=10 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Infection and Immunology, Allergy and Immunology Center, Aichi Children’s Health and Medical Center kn-affil= affil-num=12 en-affil=Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences kn-affil= affil-num=13 en-affil=Department of Pediatrics, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Pediatrics, Chiba University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Pediatrics, Faculty of Medicinea and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=16 en-affil=Center for Pediatric Allergy and Rheumatology, KKR Sapporo Medical Center kn-affil= affil-num=17 en-affil=Department of Pediatrics, Kanazawa University kn-affil= affil-num=18 en-affil=Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= affil-num=19 en-affil=Department of Pediatrics, Mie University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Rheumatology, National Hospital Organization Tokyo National Hospital kn-affil= affil-num=21 en-affil=Department of Pediatrics, Osaka Medical and Pharmaceutical University kn-affil= affil-num=22 en-affil=Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine kn-affil= en-keyword=Juvenile idiopathic arthritis kn-keyword=Juvenile idiopathic arthritis en-keyword=Rheumatoid arthritis kn-keyword=Rheumatoid arthritis en-keyword=Disease activity kn-keyword=Disease activity en-keyword=Biologics kn-keyword=Biologics en-keyword=Methotrexate kn-keyword=Methotrexate END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=11 article-no= start-page=e2543107 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trastuzumab Deruxtecan for ERBB2-Mutant Metastatic Non–Small Cell Lung Cancer With or Without Brain Metastases: A Secondary Analysis of Randomized Clinical Trials en-subtitle= kn-subtitle= en-abstract= kn-abstract=Importance Brain metastases reduce overall survival rates of patients with non–small cell lung cancer (NSCLC); patients with epidermal growth factor receptor 2 (ERBB2 [formerly HER2])–mutant NSCLC are more likely to have baseline brain metastases. Trastuzumab deruxtecan (T-DXd) is an approved ERBB2-directed treatment for previously treated unresectable or metastatic ERBB2-mutant NSCLC.
Objective To assess the clinical effectiveness and safety of T-DXd 5.4 mg/kg and 6.4 mg/kg doses in patients with previously treated ERBB2-mutant metastatic NSCLC with or without untreated or previously treated stable brain metastases.
Design, Setting, and Participants This post hoc secondary analysis pooled patients from the DESTINY-Lung01 (data cutoff date: December 3, 2021) and DESTINY-Lung02 (data cutoff date: December 23, 2022) clinical trials by T-DXd dose (5.4 mg/kg and 6.4 mg/kg). DESTINY-Lung01 was a multicenter, open-label, 2-cohort, nonrandomized phase 2 study, while DESTINY-Lung02 was a dose-blinded, multicenter, 2-cohort, randomized phase 2 study. Participants had a previously treated ERBB2-mutant metastatic NSCLC with or without untreated or previously treated stable brain metastases at baseline. All statistical analyses were performed from April 2023 to October 2024.
Intervention Patients received a T-DXd dose of either 5.4 mg/kg or 6.4 mg/kg intravenously every 3 weeks.
Main Outcome and Measure Systemic and intracranial effectiveness by blinded independent central review using RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1, sites of progression, and safety.
Results This analysis included 102 patients in the T-DXd 5.4-mg/kg dose group (65 females [64%]; median [range] age, 57.5 [37.0-83.0] years and 59.5 [30.0-79.0] years in patients with and without brain metastases, respectively) and 141 patients in the T-DXd 6.4-mg/kg dose group (94 females [67%]; median [range] age, 62.5 [29.0-88.0] years and 59.0 [27.0-83.0] years in patients with and without brain metastases, respectively). In each group, 31% (32 of 102) and 38% (54 of 141) of patients, respectively, had baseline brain metastases and 53% (17 of 32) and 44% (24 of 54), respectively, received prior brain metastasis treatment. In patients with and without brain metastases, systemic confirmed objective response rates (ORRs) were 47% (15 of 32; 95% CI, 29%-65%) and 50% (35 of 70; 95% CI, 38%-62%), respectively, with the T-DXd 5.4-mg/kg dose, and 50% (27 of 54; 95% CI, 36%-64%) and 59% (51 of 87; 95% CI, 48%-69%) with the T-DXd 6.4-mg/kg dose. Median progression-free survival was 7.1 (95% CI, 5.5-9.7) months in the T-DXd 5.4-mg/kg dose group and 7.1 (95% CI, 4.5-9.6) months in the T-DXd 6.4-mg/kg dose group of patients with baseline brain metastases. Among patients with measurable baseline brain metastases, intracranial confirmed ORRs were 50% (7 of 14; 95% CI, 23%-77%) with the T-DXd 5.4-mg/kg dose and 30% (9 of 30; 95% CI, 15%-49%) with the T-DXd 6.4-mg/kg dose. At both doses, the safety profile of T-DXd was generally manageable, regardless of baseline brain metastases, favoring the T-DXd 5.4 mg/kg dose.
Conclusions and Relevance In this secondary analysis, T-DXd at the approved dose of 5.4 mg/kg showed antitumor activity in patients with previously treated ERBB2-mutant metastatic NSCLC with or without brain metastases. This finding supports T-DXd 5.4 mg/kg use in this population. en-copyright= kn-copyright= en-aut-name=JännePasi A. en-aut-sei=Jänne en-aut-mei=Pasi A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PlanchardDavid en-aut-sei=Planchard en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GotoKoichi en-aut-sei=Goto en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SmitEgbert F. en-aut-sei=Smit en-aut-mei=Egbert F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=de LangenAdrianus Johannes en-aut-sei=de Langen en-aut-mei=Adrianus Johannes kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GotoYasushi en-aut-sei=Goto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=PérolMaurice en-aut-sei=Pérol en-aut-mei=Maurice kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FelipEnriqueta en-aut-sei=Felip en-aut-mei=Enriqueta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayashiHidetoshi en-aut-sei=Hayashi en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakagawaKazuhiko en-aut-sei=Nakagawa en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShimizuJunichi en-aut-sei=Shimizu en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NagasakaMisako en-aut-sei=Nagasaka en-aut-mei=Misako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=PereiraKaline en-aut-sei=Pereira en-aut-mei=Kaline kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TaguchiAyumi en-aut-sei=Taguchi en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AliAhmed en-aut-sei=Ali en-aut-mei=Ahmed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KarnoubMaha en-aut-sei=Karnoub en-aut-mei=Maha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YonemochiRie en-aut-sei=Yonemochi en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=LeungDavid en-aut-sei=Leung en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=LiBob T. en-aut-sei=Li en-aut-mei=Bob T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute kn-affil= affil-num=2 en-affil=Department of Medical Oncology, Thoracic Cancer Group, Gustave Roussy, Medical Oncology kn-affil= affil-num=3 en-affil=Department of Thoracic Oncology, Nation Cancer Center Hospital East kn-affil= affil-num=4 en-affil=Department of Pulmonary Diseases, Leiden University Medical Center kn-affil= affil-num=5 en-affil=Department of Thoracic Oncology, Netherlands Cancer Institute kn-affil= affil-num=6 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=7 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Medical Oncology, Centre Léon Bérard kn-affil= affil-num=10 en-affil=Department of Medical Oncology, Vall d’Hebron University and Vall d’Hebron Institute of Oncology kn-affil= affil-num=11 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=12 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=13 en-affil=Department of Thoracic Oncology, Aichi Cancer Center kn-affil= affil-num=14 en-affil=Division of Hematology-Oncology, Department of Medicine, University of California Irvine kn-affil= affil-num=15 en-affil=Daiichi Sankyo Inc kn-affil= affil-num=16 en-affil=Daiichi Sankyo Co Ltd kn-affil= affil-num=17 en-affil=Daiichi Sankyo Europe GmbH kn-affil= affil-num=18 en-affil=Daiichi Sankyo Inc kn-affil= affil-num=19 en-affil=Daiichi Sankyo Inc kn-affil= affil-num=20 en-affil=Daiichi Sankyo Inc kn-affil= affil-num=21 en-affil=Thoracic Oncology and Early Drug Development Service, Global Research Program, Memorial Sloan Kettering Cancer Center kn-affil= END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=12 article-no= start-page=1814 end-page=1828 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Final Analysis Results and Patient-Reported Outcomes From DESTINY-Lung02—A Dose-Blinded, Randomized, Phase 2 Study of Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic NSCLC en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Trastuzumab deruxtecan (T-DXd) demonstrated strong and durable responses in patients with previously treated HER2 (ERBB2) mutant (HER2m) metastatic NSCLC (mNSCLC) in the DESTINY-Lung02 primary analysis (December 23, 2022, data cutoff). This final analysis evaluated T-DXd efficacy and safety after 8 additional months of follow-up, including clinically relevant subgroups and patient-reported outcomes.
Methods: DESTINY-Lung02 was a randomized, dose-blinded, multicenter, phase 2 trial. Patients with previously treated HER2m mNSCLC were randomized 2:1 to receive T-DXd 5.4 or 6.4 mg/kg once every 3 weeks. Primary end point was confirmed objective response rate by blinded independent central review.
Results: As of August 25, 2023, 102 and 50 patients had received T-DXd 5.4 or 6.4 mg/kg, respectively. Median follow-up (Q1–Q3) was 15.8 (8.2–20.7) months and 16.5 (9.4–20.8) months, respectively. Confirmed objective response rate (95% confidence interval) was 50.0% (51/102; 39.9%–60.1%) and 56.0% (28/50; 41.3%–70.0%), respectively. Safety profile was acceptable and generally manageable. Accordingly, median treatment duration (Q1–Q3) was 7.7 (3.7–14.4) months and 8.3 (2.8–13.1) months; drug-related grade 3 or higher treatment-emergent adverse events occurred in 39.6% (40/101) and 60.0% (30/50), with nausea most common (67.3% [68/101], 82.0% [41/50]). Adjudicated drug-related interstitial lung disease occurred in 14.9% (15/101) and 32.0% (16/50), mostly grade 1 or 2 with one grade 5 in each arm. Health-related quality of life was preserved for the duration of T-DXd treatment while sample size was sufficient for analysis, with no adverse effects on health-related quality of life observed at either dose.
Conclusions: T-DXd demonstrated strong and durable responses at both doses, with no clinically significant changes in toxicity. The approved 5.4-mg/kg dose demonstrated a more favorable benefit-risk profile, including lower adjudicated drug-related interstitial lung disease incidence.
ClinicalTrials.gov identifier: NCT04644237 en-copyright= kn-copyright= en-aut-name=JännePasi A. en-aut-sei=Jänne en-aut-mei=Pasi A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GotoYasushi en-aut-sei=Goto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimSang-We en-aut-sei=Kim en-aut-mei=Sang-We kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=PlanchardDavid en-aut-sei=Planchard en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AhnMyung-Ju en-aut-sei=Ahn en-aut-mei=Myung-Ju kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SmitEgbert en-aut-sei=Smit en-aut-mei=Egbert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Johannes de LangenAdrianus en-aut-sei=Johannes de Langen en-aut-mei=Adrianus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=PérolMaurice en-aut-sei=Pérol en-aut-mei=Maurice kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=Pons-TostivintElvire en-aut-sei=Pons-Tostivint en-aut-mei=Elvire kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NovelloSilvia en-aut-sei=Novello en-aut-mei=Silvia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HayashiHidetoshi en-aut-sei=Hayashi en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShimizuJunichi en-aut-sei=Shimizu en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KimDong-Wan en-aut-sei=Kim en-aut-mei=Dong-Wan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=PereiraKaline en-aut-sei=Pereira en-aut-mei=Kaline kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ChengFu-Chih en-aut-sei=Cheng en-aut-mei=Fu-Chih kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TaguchiAyumi en-aut-sei=Taguchi en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ChengYingkai en-aut-sei=Cheng en-aut-mei=Yingkai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=DuntonKyle en-aut-sei=Dunton en-aut-mei=Kyle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AliAhmed en-aut-sei=Ali en-aut-mei=Ahmed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=GotoKoichi en-aut-sei=Goto en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute kn-affil= affil-num=2 en-affil=Department of Thoracic Oncology, National Cancer Central Hospital kn-affil= affil-num=3 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Oncology Department, Asan Medical Center, Seoul, and University of Ulsan College of Medicine, Ulsan kn-affil= affil-num=6 en-affil=Department of Medical Oncology, Thoracic Cancer Group, Gustave Roussy, and Faculty of Medicine, Paris-Saclay University kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Samsung Medical Center Sungkyunkwan, and University School of Medicine kn-affil= affil-num=8 en-affil=Department of Pulmonary Diseases, Leiden University Medical Center kn-affil= affil-num=9 en-affil=Department of Thoracic Oncology, Netherlands Cancer Institute kn-affil= affil-num=10 en-affil=Department of Medical Oncology, Léon Berard Centre kn-affil= affil-num=11 en-affil=Centre Hospitalier Universitaire Nantes, Nantes University kn-affil= affil-num=12 en-affil=Department of Oncology, University of Turin, Turin, and Azienda Ospedaliero-Universitaria San Luigi Gonzaga kn-affil= affil-num=13 en-affil=Department of Medical Oncology, Kindai University Hospital kn-affil= affil-num=14 en-affil=Department of Thoracic Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=15 en-affil=Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital kn-affil= affil-num=16 en-affil=Daiichi Sankyo kn-affil= affil-num=17 en-affil=Daiichi Sankyo kn-affil= affil-num=18 en-affil=Daiichi Sankyo kn-affil= affil-num=19 en-affil=Daiichi Sankyo kn-affil= affil-num=20 en-affil=Daiichi Sankyo UK kn-affil= affil-num=21 en-affil=Daiichi Sankyo Europe GmbH kn-affil= affil-num=22 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital East kn-affil= en-keyword=HER2-directed therapy kn-keyword=HER2-directed therapy en-keyword=HER2-mutant kn-keyword=HER2-mutant en-keyword=HER2-targeted kn-keyword=HER2-targeted en-keyword=Non–small cell lung cancer kn-keyword=Non–small cell lung cancer en-keyword=Trastuzumab deruxtecan kn-keyword=Trastuzumab deruxtecan END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=sr.2024-0099 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Qualification Examination for Specialists and Instructors in the Japanese Society of Neuroendovascular Therapy: History and Current Status en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neuroendovascular therapy is a key treatment for cerebrovascular disorders, driven by advancements in devices and techniques. The Japanese Society for Neuroendovascular Therapy (JSNET) established a certification system in 1997 to ensure operator competence and minimize complications, with the first examination in 2002. JSNET offers 2 main certifications: specialist and instructor. Specialists perform basic procedures, while instructors lead in practice, education, and research. In 2020, the mechanical thrombectomy practitioner qualification was added to promote mechanical thrombectomy. Applicants must have a JSNET membership, relevant certifications, training, and documented experience. The certification process includes rigorous written and practical examinations that now employ non-fluoroscopic models. Certification renewal every 5 years requires conference participation and a continuing education program. Public awareness and integration into stroke center designations have grown. Over 2200 specialists, including more than 500 instructors, have been certified, significantly advancing neuroendovascular therapy in Japan. JSNET aims to continue improving certification and education to maintain high standards. en-copyright= kn-copyright= en-aut-name=YoshimuraShinichi en-aut-sei=Yoshimura en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugiuKenji en-aut-sei=Sugiu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirohataMasaru en-aut-sei=Hirohata en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EnomotoYukiko en-aut-sei=Enomoto en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImamuraHirotoshi en-aut-sei=Imamura en-aut-mei=Hirotoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsurutaWataro en-aut-sei=Tsuruta en-aut-mei=Wataro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujinakaToshiyuki en-aut-sei=Fujinaka en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HasegawaHitoshi en-aut-sei=Hasegawa en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HigashiToshio en-aut-sei=Higashi en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IzumiTakashi en-aut-sei=Izumi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KiyosueHiro en-aut-sei=Kiyosue en-aut-mei=Hiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsumotoYasushi en-aut-sei=Matsumoto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OishiHidenori en-aut-sei=Oishi en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SatowTetsu en-aut-sei=Satow en-aut-mei=Tetsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaMichihiro en-aut-sei=Tanaka en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TsumotoTomoyuki en-aut-sei=Tsumoto en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamagamiHiroshi en-aut-sei=Yamagami en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IshiiAkira en-aut-sei=Ishii en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MatsumaruYuji en-aut-sei=Matsumaru en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MiyachiShigeru en-aut-sei=Miyachi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Neurosurgery, Hyogo Medical University kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Neurosurgery, Kurume Medical University kn-affil= affil-num=4 en-affil=Department of Neurosurgery, Gifu University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Neurosurgery, National Cerebral and Cardiovascular Center kn-affil= affil-num=6 en-affil=Department of Endovascular Neurosurgery, Toranomon Hospital kn-affil= affil-num=7 en-affil=Department of Neurosurgery, National Hospital Organization Osaka National Hospital kn-affil= affil-num=8 en-affil=Department of Neurosurgery, Brain Research Institute, Niigata University kn-affil= affil-num=9 en-affil=Department of Neurosurgery, Fukuoka University Chikushi Hospital kn-affil= affil-num=10 en-affil=Department of Neurosurgery, Nagoya University of Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Diagnostic Radiology, Kumamoto University Faculty of Life Sciences kn-affil= affil-num=12 en-affil=Division of Development and Discovery of Interventional Therapy, Tohoku University Hospital kn-affil= affil-num=13 en-affil=Oishi Neurosurgery Clinic, and Department of Neurosurgery, The Jikei University School of Medicine kn-affil= affil-num=14 en-affil=Department of Neurosurgery/Stroke Center, Kindai University Hospital kn-affil= affil-num=15 en-affil=Department of Neurosurgery and Neuroendovascular Surgery, Kameda Neurocenter, Kameda Medical Center kn-affil= affil-num=16 en-affil=Department of Neurosurgery, Showa University Fujigaoka Hospital kn-affil= affil-num=17 en-affil=Division of Stroke Prevention and Treatment, Institute of Medicine, University of Tsukuba kn-affil= affil-num=18 en-affil=Department of Neurosurgery, Juntendo University Faculty of Medicine kn-affil= affil-num=19 en-affil=Department of Neurosurgery, Institute of Medicine, University of Tsukuba kn-affil= affil-num=20 en-affil=Department of Neurological Surgery, Aichi Medical Univeristy kn-affil= en-keyword=neuroendovascular therapy kn-keyword=neuroendovascular therapy en-keyword=specialist certification kn-keyword=specialist certification en-keyword=Japanese Society for Neuroendovascular Therapy (JSNET) kn-keyword=Japanese Society for Neuroendovascular Therapy (JSNET) en-keyword=mechanical thrombectomy kn-keyword=mechanical thrombectomy END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260213 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Distinct associations of blood pressure phenotypes with subclinical cerebrovascular disease and coronary artery calcification in Japanese men en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hypertension, encompassing white-coat hypertension (WCH), masked hypertension (MH), and sustained hypertension (SH), is an established risk factor for cardiovascular diseases (CVDs), including atherosclerosis. However, among the general population, findings on which target organ is affected by the different phenotypes of hypertension remain unclear. In this community-based observational study of Shiga Epidemiological Study of Subclinical Atherosclerosis, 740 Japanese men underwent brain magnetic resonance imaging to assess the presence of lacunar infarction, white-matter hyperintensities, microbleeds, and intracranial artery stenosis (ICAS) between 2012 and 2015. They also underwent office blood pressure (BP) measurements, home BP monitoring for at least five consecutive days, and coronary artery calcification (CAC) assessments between 2010 and 2014. The final analysis included 686 participants without a history of CVDs. Of the 686 participants, the mean age ( ± SD) was 68.0 ( ± 8.3) years, and 39.3% were taking antihypertensive medication. In multivariable-adjusted models, each of WCH, MH, and SH was significantly associated with a higher risk of microbleeds compared to normotension. However, the association of WCH with microbleeds was evident only among those on antihypertensive medication (adjusted odds ratio [OR] 6.75 [95% CI 1.83–24.86]) and absent in those not on such medication (adjusted OR 1.20 [95% CI 0.31–4.73]). SH was associated with lacunar infarction, ICAS, and CAC. Among Japanese men, WCH, MH, SH were associated with subclinical cerebrovascular diseases, whereas only SH was associated with CAC. Moreover, any elevated BP phenotype increased the risk of microbleeds. Our findings suggest that different hypertension phenotypes distinctly affect target organs, particularly the brain and heart. en-copyright= kn-copyright= en-aut-name=BayaraaNomin en-aut-sei=Bayaraa en-aut-mei=Nomin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YanoYuichiro en-aut-sei=Yano en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KadotaAya en-aut-sei=Kadota en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AzaharNazar Mohd en-aut-sei=Azahar en-aut-mei=Nazar Mohd kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=PhapTran Ngoc Hoang en-aut-sei=Phap en-aut-mei=Tran Ngoc Hoang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KondoKeiko en-aut-sei=Kondo en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ToriiSayuki en-aut-sei=Torii en-aut-mei=Sayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiyoshiAkira en-aut-sei=Fujiyoshi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhkuboTakayoshi en-aut-sei=Ohkubo en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShiinoAkihiko en-aut-sei=Shiino en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NozakiKazuhiko en-aut-sei=Nozaki en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MiuraKatsuyuki en-aut-sei=Miura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=2 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=3 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=4 en-affil= kn-affil= affil-num=5 en-affil=National Institutes of Biomedical Innovation, Health and Nutrition kn-affil= affil-num=6 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=8 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=9 en-affil=Department of Hygiene, School of Medicine, Wakayama Medical University kn-affil= affil-num=10 en-affil=Department of Hygiene and Public Health, Teikyo University School of Medicine kn-affil= affil-num=11 en-affil=Molecular Neuroscience Research Center, Shiga University of Medical Science kn-affil= affil-num=12 en-affil=Department of Neurosurgery, Shiga University of Medical Science kn-affil= affil-num=13 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= en-keyword=Blood pressure phenotypes kn-keyword=Blood pressure phenotypes en-keyword=Morning hypertension kn-keyword=Morning hypertension en-keyword=Home blood pressure kn-keyword=Home blood pressure en-keyword=Subclinical cerebrovascular disease kn-keyword=Subclinical cerebrovascular disease en-keyword=Coronary artery calcification kn-keyword=Coronary artery calcification END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=1 article-no= start-page=146 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250719 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Safety and feasibility of D3 lymph node dissection in oldest-old patients undergoing colorectal cancer surgery: a multi-institutional, retrospective analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Colorectal cancer (CRC) is a significant health burden, with lymph node dissection (LND) playing a critical role in staging and guiding treatment. However, the optimal extent of LND for the oldest-old population (aged ≥ 90 years) remains undefined because of insufficient targeted clinical data. This study aimed to compare the short-term outcomes of D3 versus non-D3 LND in Stage II–III CRC in oldest-old patients.
Methods This retrospective cohort study utilized data from the Setouchi Colorectal Neoplasm Registration database, including 282 oldest-old patients with CRC treated between 2011 and 2022. Patients were stratified into D3 and non-D3 LND groups, with inverse-probability-weighted regression adjustment implemented to address potential confounding factors. Postoperative complications and hospital stays were analyzed using regression models and descriptive statistics.
Results D3 LND resulted in significantly higher lymph node harvests in both Stage II and Stage III patients (p < 0.01). There were no significant differences in overall or major postoperative complications between D3 and non-D3 groups. Hospital stays were comparable for Stage II patients but shorter for Stage III patients in the D3 group (p < 0.01). Complication rates ranged from 28% to 47.7%, with surgical site infections and pneumonia being the most common.
Conclusions D3 LND can be safely performed in oldest-old patients with CRC without increasing postoperative complications or extending hospital stays. These findings support the feasibility of extensive LND in this age gr en-copyright= kn-copyright= en-aut-name=InadaR. en-aut-sei=Inada en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeraishiF. en-aut-sei=Teraishi en-aut-mei=F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuhashiT. en-aut-sei=Mitsuhashi en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakanagaS. en-aut-sei=Takanaga en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToshimaT. en-aut-sei=Toshima en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhtaniT. en-aut-sei=Ohtani en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaR. en-aut-sei=Yoshida en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HoriN. en-aut-sei=Hori en-aut-mei=N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShigemitsuK. en-aut-sei=Shigemitsu en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoS. en-aut-sei=Yamamoto en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KubotaT. en-aut-sei=Kubota en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkanoY. en-aut-sei=Okano en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NobuhisaT. en-aut-sei=Nobuhisa en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaniguchiF. en-aut-sei=Taniguchi en-aut-mei=F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IshikawaW. en-aut-sei=Ishikawa en-aut-mei=W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShojiR. en-aut-sei=Shoji en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsudaT. en-aut-sei=Matsuda en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UmeokaT. en-aut-sei=Umeoka en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FujiwaraT. en-aut-sei=Fujiwara en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=Setouchi Colorectal Neoplasm Registration Study Group Collaborators en-aut-sei=Setouchi Colorectal Neoplasm Registration Study Group Collaborators en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Surgery, Kochi Health Sciences Center kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Surgery, Kagawa Rosai Hospital kn-affil= affil-num=6 en-affil=Department of Surgery, Saiseikai Okayama Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Okayama Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, Tottori Municipal Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, Tsuyama Chuo Hospital kn-affil= affil-num=10 en-affil=Department of Surgery, Okayama City Hospital kn-affil= affil-num=11 en-affil=Department of Surgery, Kobe Red Cross Hospital kn-affil= affil-num=12 en-affil=Department of Surgery, Onomichi City Hospital kn-affil= affil-num=13 en-affil=Department of Surgery, Himeji Red Cross Hospital kn-affil= affil-num=14 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=15 en-affil=Department of Surgery, Fukuyama City Hospital kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Surgery, Matsuda Hospital kn-affil= affil-num=18 en-affil=Department of Surgery, Matsuyama City Hospital kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil= kn-affil= en-keyword=Lymph node dissection kn-keyword=Lymph node dissection en-keyword=Colorectal cancer kn-keyword=Colorectal cancer en-keyword=Oldest-old patients kn-keyword=Oldest-old patients en-keyword=Postoperative complication kn-keyword=Postoperative complication END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=5 article-no= start-page=2113 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fgf10 Gene Dosage from a Single Allele Is Insufficient for Forming Multilayered Epithelial Cells in the Murine Lacrimal Gland en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mutations in the fibroblast growth factor 10 (FGF10) gene in humans cause aplasia of the lacrimal and salivary glands (ALSG). In patients with ALSG, heterozygous loss-of-function mutations are found, and FGF10 haploinsufficiency results in the absence of these secretory organs. Lacrimal glands (LGs) are formed through epithelial thickening, budding, and branching morphogenesis. To compare the variable phenotypes of the Fgf10+/− Harderian glands (HGs) previously reported, we examined the development of LGs in wild-type (WT), Fgf10+/−, and Fgf10-null mice. Pax6 immunostaining was performed to visualize the LG primordia from embryonic day 15.5 (E15.5) onwards. In situ hybridization of the genes encoding the epithelial receptor of FGF10, FGFR2b, and its other ligands was performed to determine their potential involvement in LG development. LG primordia were not observed in Fgf10+/− mice bilaterally at E16.5 or later stages. At E15.5, budding from the developing conjunctival epithelium (CE) was observed in a small fraction of the Fgf10+/− LG primordia. In contrast, the Fgf10-null CE failed to promote budding. Among Fgf1, Fgf3, Fgf7, Fgf10, and Fgf22, Fgf10 was expressed in the mesenchyme surrounding developing LG epithelial cells, whereas Fgf1 was expressed in the LG epithelium of WT mice. Fgf7 was initially expressed in the mesenchyme surrounding the nascent LG epithelium, but its expression subsequently became diffused. Thus, we conclude that among the FGFR2b ligands, initial LG formation is dependent on the mesenchymal factors FGF10 and FGF7, and FGF1 is likely to function as an epithelial factor in the LG primordia. A single allele of Fgf10 was found to be insufficient to support the budding process during LG morphogenesis. en-copyright= kn-copyright= en-aut-name=IkedaShiori en-aut-sei=Ikeda en-aut-mei=Shiori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoKeita en-aut-sei=Sato en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TajikaYuki en-aut-sei=Tajika en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujitaHirofumi en-aut-sei=Fujita en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BandoTetsuya en-aut-sei=Bando en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NohnoTsutomu en-aut-sei=Nohno en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyaishiSatoru en-aut-sei=Miyaishi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhuchiHideyo en-aut-sei=Ohuchi en-aut-mei=Hideyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiological Technology, Gumma Prefectural College of Health Sciences kn-affil= affil-num=4 en-affil=Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Legal Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=fibroblast growth factor kn-keyword=fibroblast growth factor en-keyword=Fgf10 kn-keyword=Fgf10 en-keyword=Fgf1 kn-keyword=Fgf1 en-keyword=Fgf3 kn-keyword=Fgf3 en-keyword=Fgf7 kn-keyword=Fgf7 en-keyword=Fgf22 kn-keyword=Fgf22 en-keyword=Fgfr2b kn-keyword=Fgfr2b en-keyword=mouse kn-keyword=mouse en-keyword=lacrimal gland kn-keyword=lacrimal gland en-keyword=development kn-keyword=development END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=TeMPRA: advancing continuing professional development in pediatric rheumatology in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background In the context of the global shortage of pediatric rheumatologists, mid-career specialists who can play key roles in regional education, research, and clinical practice have become increasingly important. In Japan, the Team of Mid-career Pediatric Rheumatologists Alliance (TeMPRA) was founded in 2014 to support continuing professional development (CPD) and foster collaboration among mid-career pediatric rheumatologists. The aim of this study was to characterize the current status and future perspectives of the TeMPRA members.
Methods In 2024, a cross-sectional, web-based survey was conducted among all 37 active members of the TeMPRA across Japan. Data were collected on career trajectories, educational roles, research activities, clinical practices, and international engagement. Categorical variables were compared using appropriate statistical tests, with a significance level of 0.05.
Results Responses were obtained from 35 members (response rate: 95%). Most respondents (71%) were affiliated with university hospitals, and 60% had > 10 years of experience in pediatric rheumatology. Compared with those working in community hospitals, respondents affiliated with university hospitals were significantly more likely to be involved in research activities (50% vs. 0%, P = 0.0261) and global professional contributions (88% vs. 0%, P < 0.0001). Overall, 54% of respondents were engaged in teaching students or early-career pediatric rheumatologists, while 43% were involved in clinical or basic research, most commonly focusing on juvenile idiopathic arthritis and systemic lupus erythematosus. Collectively, respondents were responsible for the care of 1,677 children with pediatric rheumatic diseases. While all respondents reported willingness to contribute to pediatric rheumatology at the regional level, 94% and 71% reported willingness to contribute at the national and global levels, respectively.
Conclusions This nationwide survey highlights the substantial educational roles, research activities, and clinical practices of mid-career pediatric rheumatologists in Japan and suggests that the TeMPRA framework can serve as a valuable model for supporting CPD and workforce sustainability. Similar alliance-based approaches may be applicable in other countries facing comparable challenges in pediatric rheumatology. en-copyright= kn-copyright= en-aut-name=WakiguchiHiroyuki en-aut-sei=Wakiguchi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HashimotoKunio en-aut-sei=Hashimoto en-aut-mei=Kunio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraKenichi en-aut-sei=Nishimura en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EbatoTakasuke en-aut-sei=Ebato en-aut-mei=Takasuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkamineKeiji en-aut-sei=Akamine en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UejimaYoji en-aut-sei=Uejima en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatoTomomi en-aut-sei=Sato en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamasakiYuichi en-aut-sei=Yamasaki en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasumuraJunko en-aut-sei=Yasumura en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkazakiFumiko en-aut-sei=Okazaki en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KizawaToshitaka en-aut-sei=Kizawa en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YasuokaRyuhei en-aut-sei=Yasuoka en-aut-mei=Ryuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IshikawaTomoaki en-aut-sei=Ishikawa en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamamotoTakeshi en-aut-sei=Yamamoto en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujitaYuji en-aut-sei=Fujita en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ItohNaohiro en-aut-sei=Itoh en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TakasakiAsami en-aut-sei=Takasaki en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SakuraiNodoka en-aut-sei=Sakurai en-aut-mei=Nodoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SuzukiKazuo en-aut-sei=Suzuki en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TamaiTasuku en-aut-sei=Tamai en-aut-mei=Tasuku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HiranoNaoki en-aut-sei=Hirano en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=OkamotoNami en-aut-sei=Okamoto en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=ShimizuMasaki en-aut-sei=Shimizu en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= affil-num=1 en-affil=Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine kn-affil= affil-num=2 en-affil=Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, Yokohama City University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kitasato University kn-affil= affil-num=6 en-affil=Department of Nephrology and Rheumatology, Tokyo Metropolitan Children’s Medical Center kn-affil= affil-num=7 en-affil=Division of Infectious Diseases and Immunology, Saitama Children’s Medical Center kn-affil= affil-num=8 en-affil=Clinical Education Center for Physicians, Shiga University of Medical Science kn-affil= affil-num=9 en-affil=Department of Pediatrics, Kagoshima University Hospital kn-affil= affil-num=10 en-affil=Department of Pediatrics, Hiroshima Prefectural Hospital Organization Futabanosato Prefectural Hospital kn-affil= affil-num=11 en-affil=Department of Pediatrics, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Pediatrics, Japan Community Health Care Organization Sapporo Hokushin Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Hamamatsu University School of Medicine kn-affil= affil-num=14 en-affil=Department of Pediatrics, Nara Medical University kn-affil= affil-num=15 en-affil=Department of Pediatrics, Chiba University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Pediatrics, Dokkyo Medical University kn-affil= affil-num=17 en-affil=Department of Pediatrics, Faculty of Medical Sciences, University of Fukui kn-affil= affil-num=18 en-affil=Department of Pediatrics, School of Medicine, University of Toyama kn-affil= affil-num=19 en-affil=Department of Pediatrics, NTT East Medical Center Sapporo kn-affil= affil-num=20 en-affil=Suzuki Kids Clinic kn-affil= affil-num=21 en-affil=Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine kn-affil= affil-num=22 en-affil=Department of Public Health and Epidemiology, Faculty of Medicine, Oita University kn-affil= affil-num=23 en-affil=Department of Pediatrics, Osaka Rosai Hospital, Japan Organization of Occupational Health and Safety kn-affil= affil-num=24 en-affil=Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= en-keyword=Child kn-keyword=Child en-keyword=Education kn-keyword=Education en-keyword=Juvenile idiopathic arthritis kn-keyword=Juvenile idiopathic arthritis en-keyword=Practice kn-keyword=Practice en-keyword=Rheumatic diseases kn-keyword=Rheumatic diseases en-keyword=Systemic lupus erythematosus kn-keyword=Systemic lupus erythematosus en-keyword=Team of mid-career pediatric rheumatologists alliance kn-keyword=Team of mid-career pediatric rheumatologists alliance END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=9 article-no= start-page=4363 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gaseous CO2 electrolysis: latest advances in electrode and electrolyzer technologies toward abating CO2 emissions en-subtitle= kn-subtitle= en-abstract= kn-abstract=The conversion of CO2 into multicarbon (C2+) products via electrochemical reduction is considered a key technology for the sustainable production of fuels and chemicals. The performance of high-rate gaseous CO2 electrolysis is governed by interrelated factors such as the electrocatalysts, electrodes, electrolytes, and cell architectures. Despite the intensive focus on catalyst research, systematic studies addressing the other components remain scarce, leaving critical gaps in our understanding toward achieving higher performance in CO2 electrolysis systems. The nanoscale design of catalyst surface electronic structures and the macroscale design of electrodes and electrolyzer architectures both influence the overall activity of the electrochemical system. In designing macroscale components, it is necessary to establish benchmarks based on a comprehensive evaluation of CO2 emissions for the entire electrolysis process, because these parameters are directly linked to output metrics such as current density and cell voltage under practical operating conditions. This review summarizes recent advances in electrodes and electrolyzers, and through life-cycle assessment (LCA), evaluates key performance indicators (KPIs) for achieving negative emissions and assesses the current technology readiness of CO2 electrolysis. en-copyright= kn-copyright= en-aut-name=KamiyaKazuhide en-aut-sei=Kamiya en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakasoneSora en-aut-sei=Nakasone en-aut-mei=Sora kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuriharaRyo en-aut-sei=Kurihara en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueAsato en-aut-sei=Inoue en-aut-mei=Asato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IrieHazuki en-aut-sei=Irie en-aut-mei=Hazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakahataShoko en-aut-sei=Nakahata en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TaniguchiSatoshi en-aut-sei=Taniguchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NguyenThuy T. H. en-aut-sei=Nguyen en-aut-mei=Thuy T. H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KataokaSho en-aut-sei=Kataoka en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=2 en-affil=Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=3 en-affil=Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=4 en-affil=Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=5 en-affil=Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=6 en-affil=Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=7 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=8 en-affil=Research Institute for Chemical Process Technology, National Institute of Advanced Industrial Science and Technology (AIST), Central 5 kn-affil= affil-num=9 en-affil=Research Institute for Chemical Process Technology, National Institute of Advanced Industrial Science and Technology (AIST), Central 5 kn-affil= affil-num=10 en-affil=Research Institute for Chemical Process Technology, National Institute of Advanced Industrial Science and Technology (AIST), Central 5 kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=6 article-no= start-page=1128 end-page=1136 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250531 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Surgery for Older Cancer Patients: Cross‐Organ Review and Good Practice Statement by the Japanese Geriatric Oncology Guideline Committee en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Although the number of older people is increasing, there is a lack of evidence and insufficient consensus regarding postoperative complications and survival in older cancer patients. In this study, we conducted a literature search and systematic review focusing on the outcomes after surgery for older cancer patients.
Methods: Literature focusing on surgical treatment for older cancer patients was extracted from Japanese clinical practice guidelines for gastric cancer, lung cancer, colorectal cancer, liver cancer, and gynecological cancers (uterine body, uterine cervix, ovary, and external genitalia and vagina). Outcomes were reviewed, and committee members determined the strength of evidence on a four-point scale (A to D), with A being the highest and D being the lowest.
Results: Older cancer patients tend to have a higher incidence of postoperative complications and postoperative syndromes, and their expected survival is generally shorter compared to non-older patients. When extensive surgeries such as para-aortic lymph node dissection and/or resection with other organs are performed for older cancer patients, the postoperative mortality rates tend to increase compared to non-older patients.
Conclusion: Surgical treatments for older cancer patients tend to result in higher morbidity even when the patients are in good health status. Nevertheless, there is still a possibility that a certain fraction of the patients achieve treatment outcomes comparable to those of non-older patients. Therefore, surgical indication and procedure for older cancer patients should be carefully determined based on surgical invasiveness and patient tolerability. en-copyright= kn-copyright= en-aut-name=TanakaChie en-aut-sei=Tanaka en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OfuchiTakashi en-aut-sei=Ofuchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueDaisuke en-aut-sei=Inoue en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugimotoKen en-aut-sei=Sugimoto en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MurofushiKeiko en-aut-sei=Murofushi en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkuyamaToru en-aut-sei=Okuyama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanukiShigeaki en-aut-sei=Watanuki en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ImamuraChiyo en-aut-sei=Imamura en-aut-mei=Chiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakaiDaisuke en-aut-sei=Sakai en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakuraiNaomi en-aut-sei=Sakurai en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WatanabeKiyotaka en-aut-sei=Watanabe en-aut-mei=Kiyotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TamuraKazuo en-aut-sei=Tamura en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SaekiToshiaki en-aut-sei=Saeki en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IshiguroHiroshi en-aut-sei=Ishiguro en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Surgery, Kyushu University Beppu Hospital kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, University of Fukui kn-affil= affil-num=5 en-affil=Department of General Geriatric Medicine, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=7 en-affil=Department of Psychiatry/Palliative Care Center, Nagoya City University West Medical Center kn-affil= affil-num=8 en-affil=National Center for Global Health and Medicine, National College of Nursing kn-affil= affil-num=9 en-affil=Advanced Cancer Translational Research Institute, Showa University kn-affil= affil-num=10 en-affil=Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Cancer Solutions Co. Ltd kn-affil= affil-num=12 en-affil=Division of Medical Oncology, Department of Medicine, School of Medicine, Teikyo University kn-affil= affil-num=13 en-affil=NPO Clinical Hematology/Oncology Treatment Study Group kn-affil= affil-num=14 en-affil=Breast Oncology Service, Saitama Medical University International Medical Center kn-affil= affil-num=15 en-affil=Breast Oncology Service, Saitama Medical University International Medical Center kn-affil= en-keyword=cancer kn-keyword=cancer en-keyword=older patients kn-keyword=older patients en-keyword=surgery kn-keyword=surgery END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=9 article-no= start-page=113274 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Extensive urine production in euryhaline red stingray for adaptation to hypoosmotic environments en-subtitle= kn-subtitle= en-abstract= kn-abstract=Maintaining water balance is a prerequisite for all organisms. Euryhaline elasmobranchs face the severest water-influx potential in fresh water (FW), as they retain high concentrations of urea even in hypotonic environments. To elucidate how they overcome this osmotic challenge, we assessed urine output in conscious euryhaline red stingrays (Hemitrygon akajei). Following acclimation to 5% diluted seawater, the stingrays increased urinary output by 87-fold—the greatest change observed in vertebrates—partly due to 6.8-fold increase in glomerular filtration rate (GFR). In the nephron, expressions of Aquaporin-1 (Aqp1), Aqp3, and Aqp15 were strongly downregulated in FW, indicating that tubular diuresis bridges the gap between GFR and final urine volume. Meanwhile, FW-acclimation upregulated Aqp1 and Aqp4 in the distinct bundle structure, which promotes urea reabsorption. Euryhaline elasmobranchs resolve the huge osmotic challenge of FW by excreting massive amounts of water and retaining osmolytes including urea through coordinated regulation of GFR and Aqp expressions. en-copyright= kn-copyright= en-aut-name=AburataniNaotaka en-aut-sei=Aburatani en-aut-mei=Naotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakagiWataru en-aut-sei=Takagi en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WongMarty Kwok-Shing en-aut-sei=Wong en-aut-mei=Marty Kwok-Shing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OgawaNobuhiro en-aut-sei=Ogawa en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurakuShigehiro en-aut-sei=Kuraku en-aut-mei=Shigehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoMana en-aut-sei=Sato en-aut-mei=Mana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaitoKazuhiro en-aut-sei=Saito en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=GodoWaichiro en-aut-sei=Godo en-aut-mei=Waichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakamotoTatsuya en-aut-sei=Sakamoto en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HyodoSusumu en-aut-sei=Hyodo en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=2 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=3 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=4 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Genomics and Evolutionary Biology, National Institute of Genetics kn-affil= affil-num=6 en-affil=Department of Genomics and Evolutionary Biology, National Institute of Genetics kn-affil= affil-num=7 en-affil=Ushimado Marine Institute, Faculty of Science, Okayama University kn-affil= affil-num=8 en-affil=Ushimado Marine Institute, Faculty of Science, Okayama University kn-affil= affil-num=9 en-affil=Ushimado Marine Institute, Faculty of Science, Okayama University kn-affil= affil-num=10 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= en-keyword=Zoology kn-keyword=Zoology en-keyword=Biochemistry kn-keyword=Biochemistry en-keyword=Animal Physiology kn-keyword=Animal Physiology END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260303 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Towards place-responsive climate change education: Mongolian primary teachers’ pedagogical judgement across urban and rural contexts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Climate change education (CCE) in primary schools is increasingly recognised as essential, yet how teachers interpret and enact CCE across diverse local contexts remains underexplored. This study examines how Mongolian primary school teachers working with students aged 6–11 in urban and rural contexts interpret and teach climate change, with particular attention to the role of place. Drawing on semi-structured interviews with 20 teachers across contrasting contexts, the study explores how environmental, cultural, and institutional conditions shape teachers’ pedagogical interpretations and classroom practices. Data were analysed using reflexive thematic analysis, informed by conceptual frameworks that position place as an active mediator of teaching and learning. Findings show that rural teachers frequently integrated traditional ecological knowledge and lived environmental experience to connect global climate processes with locally observable ecological change, emphasising livelihood impacts and intergenerational ecological memory. Urban teachers, by contrast, framed climate change through anthropogenic pressures such as air pollution, waste, and infrastructure constraints, foregrounding feasible individual actions within everyday school contexts. Across both settings, teachers exercised place-responsive pedagogical judgement by selectively adapting climate content to local realities while navigating curriculum constraints and workload pressures. The study contributes a place-responsive account of teachers’ pedagogical judgement in CCE, demonstrating how place functions not only as context but as a condition shaping pedagogical feasibility. en-copyright= kn-copyright= en-aut-name=GerelkhuuShinetsetseg en-aut-sei=Gerelkhuu en-aut-mei=Shinetsetseg kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Fiel’ardhKhalifatulloh en-aut-sei=Fiel’ardh en-aut-mei=Khalifatulloh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiiHiroki en-aut-sei=Fujii en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YembuuBatchuluun en-aut-sei=Yembuu en-aut-mei=Batchuluun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DembereldorjUuriintuya en-aut-sei=Dembereldorj en-aut-mei=Uuriintuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Humanities and Social Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=4 en-affil=Geography Department, Mongolian National University of Education kn-affil= affil-num=5 en-affil=Lifelong Learning and Distance Education Department, Mongolian National University of Education kn-affil= en-keyword=Climate change education kn-keyword=Climate change education en-keyword=place-responsive education kn-keyword=place-responsive education en-keyword=primary school teachers kn-keyword=primary school teachers en-keyword=pedagogical judgement kn-keyword=pedagogical judgement en-keyword=traditional ecological knowledge kn-keyword=traditional ecological knowledge en-keyword=urban–rural contexts kn-keyword=urban–rural contexts en-keyword=Mongolia kn-keyword=Mongolia END start-ver=1.4 cd-journal=joma no-vol=53 cd-vols= no-issue=5 article-no= start-page=e2025GL119568 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260303 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Electrical Conductivity of Amorphous and Molten CaCO3 at High Pressures and Its Implications for Mantle Conductivity Anomalies en-subtitle= kn-subtitle= en-abstract= kn-abstract=Impedance spectrometry experiments have been conducted on CaCO3 up to 15 GPa and 2,100 K to identify its state under high pressure. The melting temperature of CaCO3 was also determined by the falling of a Re sphere observed via X-ray radiography. The phase transition from aragonite to the amorphous phase does not cause a leap in the Electrical conductivity (EC), while a drastic increase in the EC, by 1.5–2.0 log units, only occurs with the onset of melting. The EC of amorphous CaCO3 is comparable to other hydrous mantle minerals at similar pressure and temperature conditions. The required fraction of amorphous CaCO3 implies that it can be excluded from the potential origins responsible for the observed high EC anomalies in the upper mantle. If the conductivity anomalies are induced by the presence of carbonate, a low-degree melting of carbonate-bearing peridotite is anticipated. en-copyright= kn-copyright= en-aut-name=ZhaoBin en-aut-sei=Zhao en-aut-mei=Bin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshinoTakashi en-aut-sei=Yoshino en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChenQi en-aut-sei=Chen en-aut-mei=Qi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YuTony en-aut-sei=Yu en-aut-mei=Tony kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhangDongzhou en-aut-sei=Zhang en-aut-mei=Dongzhou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ChenBin en-aut-sei=Chen en-aut-mei=Bin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WangYanbin en-aut-sei=Wang en-aut-mei=Yanbin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=Center for Advanced Radiation Sources, The University of Chicago kn-affil= affil-num=4 en-affil=Center for Advanced Radiation Sources, The University of Chicago kn-affil= affil-num=5 en-affil=Center for Advanced Radiation Sources, The University of Chicago kn-affil= affil-num=6 en-affil=School of Ocean and Earth Science and Technology, University of Hawaii at Manoa kn-affil= affil-num=7 en-affil=Center for Advanced Radiation Sources, The University of Chicago kn-affil= END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue= article-no= start-page=106742 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Inscribed-type spherical speed reducer with uniform reduction ratio in all directions en-subtitle= kn-subtitle= en-abstract= kn-abstract=A spherical motor is an actuator that can generate rotational motion about all three orthogonal axes. However, it is difficult to obtain high output torque from most electromagnetic spherical motors, primarily due to limitations inherent in electromagnetic actuators, such as restricted magnetic force and thermal constraints. Since its torque cannot be increased using planar gears, spherical speed reducers that transmit rotational torque along three orthogonal axes through sphere-to-sphere contact are required. One major limitation of conventional spherical speed reducers is that their size increases significantly as the reduction ratio becomes higher. To address this issue, we propose a novel inscribed-type spherical speed reducer, in which the deceleration mechanism is integrated within the output sphere. This configuration enables a more compact design, reducing the overall size to approximately half that of conventional designs. To predict the angular velocity and transmitted torque, theoretical models for the rotation and torque transmission of the speed reducer were developed. According to the proposed model, the reduction ratio of the spherical speed reducer is 1/3. To verify the validity of these models, experiments were conducted to measure angular velocity and torque. The theoretical results agreed well with the experimental results. In addition, the theoretical torque exhibited an average relative error of 1.63 % compared to the experimental result. Therefore, it was confirmed that the rotation and torque transmission models were valid. These results demonstrate that a reduction ratio can be obtained in all directions of the 3-DOF of the spherical speed reducer, unlike conventional 1-DOF reducers. en-copyright= kn-copyright= en-aut-name=NaramuraSeiya en-aut-sei=Naramura en-aut-mei=Seiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TonegawaKoichi en-aut-sei=Tonegawa en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShimookaSo en-aut-sei=Shimooka en-aut-mei=So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YanoTomoaki en-aut-sei=Yano en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GofukuAkio en-aut-sei=Gofuku en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KasashimaNagayoshi en-aut-sei=Kasashima en-aut-mei=Nagayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamegawaTetsushi en-aut-sei=Kamegawa en-aut-mei=Tetsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Okayama Prefectural University kn-affil= affil-num=6 en-affil=National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=7 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Inscribed-type spherical speed reducer kn-keyword=Inscribed-type spherical speed reducer en-keyword=Rotation and torque transmission kn-keyword=Rotation and torque transmission en-keyword=Friction kn-keyword=Friction en-keyword=Spherical motor kn-keyword=Spherical motor en-keyword=Three-axis rotation kn-keyword=Three-axis rotation END start-ver=1.4 cd-journal=joma no-vol=2026 cd-vols= no-issue=2 article-no= start-page=023F01 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Feedback-Controlled Beam Pattern Measurement Method Using a Power-Variable Calibration Source for Cosmic Microwave Background Telescopes en-subtitle= kn-subtitle= en-abstract= kn-abstract=We demonstrate a novel beam pattern measurement method for the side lobe characterization of cosmic microwave background telescopes. The method employs a power-variable artificial microwave source under feedback control from the detector under test on the telescope. It enables us to extend the dynamic range of the beam pattern measurement without introducing nonlinearity effects from the detector. We conducted a laboratory-based proof-of-concept experiment, measuring the H-plane beam pattern of a horn antenna coupled to a diode detector at 81 GHz. We gained an additional dynamic range of 60.3 dB attributed to the feedback control. In addition, we verified the measurement by comparing it with other reference measurements obtained using conventional methods. The method is also applicable to general optical measurements requiring a high dynamic range to detect subtle nonidealities in the characteristics of optical devices. en-copyright= kn-copyright= en-aut-name=HiroseHaruaki en-aut-sei=Hirose en-aut-mei=Haruaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HasegawaMasaya en-aut-sei=Hasegawa en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanekoDaisuke en-aut-sei=Kaneko en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagasakiTaketo en-aut-sei=Nagasaki en-aut-mei=Taketo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakakuRyota en-aut-sei=Takaku en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=de HaanTijmen en-aut-sei=de Haan en-aut-mei=Tijmen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakakuraSatoru en-aut-sei=Takakura en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujinoTakuro en-aut-sei=Fujino en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Physics, Graduate School of Engineering Science, Yokohama National University kn-affil= affil-num=2 en-affil=Institute of Particle and Nuclear Studies (IPNS), High Energy Accelerator Research Organization (KEK) kn-affil= affil-num=3 en-affil=International Center for Quantum-field Measurement Systems for Studies of the Universe and Particles (WPI-QUP), High Energy Accelerator Research Organization (KEK) kn-affil= affil-num=4 en-affil=Accelerator Laboratory (ACCL), High Energy Accelerator Research Organization (KEK) kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Institute of Particle and Nuclear Studies (IPNS), High Energy Accelerator Research Organization (KEK) kn-affil= affil-num=7 en-affil=Department of Physics, Faculty of Science, The University of Tokyo kn-affil= affil-num=8 en-affil=International Center for Quantum-field Measurement Systems for Studies of the Universe and Particles (WPI-QUP), High Energy Accelerator Research Organization (KEK) kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=2 article-no= start-page=275 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Study on the Development of an Image Classification System for Urban Sprawl Areas in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=In Japan, unlike in many other countries, urbanization has progressed while original rural road structures have been retained, leading to distinctive urban sprawl areas with intermingling residential lots and farmland. Currently, much of Japan’s urban areas consist of urban sprawl areas, posing considerable challenges for infrastructure development. However, for such urban sprawl areas in Japan, it is difficult to say that methods have been established to identify their spatial distribution based on quantitative evaluation. Therefore, for this study, we used machine learning to investigate a system that extracts sprawling urban areas from aerial photographs divided into meshes. In the system’s design, we prioritized precision to ensure the reliable detection of urban sprawl areas. Consequently, the accuracy of identifying sprawl areas achieved precision of 0.81, recall of 0.63, and an F-score of 0.71. Examination of the classification results of sprawl areas revealed that most misclassifications occurred near class boundaries. By contrast, areas with particularly high levels of urban sprawl showed few misclassifications. en-copyright= kn-copyright= en-aut-name=HemmiRyota en-aut-sei=Hemmi en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UjiharaTakehito en-aut-sei=Ujihara en-aut-mei=Takehito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AndoRyosuke en-aut-sei=Ando en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HashimotoSeiji en-aut-sei=Hashimoto en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=National Institute for Land and Infrastructure Management, Ministry of Land, Infrastructure Transport and Tourism kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=image classification kn-keyword=image classification en-keyword=machine learning kn-keyword=machine learning en-keyword=sprawl kn-keyword=sprawl END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=e100872 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Saliva as a Reliable and Non-invasive Sample for Detecting Influenza A in Severe Acute Respiratory Infection Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Nasopharyngeal swab sampling remains the gold standard for influenza diagnosis; however, it has several limitations, including dependence on medical staff, invasiveness, potential for nosocomial transmission, and occupational exposure risk. Non-invasive alternatives, such as saliva and nasal vestibular swabs, may improve patient comfort and participation in clinical studies. In addition, diagnosis with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) is often delayed because it requires trained laboratory technicians and facilities with appropriate laboratory settings. Although rapid diagnostic devices such as the GenPad® offer potential alternatives to RT-qPCR, their performance with non-invasive samples remains insufficiently explored. This study addresses the two key questions for influenza detection in severe acute respiratory infection (SARI) cases: (i) whether saliva or nasal vestibular swab samples serve as suitable alternatives to nasopharyngeal swab samples, and (ii) whether the GenPad® provides a reliable option for detecting influenza using saliva samples.
Methodology
A prospective observational study was conducted with 16 inpatients classified as having SARIs and diagnosed with influenza between December 2024 and March 2025 in Japan. Paired saliva and nasal vestibular swab samples were collected 1-9 (median = 3.5) days after symptom onset. RT-qPCR testing was performed according to the National Institute of Infectious Diseases protocol. Saliva samples were also tested using the GenPad® system. Comparisons between sample types and diagnostic methods were analyzed using the exact McNemar's test.
Results
Among the 16 influenza-positive patients, saliva samples demonstrated higher sensitivity (87.5%) than nasal vestibular swabs (31.3%) in RT-qPCR when compared with the diagnostic results obtained from nasopharyngeal swabs. A comparison of RT-qPCR results between saliva and nasal vestibular swabs revealed a total agreement of 43.8%, with exact McNemar's test showing a significant difference (p = 0.0039). While nasal vestibular swabs showed inconsistent results, saliva samples consistently tested positive, particularly within seven days of symptom onset (100% positive agreement). The GenPad®, a rapid diagnostic device, showed promising performance (92.9%) using saliva samples compared to RT-qPCR.
Conclusions
Saliva is a reliable non-invasive alternative to nasopharyngeal swabs for influenza detection in SARI cases, particularly within seven days of symptom onset, whereas nasal vestibular swabs show lower sensitivity. Additionally, the GenPad® provides comparable performance to RT-qPCR using saliva samples, offering a rapid, portable diagnostic option. These approaches may mitigate discomfort, minimize infection risk for healthcare workers, and improve testing capacity. However, the absence of influenza-negative controls and the small sample size (n = 16) substantially limit the assessment of diagnostic accuracy and specificity. As a result, the broader applicability of our findings should be interpreted with caution, and further studies are required to validate these observations. en-copyright= kn-copyright= en-aut-name=TakeuchiJunko S en-aut-sei=Takeuchi en-aut-mei=Junko S kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsunagaNobuaki en-aut-sei=Matsunaga en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsukadaAi en-aut-sei=Tsukada en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwamotoNoriko en-aut-sei=Iwamoto en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FuwaNoriko en-aut-sei=Fuwa en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IchikawaTakahiro en-aut-sei=Ichikawa en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatoYasuyuki en-aut-sei=Kato en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TomitaYuka en-aut-sei=Tomita en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KitagawaHiroki en-aut-sei=Kitagawa en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamatoMasaya en-aut-sei=Yamato en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AoyagiTetsuji en-aut-sei=Aoyagi en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HaseRyota en-aut-sei=Hase en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HatakeyamaShuji en-aut-sei=Hatakeyama en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=InabaTohru en-aut-sei=Inaba en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IzumikawaKoichi en-aut-sei=Izumikawa en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakesueYoshio en-aut-sei=Takesue en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KimuraMoto en-aut-sei=Kimura en-aut-mei=Moto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OhmagariNorio en-aut-sei=Ohmagari en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=2 en-affil=Antimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health Security kn-affil= affil-num=3 en-affil=Antimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health Security kn-affil= affil-num=4 en-affil=Disease Control and Prevention Center, Japan Institute for Health Security kn-affil= affil-num=5 en-affil=Disease Control and Prevention Center, Japan Institute for Health Security kn-affil= affil-num=6 en-affil=Department of Infectious Diseases, Sapporo City General Hospital kn-affil= affil-num=7 en-affil=Department of Infectious Diseases, International University of Health and Welfare (IUHW) Narita Hospital kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital kn-affil= affil-num=9 en-affil=Department of Infectious Diseases, Hiroshima University Hospital kn-affil= affil-num=10 en-affil=Department of General Internal Medicine and Infectious Diseases, Rinku General Medical Center kn-affil= affil-num=11 en-affil=Department of Clinical Infectious Diseases, Tohoku University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Infectious Diseases, Japanese Red Cross Narita Hospital kn-affil= affil-num=14 en-affil=Division of Infectious Diseases, Jichi Medical University Hospital kn-affil= affil-num=15 en-affil=Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine kn-affil= affil-num=16 en-affil= kn-affil= affil-num=17 en-affil=Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=18 en-affil=Department of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=19 en-affil=Disease Control and Prevention Center, Japan Institute for Health Security kn-affil= en-keyword=influenza a kn-keyword=influenza a en-keyword=nasal vestibular swab kn-keyword=nasal vestibular swab en-keyword=nasopharyngeal swab kn-keyword=nasopharyngeal swab en-keyword=rapid diagnostics kn-keyword=rapid diagnostics en-keyword=rt-qpcr kn-keyword=rt-qpcr en-keyword=saliva kn-keyword=saliva en-keyword=sari kn-keyword=sari END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1 article-no= start-page=55 end-page=62 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Changes in Prescribing Patterns of Antiviral Drugs before and after Public Coverage Termination among Hospitalized COVID-19 Patients in Regional Hospitals in Japan: A Retrospective, Multicenter Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=In Japan, antiviral agents for COVID-19 were freely available until September 2023 as part of national policy. This study evaluated changes in these agents’ prescribing patterns and the patient outcomes following the policy shift. We conducted a multicenter retrospective study at four hospitals in Japan’s Okayama and Kagawa prefectures from January 2022 to March 2024. The study period was divided into the public-expenditure phase (January 2022 to September 2023) and the post-expenditure phase (October 2023 to March 2024). We extracted the hospitalized patients’ clinical data from the electronic database. The study’s primary outcome was the antiviral prescription rate; the secondary outcome was in-hospital mortality. Among the 302 hospitalized patients (median age 85 years), 52.0% were classified as having a mild condition. Of the patients with mild conditions, 37.7% were diagnosed in outpatient settings prior to hospitalization. During the public-expenditure phase, 47.4% of the patients received antivirals as outpatients, mainly molnupiravir (80.9%). In the post-expenditure period, 80.0% of the patients were prescribed antivirals, mostly molnupiravir (91.7%). The antiviral prescription rate was significantly higher after the policy change. The overall in-hospital mortality was 15.8%, with no significant difference between the two periods (17.0% vs. 10.5%). Despite the termination of government funding, antiviral prescriptions remained frequent at community hospitals located in highly aging regions of western Japan such as Okayama and Kagawa prefectures. Mortality remains high among the elderly, highlighting the need for continued antiviral therapy and booster vaccinations. en-copyright= kn-copyright= en-aut-name=AkazawaHidemasa en-aut-sei=Akazawa en-aut-mei=Hidemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoShohei en-aut-sei=Yamamoto en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanoYasuhiro en-aut-sei=Nakano en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, kn-affil= en-keyword=coronavirus disease 2019 kn-keyword=coronavirus disease 2019 en-keyword=public expenditure kn-keyword=public expenditure en-keyword=prescribing pattern kn-keyword=prescribing pattern en-keyword=prognosis kn-keyword=prognosis en-keyword=Japan kn-keyword=Japan END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1 article-no= start-page=17 end-page=30 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of a Stroke Discharge Support Evaluation Scale for Ward Nurses in Acute Care Hospitals en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study aimed to develop a scale enabling nurses to objectively evaluate their own stroke discharge support, as a basis for enhancing its overall effectiveness. A draft scale was created based on a literature review, and consisted of a 51-item, 5-point Likert-type questionnaire administered to ward nurses engaged in stroke discharge support at acute care hospitals. Factor analysis was performed to refine the scale. Construct validity was assessed using the known-groups method, and reliability was evaluated through internal consistency analysis. The resulting Stroke Discharge Support Evaluation Scale comprises 29 items across 5 factors, each rated on a 5-point Likert scale. Analysis of the data collected from 237 valid responses demonstrated good internal consistency and supported the scale’s construct validity. The Stroke Discharge Support Evaluation Scale is a reliable and valid tool enabling ward nurses in acute care hospitals to evaluate their own stroke discharge support. en-copyright= kn-copyright= en-aut-name=YanoHideki en-aut-sei=Yano en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahataYoko en-aut-sei=Takahata en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamaguchiTakeshi en-aut-sei=Yamaguchi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitoShinya en-aut-sei=Saito en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Nursing, Faculty of Human Health Sciences, Niimi University kn-affil= affil-num=2 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Nursing, Shikoku University kn-affil= affil-num=4 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=stroke kn-keyword=stroke en-keyword=discharge support kn-keyword=discharge support en-keyword=scale development kn-keyword=scale development END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue= article-no= start-page=20 end-page=39 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Radiocarbon dating, dietary habits, and genetic characteristics of ancient skeletal remains excavated from the Inome Cave Site in Shimane Prefecture kn-title=島根県猪目洞窟遺跡出土人骨の年代・食性・遺伝的特徴 en-subtitle= kn-subtitle= en-abstract= kn-abstract=This paper reports on the integrative research findings of the human bones excavated from the Inome Cave Site in Shimane Prefecture, based on dietary estimation using carbon and nitrogen isotope analysis, radiocarbon dating, and whole genome analysis. The dates of the analyzed human bones span a wide range, from the Middle to Late Kofun period, the Nara period to the Early Heian period, and the Middle to Late Heian period, indicating that the Inome Cave Site was continuously used as a burial place. Dietary habits were a mixture of C3 resources (C3 plants and terrestrial animals that consumed C3 plants) and marine resources, with individual variations in the intake of marine and terrestrial resources. A correlation was observed between differences in dietary habits and individual variations in the Jomon ratio in the nuclear genome, with individuals who consumed higher amounts of marine resources tending to have a higher Jomon ratio. This suggests that individuals with different backgrounds were buried in the same site due to interactions with surrounding settlements. en-copyright= kn-copyright= en-aut-name=KANZAWA-KIRIYAMAHideaki en-aut-sei=KANZAWA-KIRIYAMA en-aut-mei=Hideaki kn-aut-name=神澤秀明 kn-aut-sei=神澤 kn-aut-mei=秀明 aut-affil-num=1 ORCID= en-aut-name=TAKIGAMIMai en-aut-sei=TAKIGAMI en-aut-mei=Mai kn-aut-name=瀧上舞 kn-aut-sei=瀧上 kn-aut-mei=舞 aut-affil-num=2 ORCID= en-aut-name=KAKUDATsuneo en-aut-sei=KAKUDA en-aut-mei=Tsuneo kn-aut-name=角田恒雄 kn-aut-sei=角田 kn-aut-mei=恒雄 aut-affil-num=3 ORCID= en-aut-name=SPEIDELLeo en-aut-sei=SPEIDEL en-aut-mei=Leo kn-aut-name=シュパイデルレオ kn-aut-sei=シュパイデル kn-aut-mei=レオ aut-affil-num=4 ORCID= en-aut-name=HELLENTHALGarrett en-aut-sei=HELLENTHAL en-aut-mei=Garrett kn-aut-name=ヘレンタールガレット kn-aut-sei=ヘレンタール kn-aut-mei=ガレット aut-affil-num=5 ORCID= en-aut-name=BIRDNancy en-aut-sei=BIRD en-aut-mei=Nancy kn-aut-name=バードナンシー kn-aut-sei=バード kn-aut-mei=ナンシー aut-affil-num=6 ORCID= en-aut-name=KAWAIYousuke en-aut-sei=KAWAI en-aut-mei=Yousuke kn-aut-name=河合洋介 kn-aut-sei=河合 kn-aut-mei=洋介 aut-affil-num=7 ORCID= en-aut-name=NCBN Controls WGS Consortium en-aut-sei=NCBN Controls WGS Consortium en-aut-mei= kn-aut-name=NCBN コントロール WGS コンソーシアム kn-aut-sei=NCBN コントロール WGS コンソーシアム kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SAKAMOTOMinoru en-aut-sei=SAKAMOTO en-aut-mei=Minoru kn-aut-name=坂本稔 kn-aut-sei=坂本 kn-aut-mei=稔 aut-affil-num=9 ORCID= en-aut-name=KAMEDAYuichi en-aut-sei=KAMEDA en-aut-mei=Yuichi kn-aut-name=亀田勇一 kn-aut-sei=亀田 kn-aut-mei=勇一 aut-affil-num=10 ORCID= en-aut-name=ADACHINoboru en-aut-sei=ADACHI en-aut-mei=Noboru kn-aut-name=安達登 kn-aut-sei=安達 kn-aut-mei=登 aut-affil-num=11 ORCID= en-aut-name=SHINODAKen-ichi en-aut-sei=SHINODA en-aut-mei=Ken-ichi kn-aut-name=篠田謙一 kn-aut-sei=篠田 kn-aut-mei=謙一 aut-affil-num=12 ORCID= en-aut-name=SAITOUNaruya en-aut-sei=SAITOU en-aut-mei=Naruya kn-aut-name=斎藤成也 kn-aut-sei=斎藤 kn-aut-mei=成也 aut-affil-num=13 ORCID= en-aut-name=HAMADATatsuhiko en-aut-sei=HAMADA en-aut-mei=Tatsuhiko kn-aut-name=濵田竜彦 kn-aut-sei=濵田 kn-aut-mei=竜彦 aut-affil-num=14 ORCID= affil-num=1 en-affil=Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture kn-affil= affil-num=2 en-affil=Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture kn-affil= affil-num=3 en-affil=Department of Legal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi kn-affil= affil-num=4 en-affil=Center for Interdisciplinary Theoretical and Mathematical Sciences, RIKEN kn-affil= affil-num=5 en-affil=Department of Genetics, Evolution and Environment, University College London Genetics Institute (UGI), University College London kn-affil= affil-num=6 en-affil=Department of Genetics, Evolution and Environment, University College London Genetics Institute (UGI), University College London kn-affil= affil-num=7 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine, National Institute for Health Security kn-affil= affil-num=8 en-affil= kn-affil= affil-num=9 en-affil=National Museum of Japanese History kn-affil= affil-num=10 en-affil=Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture kn-affil= affil-num=11 en-affil=Department of Legal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi kn-affil= affil-num=12 en-affil=National Museum of Nature and Science kn-affil= affil-num=13 en-affil=National Institute of Genetics kn-affil= affil-num=14 en-affil=Research Institute for the Dynamics of Civilizations, Okayama University kn-affil= en-keyword=Inome Cave Site kn-keyword=Inome Cave Site en-keyword=human bone kn-keyword=human bone en-keyword=radiocarbon dating kn-keyword=radiocarbon dating en-keyword=dietary habits kn-keyword=dietary habits en-keyword=ancient genome kn-keyword=ancient genome END start-ver=1.4 cd-journal=joma no-vol=153 cd-vols= no-issue=3 article-no= start-page=191 end-page=199 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Schizophrenia Spectrum Disorders on the Receipt of Invasive and Systemic Therapy for Colorectal Cancer: A Nationwide Multicenter Retrospective Cohort Study in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: This study examined treatment disparities for colorectal cancer among patients diagnosed with schizophrenia spectrum disorders (SSD), focusing on invasive treatments and stage-appropriate systemic therapy within a universal healthcare system.
Method: In this nationwide retrospective cohort study (2018–2021), we identified 248,966 colorectal cancer patients, including 2337 diagnosed with SSD, using linked cancer registry and insurance claims data in Japan. The presence of SSD was classified according to ICD-10 codes F20–29. We used multivariable logistic regression to compare the odds of receiving stage-appropriate adjuvant chemotherapy and systemic therapy, as well as the odds of receiving surgical or endoscopic treatments, between the two groups. The analysis adjusted for age, sex, clinical stage, and scores on the Charlson Comorbidity Index and Barthel Index.
Results: The clinical stage distribution at diagnosis for colorectal cancer differed significantly between patients with SSD and those without psychiatric disorders (p < 0.001). After adjusting for clinical stage and other covariates, patients with SSD demonstrated significantly lower odds of receiving surgical or endoscopic treatment (adjusted odds ratio [aOR], 0.83; 95% CI, 0.73–0.94). The disparities were more pronounced for systemic therapy; patients with SSD had substantially lower odds of receiving adjuvant chemotherapy for stage III disease (aOR, 0.33; 95% CI, 0.26–0.41) and systemic therapy for stage IV disease (aOR, 0.23; 95% CI, 0.17–0.31).
Conclusion: Patients with SSD encounter substantial disparities in accessing standard colorectal cancer care, particularly systemic therapies. These findings highlight the urgent need for interventions to ensure equitable cancer treatment for this vulnerable population. en-copyright= kn-copyright= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaYuto en-aut-sei=Yamada en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshiiTaisuke en-aut-sei=Ishii en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeTomone en-aut-sei=Watanabe en-aut-mei=Tomone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujimoriMaiko en-aut-sei=Fujimori en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakayaNaoki en-aut-sei=Nakaya en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawamuraToshihiko en-aut-sei=Kawamura en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OtsukiKoji en-aut-sei=Otsuki en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShimazuTaichi en-aut-sei=Shimazu en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HinotsuShiro en-aut-sei=Hinotsu en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UchitomiYosuke en-aut-sei=Uchitomi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=InagakiMasatoshi en-aut-sei=Inagaki en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Medical Development Field, Okayama University kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=4 en-affil=Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=5 en-affil=Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=6 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=7 en-affil=Department of Medical Informatics, Shimane University Hospital kn-affil= affil-num=8 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Medical Development Field, Okayama University kn-affil= affil-num=10 en-affil=Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=11 en-affil=Department of Biostatistics and Data Management, Sapporo Medical University kn-affil= affil-num=12 en-affil=Department of Cancer Survivorship and Digital Medicine, The Jikei University School of Medicine kn-affil= affil-num=13 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=healthcare disparities kn-keyword=healthcare disparities en-keyword=psycho-oncology kn-keyword=psycho-oncology en-keyword=schizophrenia spectrum disorders kn-keyword=schizophrenia spectrum disorders END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=4 article-no= start-page=201045 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Collagen depletion by pirfenidone enhances antitumor effect of oncolytic adenovirus against peritoneal metastases of gastric cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer-associated fibroblasts (CAFs) play a crucial role in collagen accumulation, which develops and promotes peritoneal metastasis (PM) in gastric cancer (GC). In addition, the abundant stromal collagens in the tumor microenvironment function as a physical barrier against penetration of antitumor drugs and oncolytic viruses. This study investigated whether collagen depletion by pirfenidone (PFD), an antifibrotic drug, enhances the antitumor effects of oncolytic adenoviruses. Analysis of the clinical samples revealed a significant association of high expression of collagen 1 and α-smooth muscle actin (α-SMA) with PM development and poor prognosis of advanced GC. Human and murine GC cells enhanced collagen production by fibroblasts, which was suppressed by PFD. Abundant fibroblasts and collagen inhibited the penetration of OBP-702, which reduced the antitumor effects of OBP-702 in the spheroid model. Intraperitoneal co-injection of GC cells and fibroblasts promoted the development of collagen-rich PM and reduced the antitumor effects of OBP-702 in vivo model. PFD suppressed collagen production in PM and improved viral penetration into the tumors, which enhanced the antitumor effects of OBP-702 against PM of GC. Collagen depletion by PFD enhances the penetration of OBP-702 into PM of GC, in turn enhancing the antitumor effects of OBP-702 against PM of GC. en-copyright= kn-copyright= en-aut-name=OkuraTomohiro en-aut-sei=Okura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MikaneYu en-aut-sei=Mikane en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsuiEma en-aut-sei=Mitsui en-aut-mei=Ema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UneYuta en-aut-sei=Une en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhtsukaJunko en-aut-sei=Ohtsuka en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OhkiRieko en-aut-sei=Ohki en-aut-mei=Rieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute kn-affil= affil-num=13 en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil= Oncolys BioPharma, Inc. kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=MT: Regular Issue kn-keyword=MT: Regular Issue en-keyword=oncolytic virotherapy kn-keyword=oncolytic virotherapy en-keyword=peritoneal metastasis kn-keyword=peritoneal metastasis en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=collagen kn-keyword=collagen en-keyword=pirfenidone kn-keyword=pirfenidone END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=9 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sodium butyrate augments the antibacterial activity of tetracycline against clinical isolates of multidrug-resistant Vibrio cholerae en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Antibiotic resistance poses a major challenge in treating Vibrio cholerae infections. One promising method to counter resistance is the co-administration of antibiotics with non-antibiotic adjuvants to enhance their efficacy. This study investigated the combined action of sodium butyrate (SB) and tetracycline on tetracycline-resistant V. cholerae strains.
Results The combined activity of SB and antibiotics was assessed on eight V. cholerae clinical isolates using the Fractional Inhibitory Concentration Index (FICI), with SB-Tetracycline showing strong synergy (FICI: 0.09–0.5). Functional and mechanistic studies, including time-kill kinetics, live/dead staining, SEM-based morphological analysis, and fluorometric assays, demonstrated a synergistic antibacterial effect of SB and Tetracycline. This effect was associated with increased membrane permeability, disruption of membrane integrity, dissipation of the proton motive force, and suppression of efflux activity. These changes collectively led to membrane damage, enhanced intracellular accumulation of Tetracycline, decreased intracellular ATP levels, and ultimately, bacterial cell death. Moreover, GM1-CT ELISA and fluorescence microscopy revealed the synergistic anti-virulence activity of the SB- Tetracycline combination. Finally, the combination of SB and Tetracycline showed enhanced efficacy in animal models compared with monotherapy.
Conclusion: The observed SB-Tetracycline synergy provides a promising therapeutic approach to overcome tetracycline resistance in V. cholerae, offering a potential adjunct strategy for the management of antibiotic-resistant cholera infections. en-copyright= kn-copyright= en-aut-name=KunduSushmita en-aut-sei=Kundu en-aut-mei=Sushmita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AluSourin en-aut-sei=Alu en-aut-mei=Sourin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SinghAbhishek en-aut-sei=Singh en-aut-mei=Abhishek kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GopeAnimesh en-aut-sei=Gope en-aut-mei=Animesh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NandyRanjan Kumar en-aut-sei=Nandy en-aut-mei=Ranjan Kumar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MukhopadhyayAsish K. en-aut-sei=Mukhopadhyay en-aut-mei=Asish K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ChatterjeeNabendu Sekhar en-aut-sei=Chatterjee en-aut-mei=Nabendu Sekhar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BhattacharyaSushmita en-aut-sei=Bhattacharya en-aut-mei=Sushmita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections kn-affil= affil-num=2 en-affil=Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections kn-affil= affil-num=3 en-affil=Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections kn-affil= affil-num=4 en-affil=Division of General Medicine, ICMR- National Institute for Research in Bacterial Infections kn-affil= affil-num=5 en-affil=Division of Bacteriology, ICMR- National Institute for Research in Bacterial Infections kn-affil= affil-num=6 en-affil=Division of Bacteriology, ICMR- National Institute for Research in Bacterial Infections kn-affil= affil-num=7 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections kn-affil= affil-num=9 en-affil=Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections kn-affil= en-keyword=V. cholerae kn-keyword=V. cholerae en-keyword=Sodium butyrate kn-keyword=Sodium butyrate en-keyword=Tetracycline kn-keyword=Tetracycline en-keyword=Synergy kn-keyword=Synergy en-keyword=Antibiotic adjuvant kn-keyword=Antibiotic adjuvant END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=3 article-no= start-page=563 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260131 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of Surface Morphology Formed by Additive Manufacturing on the Adhesion of Dental Cements to Zirconia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Durable bonding to zirconia remains difficult because its chemically inert surface resists acid etching. Additive manufacturing (AM) enables controlled surface morphology, which may enhance micromechanical retention without additional treatments. Methods: Zirconia specimens with three AM-derived surface designs—(1) concave–convex hemispherical patterns, (2) concave hemispherical patterns, and (3) as-printed surfaces—were fabricated using a slurry-based 3D printing system and sintered at 1500 °C. Zirconia specimens fabricated by subtractive manufacturing using CAD/CAM systems, polished with 15 µm diamond lapping film and with or without subsequent alumina sandblasting, served as controls. Surface morphology was analyzed by FE-SEM, and shear bond strength (SBS) was tested after cementation with a resin-based luting agent. Results: SEM revealed regular layered textures and designed hemispherical structures (~300 µm) in AM specimens, along with step-like irregularities (~40 µm) at layer boundaries. The concave–convex AM group showed significantly higher SBS than both sandblasted and polished subtractive-manufactured zirconia (p < 0.05). Vertically printed specimens demonstrated greater bonding strength than those printed parallel to the bonding surface, indicating that build orientation affects resin infiltration and interlocking. Conclusion: AM-derived zirconia surfaces can provide superior and reproducible micromechanical retention compared with conventional treatments. Further optimization of printing parameters and evaluation of long-term durability are needed for clinical application. en-copyright= kn-copyright= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LeeSungho en-aut-sei=Lee en-aut-mei=Sungho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaruoYukinori en-aut-sei=Maruo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SpirrettFiona en-aut-sei=Spirrett en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KiriharaSoshu en-aut-sei=Kirihara en-aut-mei=Soshu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaYasuhiro en-aut-sei=Yoshida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Van MeerbeekBart en-aut-sei=Van Meerbeek en-aut-mei=Bart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=National Institute of Advanced Industrial Science and Technology (AIST), Health and Medical Research Institute kn-affil= affil-num=2 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School kn-affil= affil-num=3 en-affil=National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=4 en-affil=Department of Prosthodontics, Okayama University kn-affil= affil-num=5 en-affil=Joining and Welding Research Institute, Osaka University kn-affil= affil-num=6 en-affil=Joining and Welding Research Institute, Osaka University kn-affil= affil-num=7 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=8 en-affil=Department of Oral Health Sciences, BIOMAT, KU Leuven kn-affil= en-keyword=additive manufacturing kn-keyword=additive manufacturing en-keyword=bond strength kn-keyword=bond strength en-keyword=dental crown kn-keyword=dental crown en-keyword=dental resin cement kn-keyword=dental resin cement en-keyword=dental zirconia kn-keyword=dental zirconia END start-ver=1.4 cd-journal=joma no-vol=123 cd-vols= no-issue=6 article-no= start-page=e2518136123 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A nuclear CobW/WW-domain factor represses the CO2-concentrating mechanism in the green alga Chlamydomonas reinhardtii en-subtitle= kn-subtitle= en-abstract= kn-abstract=Microalgae induce a CO2-concentrating mechanism (CCM) to maintain photosynthesis when CO2 is limited. Because this system consumes a substantial portion of photosynthetically generated ATP, its suppression when CO2 levels rise is critical for energy balance, yet the underlying mechanism remains unclear. Here, we identify a nuclear repressor of the CCM in the green alga Chlamydomonas reinhardtii. A pull-down screen for interacting partners of the master activator CCM1/CIA5 revealed an uncharacterized protein that tightly associates with CCM1. This protein, CCM1-binding protein 1 (CBP1), combines a CobW/CobW_C GTP-binding metallochaperone module with a WW-domain characteristic of protein–protein interactions. CBP1 colocalizes and interacts with CCM1 in the nucleus regardless of CO2 conditions. Disruption of CBP1 does not affect growth or CCM induction under CO2 limitation but derepresses 27 of 41 CCM1-dependent low-CO2 inducible genes under high-CO2 conditions. These include the periplasmic and intracellular carbonic anhydrases (CAH1 and LCIB) and inorganic carbon transporters/channels (LCIA, LCI1, BST1, and BST3). Consistently, cbp1 mutants accumulate CAH1 and LCIB proteins and exhibit 40% higher inorganic carbon affinity under high-CO2 conditions; this phenotype is rescued by CBP1 complementation or by acetazolamide treatment. Crucially, cbp1 mutants exhibit significant growth delays under high-CO2 conditions, especially when light is limiting, providing direct evidence that CBP1-mediated repression is essential for energy conservation. Thus, CBP1 prevents unnecessary CCM activity when CO2 is abundant, acting upstream of both transporter/channel and carbonic anhydrase modules. Our findings suggest a regulatory mechanism potentially linking zinc-dependent protein chemistry to CCM gene repression, providing insights into energy-efficient CO2 sensing in aquatic photosynthetic organisms. en-copyright= kn-copyright= en-aut-name=ShimamuraDaisuke en-aut-sei=Shimamura en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YasudaJunko en-aut-sei=Yasuda en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamaharaYosuke en-aut-sei=Yamahara en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakanoHirobumi en-aut-sei=Nakano en-aut-mei=Hirobumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OzawaShin-Ichiro en-aut-sei=Ozawa en-aut-mei=Shin-Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TokutsuRyutaro en-aut-sei=Tokutsu en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamagamiAyumi en-aut-sei=Yamagami en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsushitaTomonao en-aut-sei=Matsushita en-aut-mei=Tomonao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakahashiYuichiro en-aut-sei=Takahashi en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakanoTakeshi en-aut-sei=Nakano en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FukuzawaHideya en-aut-sei=Fukuzawa en-aut-mei=Hideya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamanoTakashi en-aut-sei=Yamano en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=2 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=3 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=4 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Science, Division of Biological Sciences, Kyoto University kn-affil= affil-num=7 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=8 en-affil=Graduate School of Science, Division of Biological Sciences, Kyoto University kn-affil= affil-num=9 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=11 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=12 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= en-keyword=carbonic anhydrase kn-keyword=carbonic anhydrase en-keyword=Chlamydomonas reinhardtii kn-keyword=Chlamydomonas reinhardtii en-keyword=CO2-concentrating mechanism kn-keyword=CO2-concentrating mechanism en-keyword=photosynthesis kn-keyword=photosynthesis en-keyword=pyrenoid kn-keyword=pyrenoid END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=1 article-no= start-page=116781 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immunopeptidomics combined with full-length transcriptomics uncovers diverse neoantigens en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neoantigens are crucial for antitumor immunity and immune checkpoint inhibitor (ICI) efficacy by triggering strong immune responses. However, conventional methods for identifying neoantigens, such as whole-exon sequencing and short-read RNA sequencing (RNA-seq), appear to be insufficient, and the tumor mutational burden cannot sufficiently predict ICI efficacy. In this study, we employed a proteogenomic approach using long-read RNA-seq with Pacific Biosciences Single-Molecule Real-Time Sequencing technology to analyze full-length transcripts in combination with the human leukocyte antigen ligandome. As a result, many neoantigen candidates were identified, which were unregistered in a comprehensive database, including those from non-coding regions. Additionally, we validated the responses of specific T cell receptors (TCRs) to these candidates and identified several pairs of TCRs and neoantigens. These findings highlight the presence of more diverse neoantigens than expected that cannot be identified by conventional methods. en-copyright= kn-copyright= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeTomofumi en-aut-sei=Watanabe en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokitaSerina en-aut-sei=Tokita en-aut-mei=Serina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawaseKatsushige en-aut-sei=Kawase en-aut-mei=Katsushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakanoYuka en-aut-sei=Takano en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ThuYin Min en-aut-sei=Thu en-aut-mei=Yin Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SuzukiYuta en-aut-sei=Suzuki en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OwaChie en-aut-sei=Owa en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ZhouWenhao en-aut-sei=Zhou en-aut-mei=Wenhao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KochinVitaly en-aut-sei=Kochin en-aut-mei=Vitaly kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UenoToshihide en-aut-sei=Ueno en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KojimaShinya en-aut-sei=Kojima en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Honobe-TabuchiAkiko en-aut-sei=Honobe-Tabuchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KawamuraTatsuyoshi en-aut-sei=Kawamura en-aut-mei=Tatsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OhnumaTakehiro en-aut-sei=Ohnuma en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MatsuzawaTakamitsu en-aut-sei=Matsuzawa en-aut-mei=Takamitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KawaharaYu en-aut-sei=Kawahara en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YamashitaKazuo en-aut-sei=Yamashita en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=LinJason en-aut-sei=Lin en-aut-mei=Jason kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KosekiJun en-aut-sei=Koseki en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=NishikawaHiroyoshi en-aut-sei=Nishikawa en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KatoNaoya en-aut-sei=Kato en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ShimamuraTeppei en-aut-sei=Shimamura en-aut-mei=Teppei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MorishitaShinichi en-aut-sei=Morishita en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=SuzukiYutaka en-aut-sei=Suzuki en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=ManoHiroyuki en-aut-sei=Mano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=TorigoeToshihiko en-aut-sei=Torigoe en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=KanasekiTakayuki en-aut-sei=Kanaseki en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawazuMasahito en-aut-sei=Kawazu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Division of Cancer Immunology, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=4 en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=6 en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Computational Biology and Medical Sciences, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Computational Biology and Medical Sciences, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Immunology, Nagoya University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=15 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=16 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=17 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=18 en-affil=Department of Dermatology, Kumamoto Kenhoku Hospital kn-affil= affil-num=19 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=21 en-affil=KOTAI Biotechnologies, Inc kn-affil= affil-num=22 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=23 en-affil=Division of Systems Biology, Nagoya University Graduate School of Medicine kn-affil= affil-num=24 en-affil=Department of Immunology, Nagoya University Graduate School of Medicine kn-affil= affil-num=25 en-affil=Department of Urology, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=26 en-affil=Department of Gastroenterology, Graduate School of Medicine, Chiba University kn-affil= affil-num=27 en-affil=Division of Systems Biology, Nagoya University Graduate School of Medicine kn-affil= affil-num=28 en-affil=Department of Computational Biology and Medical Sciences, The University of Tokyo kn-affil= affil-num=29 en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=30 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=31 en-affil= kn-affil= affil-num=32 en-affil=Division of Cancer Immunology, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=33 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=34 en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=cancer immunology kn-keyword=cancer immunology en-keyword=neoantigen kn-keyword=neoantigen en-keyword=long-read RNA sequencing kn-keyword=long-read RNA sequencing en-keyword=HLA ligandome kn-keyword=HLA ligandome en-keyword=single-cell RNA sequencing kn-keyword=single-cell RNA sequencing en-keyword=single-cell TCR sequencing kn-keyword=single-cell TCR sequencing en-keyword=exhausted T cell kn-keyword=exhausted T cell END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=7 article-no= start-page=102730 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of full-time equivalent allocation on the effectiveness of antimicrobial stewardship activities: A multicenter study in Okayama, Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Optimized administration of antimicrobial agents is critical for mitigating the emergence of antimicrobial resistance. This study aimed to elucidate the relationship between antimicrobial stewardship (AS) activities and antimicrobial prescription trends and patterns.
Methods: This retrospective, multicenter, longitudinal study was conducted between April 2014 and March 2023 (9-year fiscal period). A structured, questionnaire survey, regarding institutional infrastructure and environmental parameters, service modalities provided by AS activities, resource allocation and systemic support, and data on the use of broad-spectrum antimicrobial agents, was distributed to co-investigators working at seven hospitals in Okayama, Japan. Full-time equivalent (FTE) allocation for each healthcare facility were calculated and subsequently compared among the hospitals. Temporal variations in the proportional distribution of broad-spectrum antimicrobial agents were statistically evaluated using joinpoint regression analysis.
Results: Two hospitals where pharmacists were exclusively dedicated to AS activities and met the recommended FTE allocation showed a statistically significant reduction in the proportion of broad-spectrum antibiotic administration, with average annual percentage changes of −8.0 % (95 % confidence interval [CI]: −10.5 to −5.8) and −3.1 % (95 % CI: −5.5 to −0.7), respectively. In contrast, two other hospitals with full-time AS members but insufficient FTE allocation exhibited inconsistent and statistically nonuniform trends. The remaining three healthcare institutions with poorly resourced AS teams demonstrated no statistically significant trends in their broad-spectrum antimicrobial prescriptions.
Conclusion: Our findings uncovered that hospitals with adequate FTE staffing metrics for AS activities exhibited statistically significant downward trends in the consumption of broad-spectrum antimicrobial agents. en-copyright= kn-copyright= en-aut-name=KajitaShiho en-aut-sei=Kajita en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkitaAtsushi en-aut-sei=Okita en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HarukiYuto en-aut-sei=Haruki en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadaHaruto en-aut-sei=Yamada en-aut-mei=Haruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InoueYasurou en-aut-sei=Inoue en-aut-mei=Yasurou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigashionnaTsukasa en-aut-sei=Higashionna en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatouKana en-aut-sei=Satou en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TorigoeFumihiro en-aut-sei=Torigoe en-aut-mei=Fumihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IwamotoShinobu en-aut-sei=Iwamoto en-aut-mei=Shinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshidaMika en-aut-sei=Yoshida en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamaneYumiko en-aut-sei=Yamane en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KenmotsuHiroki en-aut-sei=Kenmotsu en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SugimuraSatoru en-aut-sei=Sugimura en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraYutaka en-aut-sei=Fujiwara en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IkedaFusao en-aut-sei=Ikeda en-aut-mei=Fusao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YoshidaChikamasa en-aut-sei=Yoshida en-aut-mei=Chikamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=AndouShinichirou en-aut-sei=Andou en-aut-mei=Shinichirou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SuwakiToshimitsu en-aut-sei=Suwaki en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Antimicrobial Stewardship Team, Okayama City Hospital kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, Setouchi City Hospital kn-affil= affil-num=4 en-affil=Department of Pharmacy, Tsuyama Chuo Hospital kn-affil= affil-num=5 en-affil=Antimicrobial Stewardship Team, Okayama City Hospital kn-affil= affil-num=6 en-affil=Antimicrobial Stewardship Team, Okayama City Hospital kn-affil= affil-num=7 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=8 en-affil=Division of Pharmacy, Kurashiki Central Hospital kn-affil= affil-num=9 en-affil=Division of Pharmacy, Kurashiki Central Hospital kn-affil= affil-num=10 en-affil=Division of Pharmacy, Okayama Kyoritsu Hospital kn-affil= affil-num=11 en-affil=Infection Control Team, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=12 en-affil=Infection Control Team, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=13 en-affil=Division of Pharmacy, Okayama Saiseikai Hospital kn-affil= affil-num=14 en-affil=Department of Internal Medicine, Okayama Kyoritsu Hospital kn-affil= affil-num=15 en-affil=Infection Control Team, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=16 en-affil=Department of Hepatology, Okayama Saiseikai Hospital kn-affil= affil-num=17 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=18 en-affil=Infection Control Team, Okayama City Hospital kn-affil= affil-num=19 en-affil=Infection Control Team, Okayama City Hospital kn-affil= affil-num=20 en-affil=Infection Control Team, Okayama City Hospital kn-affil= en-keyword=Antimicrobial resistance kn-keyword=Antimicrobial resistance en-keyword=Antimicrobial stewardship kn-keyword=Antimicrobial stewardship en-keyword=Full-time equivalent kn-keyword=Full-time equivalent en-keyword=Infection prevention and control kn-keyword=Infection prevention and control en-keyword=Trend analysis kn-keyword=Trend analysis END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=1713471 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251218 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Regulatory considerations for developing phage therapy medicinal products for the treatment of antimicrobial resistant bacterial infections en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recently, there have been growing expectations that treatment of infections with bacteriophages (phages), viruses which specifically infect bacteria, can be used as a treatment option for antimicrobial resistant bacterial infections. In Europe and the United States, in addition to phage therapy as a form of personalized medicine, development of pre-defined phage therapy medicinal products (PTMPs) is progressing, and clinical trials are underway. From October 2024 to July 2025, the Pharmaceuticals and Medical Devices Agency exchanged opinions on trends and points to consider in drug development of PTMPs used for antimicrobial resistant bacterial infections with external experts. Development of PTMPs for regulatory approval requires quality control strategies, establishment of manufacturing methods, non-clinical evaluations, and clinical trial plans based on the characteristics of the phage. In this document, based on the regulatory and development trends in Europe and the United States, the current considerations on quality, non-clinical evaluation, and clinical trial planning including the Cartagena Act in the development of PTMPs in Japan are summarized. The basic concepts presented here are intended to be applied to antimicrobial resistant bacterial infections targeted by PTMPs but can be mostly applicable to bacterial infections in general. We hope that these findings will further accelerate more active development of PTMPs towards timely patient access to innovative products. en-copyright= kn-copyright= en-aut-name=Fukaya-ShibaAi en-aut-sei=Fukaya-Shiba en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgataAkiko en-aut-sei=Ogata en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuribayashiRyosuke en-aut-sei=Kuribayashi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakuraiAkira en-aut-sei=Sakurai en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiKanako en-aut-sei=Suzuki en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakadamaShunsuke en-aut-sei=Takadama en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishimuraJihei en-aut-sei=Nishimura en-aut-mei=Jihei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhgeHiroki en-aut-sei=Ohge en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakeuchiTakamasa en-aut-sei=Takeuchi en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TamakiHideyuki en-aut-sei=Tamaki en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsumotoTetsuya en-aut-sei=Matsumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KigaKotaro en-aut-sei=Kiga en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwanoHidetomo en-aut-sei=Iwano en-aut-mei=Hidetomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Office of Regulatory Science Coordination, Pharmaceuticals and Medical Devices Agency kn-affil= affil-num=2 en-affil=Office of Regulatory Science Coordination, Pharmaceuticals and Medical Devices Agency kn-affil= affil-num=3 en-affil=Office of Cellular and Tissue-based Products, Pharmaceuticals and Medical Devices Agency kn-affil= affil-num=4 en-affil=Office of Cellular and Tissue-based Products, Pharmaceuticals and Medical Devices Agency kn-affil= affil-num=5 en-affil=Office of Regulatory Science Coordination, Pharmaceuticals and Medical Devices Agency kn-affil= affil-num=6 en-affil=Office of New Drug IV, Pharmaceuticals and Medical Devices Agency kn-affil= affil-num=7 en-affil=Office of New Drug IV, Pharmaceuticals and Medical Devices Agency kn-affil= affil-num=8 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Infectious Diseases, Hiroshima University Hospital kn-affil= affil-num=10 en-affil=Pathogen Genomics Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=11 en-affil=Biomanufacturing Process Research Center, National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=12 en-affil=Department of Infectious Diseases, International University of Health and Welfare kn-affil= affil-num=13 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=14 en-affil=Laboratory of Veterinary Biochemistry, Rakuno Gakuen University School of Veterinary Medicine kn-affil= en-keyword=phage therapy kn-keyword=phage therapy en-keyword=bacteriophage kn-keyword=bacteriophage en-keyword=antimicrobial resistance (AMR) kn-keyword=antimicrobial resistance (AMR) en-keyword=quality considerations kn-keyword=quality considerations en-keyword=non-clinical evaluation kn-keyword=non-clinical evaluation en-keyword=clinical trial plan kn-keyword=clinical trial plan en-keyword=the Cartagena Act kn-keyword=the Cartagena Act END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=29639 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Single cell spatial transcriptomics links Wnt signaling disruption to extracellular matrix development in a cleft palate model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Despite advances in understanding the morphological disruptions that lead to defects in palate formation, the precise perturbations within the signaling microenvironment of palatal clefts remain poorly understood. To explore in greater depth the genomic basis of palatal clefts, we designed and implemented the first single cell spatial RNA-sequencing study in a cleft palate model, utilizing the Pax9−/− murine model at multiple developmental timepoints, which exhibits a consistent cleft palate defect. Visium HD, an emerging platform for true single-cell resolution spatially resolved transcriptomics, was employed using custom bins of 2 × 2 μm spatial gene expression data. Validation of spatial gene expression was then validated using custom designed Xenium In Situ mRNA spatial profiling and RNAscope Multiplex assays. Functional enrichment analysis revealed a palate cell-specific perturbation in Wnt signaling effector function in tandem with disrupted expression of extracellular matrix genes in developing mesenchyme. As a key step toward laying the framework for identifying key molecular targets these data can be used for translational studies aimed at developing effective therapies for human palatal clefts. en-copyright= kn-copyright= en-aut-name=PiñaJeremie Oliver en-aut-sei=Piña en-aut-mei=Jeremie Oliver kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RajuResmi en-aut-sei=Raju en-aut-mei=Resmi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=StipanoEvan en-aut-sei=Stipano en-aut-mei=Evan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MyoAye Chan en-aut-sei=Myo en-aut-mei=Aye Chan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ChattarajParna en-aut-sei=Chattaraj en-aut-mei=Parna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FurukawaMasae en-aut-sei=Furukawa en-aut-mei=Masae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=D’SouzaRena N. en-aut-sei=D’Souza en-aut-mei=Rena N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) kn-affil= affil-num=2 en-affil=Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) kn-affil= affil-num=3 en-affil=Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) kn-affil= affil-num=4 en-affil=Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) kn-affil= affil-num=5 en-affil=Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Department of Molecular Biology and Biochemistry, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Department of Molecular Biology and Biochemistry, Okayama University kn-affil= affil-num=7 en-affil=Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) kn-affil= affil-num=8 en-affil=Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) kn-affil= affil-num=9 en-affil=Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) kn-affil= en-keyword=Spatial biology kn-keyword=Spatial biology en-keyword=Cleft palate kn-keyword=Cleft palate en-keyword=Genomics kn-keyword=Genomics en-keyword=Single cell kn-keyword=Single cell en-keyword=Gene expression kn-keyword=Gene expression en-keyword=Profiling kn-keyword=Profiling en-keyword=Extracellular matrix kn-keyword=Extracellular matrix en-keyword=Wnt kn-keyword=Wnt en-keyword=Transcriptome kn-keyword=Transcriptome END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=12 article-no= start-page=102845 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Whole-genome sequencing and in vitro characterization of a disseminated ST398 Staphylococcus aureus infection: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Staphylococcus aureus potentially causes systemic infections such as disseminated abscesses and bloodstream infections, leading to high mortality rates. We herein describe a case of disseminated muscle abscesses caused by sequence type (ST) 398 methicillin-sensitive S. aureus (MSSA), along with in vitro investigation results for potential pathogenic factors. A 67-year-old healthy woman was admitted to our hospital with complaints of systemic body pain. Blood cultures identified MSSA and contrast-enhanced computed tomography revealed multiple muscle abscesses extending from her neck to her soles. She received antibiotic treatment with intravenous cephazolin and underwent repeated surgical drainage, and was finally discharged. Notably, the MSSA strain exclusively affected her muscle tissues, prompting us to perform genetic analysis to uncover the underlying reason. Short-read genome analysis revealed the isolate to be ST398, harboring chp and scn genes known for immune evasion from human immunity. However, no other known pathogenic factors were identified despite rigorous assays for biofilm formation, surface and cell wall proteins, protease production, and hyaluronidase activity. ST398 S. aureus is commonly isolated from livestock, and her prior experience of being flooded could be related to the disease onset. The present case underscores the possibility of severe ST398 MSSA infections in humans, even in the absence of direct animal exposure. en-copyright= kn-copyright= en-aut-name=SazumiYosuke en-aut-sei=Sazumi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatoAtsushi en-aut-sei=Kato en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuyamaAtsuhito en-aut-sei=Suyama en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KutsunoShoko en-aut-sei=Kutsuno en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HisatsuneJunzo en-aut-sei=Hisatsune en-aut-mei=Junzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugaiMotoyuki en-aut-sei=Sugai en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Bacteriology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=9 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=10 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=11 en-affil=Department of Bacteriology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Staphylococcus aureus kn-keyword=Staphylococcus aureus en-keyword=Sequence type 398 kn-keyword=Sequence type 398 en-keyword=Disseminated infection kn-keyword=Disseminated infection en-keyword=Immune evasion cluster gene kn-keyword=Immune evasion cluster gene END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251229 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genotype–Phenotype Correlations of Li–Fraumeni Syndrome in Japan Children's Cancer Group LFS20 Study Cohort en-subtitle= kn-subtitle= en-abstract= kn-abstract=Li–Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by germline pathogenic variants in the TP53 gene. With the increasing use of multi-gene panel testing, TP53 variants have been identified in individuals who do not meet established TP53 testing criteria, such as the Chompret criteria. The term “attenuated LFS” has been proposed for some of these cases, particularly those with adult-onset cancer. We analyzed participants of the Japanese nationwide prospective clinical trial of the cancer surveillance program (Japan Children's Cancer Group LFS-20), along with clinical information including their family histories, to better understand their genotypic and phenotypic characteristics. We identified 32 distinct TP53 variants from 41 families (45 participants), including four missense variants with conflicting classifications of pathogenicity in ClinVar. Among these families, 36 (88%) met the LFS criteria (hereafter referred to as “LFS” in contrast to attenuated LFS), while 5 (12%) were classified as attenuated LFS. Including 30 additional family members carrying the same variant, we analyzed 75 individuals with TP53 variants. Of these, 40 with LFS and 6 with attenuated LFS had cancer. Multiple primary cancers occurred in 22 individuals (21 LFS, 1 attenuated LFS). LFS-core tumors accounted for 66% (58/88) of cancers in the LFS group and 63% (5/8) in the attenuated LFS group; of note, all core tumors in the attenuated group were limited to breast cancer. Hotspot missense variants were detected in 11 of 36 LFS families and in none of 5 attenuated LFS families, and non-hotspot null variants were found in 14 and 1, respectively. Our study revealed genotype–phenotype correlations in several respects. UMIN-CTR: UMIN000045855. en-copyright= kn-copyright= en-aut-name=YamazakiFumito en-aut-sei=Yamazaki en-aut-mei=Fumito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakanoYoshiko en-aut-sei=Nakano en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SanadaMasashi en-aut-sei=Sanada en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KurahashiHiroki en-aut-sei=Kurahashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyaiShunsuke en-aut-sei=Miyai en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UekiArisa en-aut-sei=Ueki en-aut-mei=Arisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeYuko en-aut-sei=Watanabe en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HasegawaDaisuke en-aut-sei=Hasegawa en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KarakawaShuhei en-aut-sei=Karakawa en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SaitoAkiko M. en-aut-sei=Saito en-aut-mei=Akiko M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=InoueEisuke en-aut-sei=Inoue en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatoMotohiro en-aut-sei=Kato en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HattoriHiroyoshi en-aut-sei=Hattori en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Pediatrics, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Department of Genetic Medicine and Services, National Cancer Center Hospital kn-affil= affil-num=3 en-affil=Department of Advanced Diagnosis, Clinical Research Center, NHO Nagoya Medical Center kn-affil= affil-num=4 en-affil=Division of Molecular Genetics, Center for Medical Science, Fujita Health University kn-affil= affil-num=5 en-affil=Division of Molecular Genetics, Center for Medical Science, Fujita Health University kn-affil= affil-num=6 en-affil=Department of Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=7 en-affil=Department of Pediatric Oncology, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Pediatrics, St. Luke's International Hospital kn-affil= affil-num=9 en-affil=Department of Pediatrics, Hiroshima University Hospital kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Clinical Research Center, NHO Nagoya Medical Center kn-affil= affil-num=13 en-affil=Showa Medical University Research Administration Center, Showa Medical University kn-affil= affil-num=14 en-affil=Department of Pediatrics, The University of Tokyo kn-affil= affil-num=15 en-affil=Department of Clinical Genetics, NHO Nagoya Medical Center kn-affil= en-keyword=cancer predisposition kn-keyword=cancer predisposition en-keyword=genotype–phenotype correlations kn-keyword=genotype–phenotype correlations en-keyword=hotspot variants kn-keyword=hotspot variants en-keyword=Li–Fraumeni syndrome kn-keyword=Li–Fraumeni syndrome en-keyword=TP53 kn-keyword=TP53 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Atezolizumab + Chemotherapy for Advanced Non-Small Cell Lung Cancer in Japanese Clinical Practice (J-TAIL-2) en-subtitle= kn-subtitle= en-abstract= kn-abstract=First-line atezolizumab combination therapies were approved for the treatment of metastatic non-small cell lung cancer (NSCLC) based on results from the global phase 3 trials IMpower130, IMpower132, and IMpower150. These trials reported 12-month overall survival (OS) rates of 60%–67% with atezolizumab combination therapy. J-TAIL-2 (NCT04501497), a prospective, multicenter, observational study, evaluated atezolizumab combination therapy in routine clinical practice in Japan. Patients ≥ 20 years old with NSCLC received atezolizumab plus carboplatin and nab-paclitaxel (atezo + CnP), atezolizumab plus carboplatin or cisplatin plus pemetrexed (atezo + PP), or atezolizumab plus bevacizumab plus carboplatin and paclitaxel (atezo + bev + CP) in clinical practice. The primary endpoint was the 12-month OS rate. Secondary endpoints included OS, progression-free survival, and subgroup analyses, including IMpower-unlike (did not meet the main eligibility criteria of each IMpower trial) and IMpower-like patients. In total, 814 patients were enrolled (atezo + CnP, n = 217; atezo + PP, n = 211; atezo + bev + CP, n = 386). The IMpower-unlike group included patients with Eastern Cooperative Oncology Group performance status ≥ 2, autoimmune disease, or interstitial lung disease. Twelve-month OS rates (95% confidence interval [CI]) were 62.9% (55.8–69.2), 72.1% (65.2–77.9), and 68.3% (63.2–72.9) with atezo + CnP, atezo + PP, and atezo + bev + CP, respectively. OS hazard ratios (95% CI) in the IMpower-unlike vs. -like subgroups were 1.36 (0.91–2.05), 1.08 (0.70–1.68), and 1.49 (1.09–2.06), respectively. No new safety signals were observed. Real-world efficacy and safety for each atezolizumab combination were comparable to those in the relevant IMpower trials. en-copyright= kn-copyright= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishioMakoto en-aut-sei=Nishio en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OsoegawaAtsushi en-aut-sei=Osoegawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuchiEiki en-aut-sei=Kikuchi en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KimuraHideharu en-aut-sei=Kimura en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GotoYasushi en-aut-sei=Goto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuJunichi en-aut-sei=Shimizu en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyauchiEisaku en-aut-sei=Miyauchi en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshinoIchiro en-aut-sei=Yoshino en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MisumiToshihiro en-aut-sei=Misumi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WatanabeYasutaka en-aut-sei=Watanabe en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HataAkito en-aut-sei=Hata en-aut-mei=Akito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KisoharaAkira en-aut-sei=Kisohara en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamaguchiMasafumi en-aut-sei=Yamaguchi en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MiwaAsako en-aut-sei=Miwa en-aut-mei=Asako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IwasawaShunichiro en-aut-sei=Iwasawa en-aut-mei=Shunichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TanakaMisa en-aut-sei=Tanaka en-aut-mei=Misa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=GemmaAkihiko en-aut-sei=Gemma en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, Kansai Medical University kn-affil= affil-num=2 en-affil=Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Kanazawa University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Thoracic Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Tohoku University Hospital kn-affil= affil-num=10 en-affil=International University of Health and Welfare, Narita Hospital kn-affil= affil-num=11 en-affil=Department of Data Science, National Cancer Center Hospital East kn-affil= affil-num=12 en-affil=Department of Thoracic Oncology, Saitama Cancer Center kn-affil= affil-num=13 en-affil=Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Kasukabe Medical Center kn-affil= affil-num=15 en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center kn-affil= affil-num=16 en-affil=Department of Thoracic Oncology, NHO Kyushu Cancer Center kn-affil= affil-num=17 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=18 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=19 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=20 en-affil=Nippon Medical School kn-affil= en-keyword=atezolizumab kn-keyword=atezolizumab en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=lung cancer kn-keyword=lung cancer en-keyword=non-small cell kn-keyword=non-small cell en-keyword=observational kn-keyword=observational END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250923 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hospital-acquired pneumonia caused by multidrug-resistant Streptococcus pneumoniae serotype 15A en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Streptococcus pneumoniae remains a common cause of community-acquired pneumonia but is an infrequent pathogen in hospital-acquired pneumonia (HAP). Non-vaccine serotypes of multidrug-resistant (MDR) S. pneumoniae strains have been emerging globally, posing an increased risk of nosocomial infection.
Case A 71 year-old man developed pneumonia on postoperative day 4 following spinal fusion surgery. Despite initial treatment with ampicillin/sulbactam, his condition deteriorated, requiring ICU admission and mechanical ventilation. Microbiological testing confirmed S. pneumoniae as a causative pathogen, and ceftriaxone was empirically administered based on the local antibiogram. However, antimicrobial susceptibility testing revealed resistant profiles to penicillin (minimum inhibitory concentration [MIC], 8 µg/mL), ceftriaxone (MIC, 16 µg/mL), meropenem (MIC, 1 µg/mL), macrolides, and clindamycin, while demonstrating susceptibility to levofloxacin and vancomycin. The therapeutic regimen was subsequently adjusted to levofloxacin, resulting in clinical improvement. The isolate was later identified as serotype 15A, sequence type 63 (ST63).
Conclusion This case highlights that MDR S. pneumoniae can cause early-onset HAP and may not be covered by standard empiric therapies, emphasizing the need for careful evaluation of treatment response. Continued surveillance of infections caused by vaccine-escape clones like MDR serotype 15A is essential, given their increasing clinical relevance. en-copyright= kn-copyright= en-aut-name=AkazawaHidemasa en-aut-sei=Akazawa en-aut-mei=Hidemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamotoKenta en-aut-sei=Nakamoto en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimbeMadoka en-aut-sei=Shimbe en-aut-mei=Madoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ChangBin en-aut-sei=Chang en-aut-mei=Bin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AkedaYukihiro en-aut-sei=Akeda en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=7 en-affil=Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Antimicrobial resistance kn-keyword=Antimicrobial resistance en-keyword=Multidrug-resistant kn-keyword=Multidrug-resistant en-keyword=Nosocomial infection kn-keyword=Nosocomial infection en-keyword=Sequence type 63 kn-keyword=Sequence type 63 en-keyword=Serotype 15A kn-keyword=Serotype 15A en-keyword=Streptococcus pneumoniae kn-keyword=Streptococcus pneumoniae END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=376 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oral Health-Related Quality of Life and Self-Reported Oral Health Status Are Associated with Change in Self-Reported Depression Status: A Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Oral health-related quality of life (OHRQoL) may influence mental health outcomes, yet longitudinal evidence on its association with depression remains limited. This study aimed to examine whether oral health status and OHRQoL are associated with a change in self-reported depression status among adults in Japan. Methods: We analyzed data from the Japan COVID-19 and Society Internet Survey (JACSIS), conducted in 2022 and 2023. A total of 15,068 participants aged ≥20 years without depression at baseline were included. Depression status was identified by self-reported measures between the two survey waves. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for change in self-reported depression status in relation to OHRQoL and oral health status, adjusting for sociodemographic and behavioral factors. Results: During follow-up, 218 participants (1.45%) reported a change in self-reported depression status. Poorer OHRQoL was significantly associated with a change in self-reported depression status (OR: 1.018; 95% CI: 1.001–1.036; p = 0.039). Additional risk factors included younger age (OR: 0.974; 95% CI: 0.964–0.985), participation in hobbies and cultural activities (OR: 2.224; 95% CI: 1.498–3.302), habitual use of sleeping pills or anxiolytics (current use OR: 3.512; 95% CI: 2.267–5.442), increased loneliness (OR: 1.217; 95% CI: 1.140–1.299), lower life satisfaction (OR: 0.900; 95% CI: 0.836–0.969), and poor self-rated health (OR: 2.921; 95% CI: 1.810–4.715). Conclusions: Impaired OHRQoL was associated with a change in self-reported depression status, potentially through psychosocial mechanisms. These findings suggest that oral health and OHRQoL may be relevant factors to consider in integrated oral and mental health approaches in clinical practice. en-copyright= kn-copyright= en-aut-name=TakeuchiNoriko en-aut-sei=Takeuchi en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaruyamaTakayuki en-aut-sei=Maruyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ToyamaNaoki en-aut-sei=Toyama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsubeYuzuki en-aut-sei=Katsube en-aut-mei=Yuzuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TabuchiTakahiro en-aut-sei=Tabuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Division of Dentistry, Medical Development Field, Okayama University kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Dental School, Okayama University kn-affil= affil-num=5 en-affil=Division of Epidemiology, School of Public Health, Tohoku University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=oral health-related quality of life kn-keyword=oral health-related quality of life en-keyword=depression status kn-keyword=depression status en-keyword=cohort study kn-keyword=cohort study END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue= article-no= start-page=100857 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A multi-institutional dummy run on segmentation variability and plan quality of stereotactic body radiotherapy for oligometastatic disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and purpose: Oligometastatic disease represents limited metastatic burden, and local ablative therapies such as stereotactic body radiotherapy (SBRT) may improve survival. However, inter-institutional variability in target segmentation and treatment planning can compromise treatment quality. This study aimed to evaluate the segmentation variability and dose distribution quality of SBRT in oligometastatic settings using a multi-institutional dummy run approach.
Methods and materials: Sixty-nine institutions were provided with two anonymized cases of adrenal and spine metastases to delineate targets and organs at risk (OARs) and create intensity-modulated radiotherapy plans following a protocol. Variability was quantified using the Dice similarity coefficient (DSC), Hausdorff distance, and mean distance to agreement. Plan qualities were assessed using the Paddick conformity index, modified gradient index, and a new three-dimensional conformity–gradient index (3D-CGI). Knowledge-based planning (KBP) was applied to explore potential improvements in OAR sparing.
Results: All submitted plans met protocol dose constraints. However, substantial segmentation variability was observed, particularly for the spine case. Among 136 plans, 79% demonstrated acceptable conformity and dose gradients, with 3D-CGI < 6 correlating with favorable distributions. Mean DSC was 0.93 for the clinical target volume and 0.76 for the cauda equina, which showed the highest variability. KBP reduced OAR doses for the adrenal case but showed limited impact for the spine case.
Conclusions: Although dose constraints were achieved, segmentation variability remained substantial, particularly for the cauda equina in the spine case. These findings emphasize inter-institutional differences and the need for standardization and tools to improve SBRT consistency. en-copyright= kn-copyright= en-aut-name=HirashimaHideaki en-aut-sei=Hirashima en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuoYukinori en-aut-sei=Matsuo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshikuraSatoshi en-aut-sei=Ishikura en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamuraMitsuhiro en-aut-sei=Nakamura en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishibuchiIkuno en-aut-sei=Nishibuchi en-aut-mei=Ikuno kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawaharaDaisuke en-aut-sei=Kawahara en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimadaYoshihisa en-aut-sei=Shimada en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakaharaYoshiro en-aut-sei=Nakahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishioTeiji en-aut-sei=Nishio en-aut-mei=Teiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShikamaNaoto en-aut-sei=Shikama en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WatanabeShun-ichi en-aut-sei=Watanabe en-aut-mei=Shun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkamotoIsamu en-aut-sei=Okamoto en-aut-mei=Isamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshibaToshiyuki en-aut-sei=Ishiba en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MizowakiTakashi en-aut-sei=Mizowaki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University kn-affil= affil-num=2 en-affil=Department of Radiation Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Radiation Oncology, St. Luke’s International Hospital, St. Luke’s International University kn-affil= affil-num=4 en-affil=Department of Advanced Medical Physics, Graduate School of Medicine, Kyoto University kn-affil= affil-num=5 en-affil=Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University kn-affil= affil-num=6 en-affil=Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University kn-affil= affil-num=7 en-affil=Department of Surgery, Tokyo Medical University kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Kitasato University Hospital kn-affil= affil-num=9 en-affil=Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka kn-affil= affil-num=10 en-affil=Department of Radiation Oncology, Juntendo University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Thoracic Surgery, National Cancer Center Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=13 en-affil=Department of Breast Surgery, Institute of Science Tokyo kn-affil= affil-num=14 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=15 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University kn-affil= en-keyword=Oligometastatic disease kn-keyword=Oligometastatic disease en-keyword=Dummy run kn-keyword=Dummy run en-keyword=Segmentation variability kn-keyword=Segmentation variability en-keyword=Dose distribution accuracy kn-keyword=Dose distribution accuracy END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=3 article-no= start-page=118 end-page=125 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The results of COVID-19 antibody testing studies in Bizen, Japan kn-title=備前市における新型コロナウイルス感染症の抗体検査に関する研究の成果報告 en-subtitle= kn-subtitle= en-abstract= kn-abstract= We conducted two prospective cohort studies (June 2022–March 2023 and Nov 2023–Jan 2024) of 1,899 and 445 residents and other individuals who are affiliated with institutions in the city of Bizen in Japan's Okayama prefecture (population 32,320 as of 2020). We measured the subjects' titers of antibodies against SARS-CoV-2, evaluated changes in their antibody titers, and assessed the associations of the titers with the subjects' vaccination status, infection, and COVID-19 status/severity. This report summarizes the two studies' findings. These prospective studies based on a wide age range in a general population provide information that can be used to determine the appropriate timing of vaccination during a pandemic. en-copyright= kn-copyright= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name=頼藤貴志 kn-aut-sei=頼藤 kn-aut-mei=貴志 aut-affil-num=1 ORCID= en-aut-name=SasakiAyako en-aut-sei=Sasaki en-aut-mei=Ayako kn-aut-name=佐々木綾子 kn-aut-sei=佐々木 kn-aut-mei=綾子 aut-affil-num=2 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name=松本尚美 kn-aut-sei=松本 kn-aut-mei=尚美 aut-affil-num=3 ORCID= en-aut-name=KadowakiTomoka en-aut-sei=Kadowaki en-aut-mei=Tomoka kn-aut-name=門脇知花 kn-aut-sei=門脇 kn-aut-mei=知花 aut-affil-num=4 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name=三橋利晴 kn-aut-sei=三橋 kn-aut-mei=利晴 aut-affil-num=5 ORCID= en-aut-name=TakaoSoshi en-aut-sei=Takao en-aut-mei=Soshi kn-aut-name=高尾総司 kn-aut-sei=高尾 kn-aut-mei=総司 aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil=岡山大学学術研究院医歯薬学域 疫学・衛生学 affil-num=2 en-affil=Kurashiki City Public Health Center kn-affil=倉敷市保健所 affil-num=3 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil=岡山大学学術研究院医歯薬学域 疫学・衛生学 affil-num=4 en-affil=Center for Public Health Action in Applied Epidemiology, National Institute of Infectious Diseases kn-affil=国立感染症研究所 応用疫学研究センター affil-num=5 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil=岡山大学病院 新医療研究開発センター affil-num=6 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil=岡山大学学術研究院医歯薬学域 疫学・衛生学 en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=ワクチン (vaccination) kn-keyword=ワクチン (vaccination) en-keyword=抗体価 (antibody titer) kn-keyword=抗体価 (antibody titer) en-keyword=感染 (infection) kn-keyword=感染 (infection) END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=1 article-no= start-page=25 end-page=38 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Near-infrared Photoimmunotherapy Targeting High-risk Human Neuroblastoma Cells Expressing GD2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system in infancy. Despite advances in treatment, the prognosis remains poor for high-risk NB patients. Although immunotherapy using anti-GD2 antibodies is available for high-risk NB, the therapeutic efficacy is insufficient. Near-infrared photoimmunotherapy (NIR-PIT) is an antitumor strategy that induces tumor-specific cytotoxicity by combining an antibody-photoabsorber conjugate (APC) with NIR light irradiation. In this study, we investigated the therapeutic efficacy of GD2-targeted NIR-PIT against human NB cells.
Materials and Methods: GD2 expression was analyzed on the surface of high-risk human NB cells (CHP-134, LA-N-5, IMR-32) and non-high-risk human NB cells (SK-N-SH) by flow cytometry. The APC was synthesized by incubating anti-GD2 antibody and IR700. The cytotoxic effect of GD2-targeted NIR-PIT was evaluated using the XTT assay. The distribution of dead cells within tumor spheres was evaluated using a live/dead assay. The in vivo antitumor effect of GD2-targeted NIR-PIT was assessed using a subcutaneous human NB xenograft tumor model.
Results: GD2 protein was expressed on the surface of CHP-134, LA-N-5, and IMR-32 cells but not SK-N-SH cells. GD2-targeted NIR-PIT significantly suppressed the viability of GD2-positive NB cells but not GD2-negative NB cells, compared to the control and monotherapy groups. GD2-targeted NIR-PIT significantly reduced the volume of GD2-positive CHP-134 tumor spheres by inducing the accumulation of dead cells. Subcutaneous CHP-134 xenograft tumor models demonstrated that GD2-targeted NIR-PIT significantly inhibited tumor growth compared with the control and monotherapy groups.
Conclusion: GD2-targeted NIR-PIT is a promising antitumor strategy for treating high-risk NB tumors expressing GD2. en-copyright= kn-copyright= en-aut-name=NOUSOHIROSHI en-aut-sei=NOUSO en-aut-mei=HIROSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TAZAWAHIROSHI en-aut-sei=TAZAWA en-aut-mei=HIROSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TANIMOTOTERUTAKA en-aut-sei=TANIMOTO en-aut-mei=TERUTAKA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TANIMORIMICHI en-aut-sei=TANI en-aut-mei=MORIMICHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WATANABEHINAKO en-aut-sei=WATANABE en-aut-mei=HINAKO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OYAMATAKANORI en-aut-sei=OYAMA en-aut-mei=TAKANORI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NOMAKAZUHIRO en-aut-sei=NOMA en-aut-mei=KAZUHIRO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KAGAWASHUNSUKE en-aut-sei=KAGAWA en-aut-mei=SHUNSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KOBAYASHIHISATAKA en-aut-sei=KOBAYASHI en-aut-mei=HISATAKA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NODATAKUO en-aut-sei=NODA en-aut-mei=TAKUO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KURODASHINJI en-aut-sei=KURODA en-aut-mei=SHINJI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FUJIWARATOSHIYOSHI en-aut-sei=FUJIWARA en-aut-mei=TOSHIYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health kn-affil= affil-num=10 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Neuroblastoma kn-keyword=Neuroblastoma en-keyword=GD2 kn-keyword=GD2 en-keyword=near-infrared photoimmunotherapy kn-keyword=near-infrared photoimmunotherapy en-keyword=IR700 kn-keyword=IR700 END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=RP99936 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250811 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Redistribution of fragmented mitochondria ensures symmetric organelle partitioning and faithful chromosome segregation in mitotic mouse zygotes en-subtitle= kn-subtitle= en-abstract= kn-abstract=In cleavage-stage embryos, preexisting organelles partition evenly into daughter blastomeres without significant cell growth after symmetric cell division. The presence of mitochondrial DNA within mitochondria and its restricted replication during preimplantation development makes their inheritance particularly important. While chromosomes are precisely segregated by the mitotic spindle, the mechanisms controlling mitochondrial partitioning remain poorly understood. In this study, we investigate the mechanism by which Dynamin-related protein 1 (Drp1) controls the mitochondrial redistribution and partitioning during embryonic cleavage. Depletion of Drp1 in mouse zygotes causes marked mitochondrial aggregation, and the majority of embryos arrest at the 2 cell stage. Clumped mitochondria are located in the center of mitotic Drp1-depleted zygotes with less uniform distribution, thereby preventing their symmetric partitioning. Asymmetric mitochondrial inheritance is accompanied by functionally inequivalent blastomeres with biased ATP and endoplasmic reticulum Ca2+ levels. We also find that marked mitochondrial centration in Drp1-depleted zygotes prevents the assembly of parental chromosomes, resulting in chromosome segregation defects and binucleation. Thus, mitochondrial fragmentation mediated by Drp1 ensures proper organelle positioning and partitioning into functional daughters during the first embryonic cleavage. en-copyright= kn-copyright= en-aut-name=GekkoHaruna en-aut-sei=Gekko en-aut-mei=Haruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomuraRuri en-aut-sei=Nomura en-aut-mei=Ruri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuzuharaDaiki en-aut-sei=Kuzuhara en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KaneyasuMasato en-aut-sei=Kaneyasu en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KosekiGenpei en-aut-sei=Koseki en-aut-mei=Genpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AdhikariDeepak en-aut-sei=Adhikari en-aut-mei=Deepak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MioYasuyuki en-aut-sei=Mio en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CarrollJohn en-aut-sei=Carroll en-aut-mei=John kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KonoTomohiro en-aut-sei=Kono en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FunahashiHiroaki en-aut-sei=Funahashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WakaiTakuya en-aut-sei=Wakai en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Animal Science, Graduate School of Environment and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Animal Science, Graduate School of Environment and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Reproductive Centre, Mio Fertility Clinic kn-affil= affil-num=4 en-affil=Department of Animal Science, Graduate School of Environment and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Animal Science, Graduate School of Environment and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Development and Stem Cell Program and Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University kn-affil= affil-num=7 en-affil=Reproductive Centre, Mio Fertility Clinic kn-affil= affil-num=8 en-affil=Development and Stem Cell Program and Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University kn-affil= affil-num=9 en-affil=Department of Bioscience, Tokyo University of Agriculture kn-affil= affil-num=10 en-affil=Department of Animal Science, Graduate School of Environment and Life Science, Okayama University kn-affil= affil-num=11 en-affil=Department of Animal Science, Graduate School of Environment and Life Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=24 article-no= start-page=e195776 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251222 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enhancement of drug delivery through fibroblast activation protein–targeted near-infrared photoimmunotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=The tumor microenvironment plays a key role in cancer progression and therapy resistance, with cancer-associated fibroblasts (CAFs) contributing to desmoplasia, extracellular matrix (ECM) remodeling, and elevated interstitial fluid pressure, all of which hinder drug delivery. We investigated fibroblast activation protein–targeted (FAP-targeted) near-infrared photoimmunotherapy (NIR-PIT) as a strategy to improve drug penetration in CAF-rich tumors. In clinical esophageal cancer samples, FAP expression strongly correlated with increased collagen I, hyaluronic acid, and microvascular collapse. CAF-rich 3D spheroids demonstrated elevated ECM deposition and significantly impaired drug uptake compared with CAF-poor models. FAP-targeted NIR-PIT selectively reduced CAFs, reduced ECM components, and restored drug permeability. In vivo, FAP-targeted NIR-PIT enhanced the accumulation of panitumumab and Abraxane in CAF-rich tumors and improved antitumor efficacy when combined with chemotherapy. These findings highlight FAP-targeted NIR-PIT as a promising therapeutic approach to remodel the tumor stroma and overcome drug resistance in desmoplastic solid tumors. en-copyright= kn-copyright= en-aut-name=NishimuraSeitaro en-aut-sei=Nishimura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoTasuku en-aut-sei=Matsumoto en-aut-mei=Tasuku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakedaYasushige en-aut-sei=Takeda en-aut-mei=Yasushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiTatsuya en-aut-sei=Takahashi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoHijiri en-aut-sei=Matsumoto en-aut-mei=Hijiri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawasakiKento en-aut-sei=Kawasaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KunitomoTomoyoshi en-aut-sei=Kunitomo en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkaiMasaaki en-aut-sei=Akai en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KobayashiTeruki en-aut-sei=Kobayashi en-aut-mei=Teruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NishiwakiNoriyuki en-aut-sei=Nishiwaki en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KashimaHajime en-aut-sei=Kashima en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatoTakuya en-aut-sei=Kato en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ChoykePeter L. en-aut-sei=Choyke en-aut-mei=Peter L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KobayashiHisataka en-aut-sei=Kobayashi en-aut-mei=Hisataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=17 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=20 en-affil=Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIH kn-affil= affil-num=21 en-affil=Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIH kn-affil= affil-num=22 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251117 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genomic Profiling of Pediatric Solid Tumors With a Dual DNA/RNA Panel: JCCG-TOP2 Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=To develop an optimized genomic medicine platform for pediatric cancers, a nationwide cancer genome profiling project was conducted from January 2022 to February 2023 in collaboration with the Japan Children's Cancer Group. This prospective observational study analyzed matched blood and FFPE tumor samples from patients aged 0–29 years with solid tumors. Genomic analysis used the TOP2 hybrid capture–enrichment system, targeting 737 and 455 genes in the DNA and RNA panels, along with allele-specific genome copy number alterations. A total of 210 patients from 50 institutions were enrolled across Japan (median age, 8 years; range, 0–25). Of these, 154 (77%) were enrolled at diagnosis or during/after initial treatment and 56 (27%) at disease progression or relapse. The TOP2 findings had great benefits in clarifying the diagnosis of pediatric solid tumors. Among the 204 patients with genomic results, 147 (72%) had potentially actionable findings, including diagnostic, prognostic, and therapeutic findings in 111 (54%), 61 (30%), and 64 (31%), respectively. Oncogenic fusions were noted in 45 (23%) patients. A copy number alteration was identified in at least one genomic region in 170 (83%) patients. Two patients exhibited a high tumor mutation burden. Seventeen (8%) patients harbored a germline pathogenic/likely pathogenic variant in cancer-predisposing genes. This study highlighted the feasibility of implementing a nationwide precision medicine platform and the clinical utility of the TOP2 system for pediatric cancers. The results support the integration of genomic data into the standard clinical care of pediatric patients with cancer, both at diagnosis and at relapse. en-copyright= kn-copyright= en-aut-name=TaoKayoko en-aut-sei=Tao en-aut-mei=Kayoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshiokaTakako en-aut-sei=Yoshioka en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatoMiho en-aut-sei=Kato en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KomatsuKazuyuki en-aut-sei=Komatsu en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujimotoShinichi en-aut-sei=Tsujimoto en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakamotoKenichi en-aut-sei=Sakamoto en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanimuraKazuki en-aut-sei=Tanimura en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiyamaMinako en-aut-sei=Sugiyama en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SekiguchiMasahiro en-aut-sei=Sekiguchi en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakanoYoshiko en-aut-sei=Nakano en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YatabeYasushi en-aut-sei=Yatabe en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YoshidaAkihiko en-aut-sei=Yoshida en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OkitaHajime en-aut-sei=Okita en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HiratoJunko en-aut-sei=Hirato en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KohashiKenichi en-aut-sei=Kohashi en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TanakaYukichi en-aut-sei=Tanaka en-aut-mei=Yukichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KohsakaShinji en-aut-sei=Kohsaka en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KuboTakashi en-aut-sei=Kubo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SunamiKuniko en-aut-sei=Sunami en-aut-mei=Kuniko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HirataMakoto en-aut-sei=Hirata en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=TsutsumiShuichi en-aut-sei=Tsutsumi en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=AburataniHiroyuki en-aut-sei=Aburatani en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KohKatsuyoshi en-aut-sei=Koh en-aut-mei=Katsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=HirayamaMasahiro en-aut-sei=Hirayama en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KarakawaShuhei en-aut-sei=Karakawa en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TerashitaYukayo en-aut-sei=Terashita en-aut-mei=Yukayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=FujisakiHiroyuki en-aut-sei=Fujisaki en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=YagiTakeshi en-aut-sei=Yagi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=YonedaAkihiro en-aut-sei=Yoneda en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=MochizukiShinji en-aut-sei=Mochizuki en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=ShichinoHiroyuki en-aut-sei=Shichino en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=SuzukiTatsuya en-aut-sei=Suzuki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=TakimotoTetsuya en-aut-sei=Takimoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=IchimuraKoichi en-aut-sei=Ichimura en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=OgawaChitose en-aut-sei=Ogawa en-aut-mei=Chitose kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=MatsumotoKimikazu en-aut-sei=Matsumoto en-aut-mei=Kimikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=IchikawaHitoshi en-aut-sei=Ichikawa en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=KatoMotohiro en-aut-sei=Kato en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= affil-num=1 en-affil=Department of Pediatrics, National Cancer Center Hospital kn-affil= affil-num=2 en-affil=Department of Pathology, National Center for Child Health and Development kn-affil= affil-num=3 en-affil=Department of Childhood Cancer Data Management, National Center for Child Health and Development kn-affil= affil-num=4 en-affil=Department of Pediatrics, Hamamatsu University School of Medicine kn-affil= affil-num=5 en-affil=Department of Pediatrics, Yokohama City University kn-affil= affil-num=6 en-affil=Department of Pediatrics, Shinshu University School of Medicine kn-affil= affil-num=7 en-affil=Department of Pediatrics, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Pediatrics, National Cancer Center Hospital kn-affil= affil-num=9 en-affil=Department of Pediatrics, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Pediatrics, The University of Tokyo kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Diagnostic Pathology, National Cancer Center Hospital kn-affil= affil-num=13 en-affil=Department of Diagnostic Pathology, National Cancer Center Hospital kn-affil= affil-num=14 en-affil=Department of Pathology, Keio University School of Medicine kn-affil= affil-num=15 en-affil=Department of Pathology, Public Tomioka General Hospital kn-affil= affil-num=16 en-affil=Department of Pathology, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=17 en-affil=Department of Pathology, Kanagawa Children's Medical Center kn-affil= affil-num=18 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=19 en-affil=Department of Clinical Genomics, National Cancer Center Research Institute kn-affil= affil-num=20 en-affil=Department of Laboratory Medicine, National Cancer Center Hospital kn-affil= affil-num=21 en-affil=Department of Genetic Medicine and Services, National Cancer Center Hospital kn-affil= affil-num=22 en-affil=Genome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of Tokyo kn-affil= affil-num=23 en-affil=Genome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of Tokyo kn-affil= affil-num=24 en-affil=Department of Hematology and Oncology, Saitama Children's Medical Center kn-affil= affil-num=25 en-affil=Department of Pediatrics, Mie University Graduate School of Medicine kn-affil= affil-num=26 en-affil=Department of Pediatrics, Hiroshima University Hospital kn-affil= affil-num=27 en-affil=Department of Pediatrics, Hokkaido University Hospital kn-affil= affil-num=28 en-affil=Department of Pediatric Hematology and Oncology, Osaka City General Hospital kn-affil= affil-num=29 en-affil=Okinawa Prefectural Nanbu Medical Center & Children's Medical Center kn-affil= affil-num=30 en-affil=Department of Pediatric Surgery, National Center for Child Health and Development kn-affil= affil-num=31 en-affil=Department of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health Security kn-affil= affil-num=32 en-affil=Department of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health Security kn-affil= affil-num=33 en-affil=Department of Hematology, National Cancer Center Hospital kn-affil= affil-num=34 en-affil=Department of Childhood Cancer Data Management, National Center for Child Health and Development kn-affil= affil-num=35 en-affil=Department of Pathology, Kyorin University Faculty of Medicine kn-affil= affil-num=36 en-affil=Department of Pediatrics, National Cancer Center Hospital kn-affil= affil-num=37 en-affil=Children's Cancer Center National Center for Child Health and Development kn-affil= affil-num=38 en-affil=Department of Clinical Genomics, National Cancer Center Research Institute kn-affil= affil-num=39 en-affil=Department of Pediatrics, The University of Tokyo kn-affil= en-keyword=genomic medicine kn-keyword=genomic medicine en-keyword=integrative diagnosis kn-keyword=integrative diagnosis en-keyword=molecularly targeted therapy kn-keyword=molecularly targeted therapy en-keyword=multigene panel kn-keyword=multigene panel en-keyword=pediatric cancers kn-keyword=pediatric cancers END start-ver=1.4 cd-journal=joma no-vol=53 cd-vols= no-issue=22 article-no= start-page=gkaf1322 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=eIF2D promotes 40S ribosomal subunit recycling during intrinsic ribosome destabilization en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although eukaryotic initiation factor 2D (eIF2D) is implicated in translation initiation, reinitiation, and ribosome recycling, its precise role remains unclear. Here, we show that eIF2D promotes 40S ribosome recycling during intrinsic ribosome destabilization (IRD), a process in which ribosomes stochastically destabilize while translating proteins with consecutive acidic amino acids at their NH2-terminus. Unrecycled 40S ribosomes accumulate in eIF2D-deficient cells, leading to 80S ribosome stalling. Selective translation complex profiling (TCP-seq) reveals that eIF2D preferentially associates with IRD-prone regions. The winged helix domain, unique to eIF2D but absent in MCTS1–DENR, enhances its binding to 40S subunits, but likely clashes with ABCE1 during stop-codon-associated recycling. Loss of eIF2D reduces the expression of IRD-inducing proteins, including splicing factors. Together, these findings define a previously unappreciated role for eIF2D in 40S recycling and clarify its mechanistic divergence from the MCTS1–DENR complex. en-copyright= kn-copyright= en-aut-name=IchiharaKazuya en-aut-sei=Ichihara en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShiraishiTaichi en-aut-sei=Shiraishi en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChadaniYuhei en-aut-sei=Chadani en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitoYuki en-aut-sei=Kito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShiraishiChisa en-aut-sei=Shiraishi en-aut-mei=Chisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirataMina en-aut-sei=Hirata en-aut-mei=Mina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiYuta en-aut-sei=Takahashi en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoboAkinao en-aut-sei=Kobo en-aut-mei=Akinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HatanoAtsushi en-aut-sei=Hatano en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsumotoMasaki en-aut-sei=Matsumoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MachidaKodai en-aut-sei=Machida en-aut-mei=Kodai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ImatakaHiroaki en-aut-sei=Imataka en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ToyodaAtsushi en-aut-sei=Toyoda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Mishiro-SatoEmi en-aut-sei=Mishiro-Sato en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NojimaTakayuki en-aut-sei=Nojima en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ItoTakuhiro en-aut-sei=Ito en-aut-mei=Takuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TaguchiHideki en-aut-sei=Taguchi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakayamaKeiichi I en-aut-sei=Nakayama en-aut-mei=Keiichi I kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MatsumotoAkinobu en-aut-sei=Matsumoto en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=2 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=3 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Division of Cell Biology, Medical Institute of Bioregulation, Kyushu University kn-affil= affil-num=5 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=6 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=7 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=8 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=9 en-affil=Department of Omics and Systems Biology, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=10 en-affil=Department of Omics and Systems Biology, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=11 en-affil=Graduate School of Engineering, University of Hyogo kn-affil= affil-num=12 en-affil=Graduate School of Engineering, University of Hyogo kn-affil= affil-num=13 en-affil=Advanced Genomics Center, National Institute of Genetics kn-affil= affil-num=14 en-affil=Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University kn-affil= affil-num=15 en-affil=Medical Institute of Bioregulation, Kyushu University kn-affil= affil-num=16 en-affil=Laboratory for Translation Structural Biology, RIKEN Center for Integrative Medical Sciences kn-affil= affil-num=17 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=18 en-affil=Division of Cell Biology, Medical Institute of Bioregulation, Kyushu University kn-affil= affil-num=19 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=1 article-no= start-page=1720 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A genome-wide association study identifies the GPM6A locus associated with age at onset in ALS en-subtitle= kn-subtitle= en-abstract= kn-abstract=Amyotrophic lateral sclerosis (ALS) exhibits considerable clinical variability, such as differences in age at onset (AAO). Multiple factors, including genetic factors, may underlie this variability; however, the specific determinants remain unclear. To identify genes affecting AAO, we have conducted a genome-wide association study in Japanese patients with ALS (discovery cohort: n = 1808; replication cohort: n = 207). Here, we show that the minor A allele of rs113161727 at the ADAM29-GPM6A locus is associated with a younger AAO in the discovery cohort (effect, -4.27 years; p = 4.60 × 10-8); this finding has been confirmed in the replication cohort (p = 0.0068) and meta-analysis (p = 1.08 × 10−9). Among 65 ALS patients with a SOD1 mutation, the AAO has been found to be 10.2 years younger in those with the A allele than in those without it (p = 0.002). This variant correlates with GPM6A upregulation in iPSC-derived motor neurons, suggesting GPM6A as a candidate AAO modifier. Overall, our study highlights the impact of genetic modifiers on ALS heterogeneity and provides a potential target for delaying disease onset. en-copyright= kn-copyright= en-aut-name=NakamuraRyoichi en-aut-sei=Nakamura en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TohnaiGenki en-aut-sei=Tohnai en-aut-mei=Genki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AtsutaNaoki en-aut-sei=Atsuta en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsudaYumi en-aut-sei=Matsuda en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MorimotoSatoru en-aut-sei=Morimoto en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoDaisuke en-aut-sei=Ito en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatsunoMasahisa en-aut-sei=Katsuno en-aut-mei=Masahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IzumiYuishin en-aut-sei=Izumi en-aut-mei=Yuishin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoritaMitsuya en-aut-sei=Morita en-aut-mei=Mitsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IwataIkuko en-aut-sei=Iwata en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YabeIchiro en-aut-sei=Yabe en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakazatoTomoko en-aut-sei=Nakazato en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HattoriNobutaka en-aut-sei=Hattori en-aut-mei=Nobutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HirayamaTakehisa en-aut-sei=Hirayama en-aut-mei=Takehisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KanoOsamu en-aut-sei=Kano en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TamuraAsako en-aut-sei=Tamura en-aut-mei=Asako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SuzukiNaoki en-aut-sei=Suzuki en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=AokiMasashi en-aut-sei=Aoki en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShibuyaKazumoto en-aut-sei=Shibuya en-aut-mei=Kazumoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KuwabaraSatoshi en-aut-sei=Kuwabara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=OdaMasaya en-aut-sei=Oda en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HashimotoRina en-aut-sei=Hashimoto en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=AibaIkuko en-aut-sei=Aiba en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=IshiharaTomohiko en-aut-sei=Ishihara en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=OnoderaOsamu en-aut-sei=Onodera en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=BokudaKota en-aut-sei=Bokuda en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=ShimizuToshio en-aut-sei=Shimizu en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=IkedaYoshio en-aut-sei=Ikeda en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=HasegawaKazuko en-aut-sei=Hasegawa en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=TanakaFumiaki en-aut-sei=Tanaka en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=YokotaTakanori en-aut-sei=Yokota en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=KanaiKazuaki en-aut-sei=Kanai en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=NotoYu-ichi en-aut-sei=Noto en-aut-mei=Yu-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=KajiRyuji en-aut-sei=Kaji en-aut-mei=Ryuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=WatanabeHirohisa en-aut-sei=Watanabe en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=KonishiTomoko en-aut-sei=Konishi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=HasegawaMikiko en-aut-sei=Hasegawa en-aut-mei=Mikiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=FukayaHozuki en-aut-sei=Fukaya en-aut-mei=Hozuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=NiwaJun-ichi en-aut-sei=Niwa en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=DoyuManabu en-aut-sei=Doyu en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=OkadaYohei en-aut-sei=Okada en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=NakamuraShiho en-aut-sei=Nakamura en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=OzawaFumiko en-aut-sei=Ozawa en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=OkanoHideyuki en-aut-sei=Okano en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=NakatochiMasahiro en-aut-sei=Nakatochi en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=SobueGen en-aut-sei=Sobue en-aut-mei=Gen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= affil-num=1 en-affil=Department of Neurology, Aichi Medical University School of Medicine kn-affil= affil-num=2 en-affil=Division of ALS Research, Aichi Medical University School of Medicine kn-affil= affil-num=3 en-affil=Department of Neurology, Aichi Medical University School of Medicine kn-affil= affil-num=4 en-affil=Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Keio University Regenerative Medicine Research Center, Kawasaki kn-affil= affil-num=6 en-affil=Department of Neurology, Nagoya University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Neurology, Nagoya University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Neurology, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=9 en-affil=Division of Neurology, Department of Internal Medicine, Jichi Medical University kn-affil= affil-num=10 en-affil=Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=11 en-affil=Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=12 en-affil=Department of Neurology, Juntendo University School of Medicine kn-affil= affil-num=13 en-affil=Department of Neurology, Juntendo University School of Medicine kn-affil= affil-num=14 en-affil=Department of Neurology, Toho University Faculty of Medicine kn-affil= affil-num=15 en-affil=Department of Neurology, Toho University Faculty of Medicine kn-affil= affil-num=16 en-affil=Department of Neurology, Mie University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Department of Neurology, Tohoku University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Neurology, Tohoku University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=20 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=21 en-affil=Department of Neurology, Vihara Hananosato Hospital kn-affil= affil-num=22 en-affil=Department of Neurology, NHO Higashinagoya National Hospital kn-affil= affil-num=23 en-affil=Department of Neurology, NHO Higashinagoya National Hospital kn-affil= affil-num=24 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=25 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=26 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=27 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=28 en-affil=Department of Neurology, Tokyo Metropolitan Neurological Hospital kn-affil= affil-num=29 en-affil=Department of Neurology, Tokyo Metropolitan Neurological Hospital kn-affil= affil-num=30 en-affil=Department of Neurology, Gunma University Graduate School of Medicine kn-affil= affil-num=31 en-affil=Division of Neurology, NHO Sagamihara National Hospital kn-affil= affil-num=32 en-affil=Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine kn-affil= affil-num=33 en-affil=Department of Neurology and Neurological Science, NucleoTIDE and PepTIDE Drug Discovery Center (TIDE), Institute of Science Tokyo kn-affil= affil-num=34 en-affil=Department of Neurology, Fukushima Medical University School of Medicine kn-affil= affil-num=35 en-affil=Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=36 en-affil=Department of Neurology, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=37 en-affil=Department of Neurology, Fujita Health University kn-affil= affil-num=38 en-affil=Division of ALS Research, Aichi Medical University School of Medicine kn-affil= affil-num=39 en-affil=Division of ALS Research, Aichi Medical University School of Medicine kn-affil= affil-num=40 en-affil=Division of ALS Research, Aichi Medical University School of Medicine kn-affil= affil-num=41 en-affil=Department of Neurology, Aichi Medical University School of Medicine kn-affil= affil-num=42 en-affil=Department of Neurology, Aichi Medical University School of Medicine kn-affil= affil-num=43 en-affil=Department of Neurology, Aichi Medical University School of Medicine kn-affil= affil-num=44 en-affil=Keio University Regenerative Medicine Research Center, Kawasaki kn-affil= affil-num=45 en-affil=Keio University Regenerative Medicine Research Center, Kawasaki kn-affil= affil-num=46 en-affil=Keio University Regenerative Medicine Research Center, Kawasaki kn-affil= affil-num=47 en-affil=Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine kn-affil= affil-num=48 en-affil=Division of ALS Research, Aichi Medical University School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=445 cd-vols= no-issue= article-no= start-page=134071 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cardiac characteristics of Fabry disease from baseline enrolment data in a nationwide prospective Japanese registry en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Fabry disease (FD) is an important disease in the cardiovascular field because a significant proportion of patients with FD die from cardiac lesions.
Methods: A multicenter prospective registration study of patients with FD throughout Japan was designed. The baseline clinical characteristics of 175 patients are presented here.
Results: The mean ages at enrolment and at diagnosis were 52 ± 16 and 43 ± 18 years, respectively, with men accounting for 38 % of the patients. In the cohort, 24 % of the patients had the classical hemizygote male type, whereas 14 % had the late-onset male type, and 62 % had the heterozygote female type. On electrocardiography data at enrolment in 92 patients with left ventricular hypertrophy (LVH) (maximum LV wall thickness > 12 mm), 12 % showed a short PQ interval (< 120 msec), and 33 % had a short PendQ interval (≤ 40 msec). The Sokolow-Lyon voltage was high (6.1 ± 13.1 mv). Regarding the distribution of LVH patterns, 77 % of the patients showed concentric diffuse LVH, 16 % of the patients had asymmetric septal hypertrophy, and 1 % of the patients had hypertrophy confined to the LV apex. With regard to implantation of cardiac devices, permanent pacemakers had been implanted in 5 % of the patients and defibrillators had been implanted in 12 patients (7 %), for primary prevention in nine patients and for secondary prevention in three patients.
Conclusion: As the first large-scale prospective registry of FD patients in Japan, this study has provided valuable baseline data for the cardiac features and management of FD. en-copyright= kn-copyright= en-aut-name=KuboToru en-aut-sei=Kubo en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaekawaYuichiro en-aut-sei=Maekawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HongoKenichi en-aut-sei=Hongo en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoSaori en-aut-sei=Yamamoto en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IzumiyaYasuhiro en-aut-sei=Izumiya en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamakawaHiroyuki en-aut-sei=Yamakawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YanoToshiyuki en-aut-sei=Yano en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiguchiKoji en-aut-sei=Higuchi en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuramotoYuki en-aut-sei=Kuramoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakagawaNaoki en-aut-sei=Nakagawa en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AmanoMasashi en-aut-sei=Amano en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamadaYu en-aut-sei=Yamada en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OikawaMasayoshi en-aut-sei=Oikawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IidaYuichiro en-aut-sei=Iida en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TsujitaKenichi en-aut-sei=Tsujita en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MatsueYuya en-aut-sei=Matsue en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=IzawaHideo en-aut-sei=Izawa en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SuzukiAtsushi en-aut-sei=Suzuki en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=NagatomoYuji en-aut-sei=Nagatomo en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=NagaiToshiyuki en-aut-sei=Nagai en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KidaKeisuke en-aut-sei=Kida en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=NakamuraKazuto en-aut-sei=Nakamura en-aut-mei=Kazuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=IkenagaHiroki en-aut-sei=Ikenaga en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KandaTakahiro en-aut-sei=Kanda en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KinugasaYoshiharu en-aut-sei=Kinugasa en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ItoHiromasa en-aut-sei=Ito en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=OnoueKenji en-aut-sei=Onoue en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KanamoriHiromitsu en-aut-sei=Kanamori en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=KitaokaHiroaki en-aut-sei=Kitaoka en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University kn-affil= affil-num=2 en-affil=Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine kn-affil= affil-num=3 en-affil=Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Osaka Metropolitan University, Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, The University of Osaka Graduate School of Medicine kn-affil= affil-num=10 en-affil=Division of Cardiology and Nephrology, Department of Internal Medicine, Asahikawa Medical University kn-affil= affil-num=11 en-affil=Department of Heart Failure and Transplantation, National Cerebral and Cardiovascular Center kn-affil= affil-num=12 en-affil=Department of Cardiology, Institute of Medicine, University of Tsukuba kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, Fukushima Medical University kn-affil= affil-num=14 en-affil=Department of Cardiovascular Medicine, Kitasato University School of Medicine kn-affil= affil-num=15 en-affil=Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University kn-affil= affil-num=16 en-affil=Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Department of Cardiology, Fujita Health University kn-affil= affil-num=18 en-affil=Department of Cardiology, Tokyo Women's Medical University kn-affil= affil-num=19 en-affil=Department of Cardiology, National Defense Medical College kn-affil= affil-num=20 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=21 en-affil=Department of Pharmacology, St. Marianna University School of Medicine kn-affil= affil-num=22 en-affil=Department of Cardiovascular Medicine, University of Yamanashi, Faculty of Medicine kn-affil= affil-num=23 en-affil=Center for Advanced Heart Failure, Okayama University Hospital kn-affil= affil-num=24 en-affil=Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences kn-affil= affil-num=25 en-affil=Department of Internal Medicine, Division of Cardiology, Hamamatsu Red Cross Hospital kn-affil= affil-num=26 en-affil=Department of Cardiovascular Medicine and Endocrinology and Metabolism, Faculty of Medicine, Tottori University kn-affil= affil-num=27 en-affil=Department of Cardiology, Mie University Hospital kn-affil= affil-num=28 en-affil=Department of Cardiovascular Medicine, Nara Medical University kn-affil= affil-num=29 en-affil=Department of Cardiology, Gifu University Graduate School of Medicine kn-affil= affil-num=30 en-affil=Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University kn-affil= en-keyword=Fabry disease kn-keyword=Fabry disease en-keyword=Prospective study kn-keyword=Prospective study en-keyword=Left ventricular hypertrophy kn-keyword=Left ventricular hypertrophy en-keyword=Treatment kn-keyword=Treatment END start-ver=1.4 cd-journal=joma no-vol=992 cd-vols= no-issue=1 article-no= start-page=27 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251003 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Observing Supernova Neutrino Light Curves with Super-Kamiokande. VI. A Practical Data Analysis Technique Considering Realistic Experimental Backgrounds en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neutrinos from supernovae, especially those emitted during the late phase of core collapse, are essential for understanding the final stages of massive star evolution. We have been dedicated to developing methods for the analysis of neutrinos emitted during the late phase and observed at Super-Kamiokande (SK). Our previous studies have successfully demonstrated the potential of various analysis methods in extracting essential physical properties; however, the lack of background consideration has limited their practical application. In this study, we address this issue by incorporating a realistic treatment of the experimental signal and background events with the on-going SK experiment. We therefore optimize our analysis framework to reflect realistic observational conditions, including both signal and background events. Using this framework we study several long-time supernova models, simulating the late phase neutrino observation in SK and focusing in particular on the identification of the last observed event. We discuss the possibility of model discrimination methods using timing information from this last observed event. en-copyright= kn-copyright= en-aut-name=NakanishiFumi en-aut-sei=Nakanishi en-aut-mei=Fumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakazatoKen’ichiro en-aut-sei=Nakazato en-aut-mei=Ken’ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaMasayuki en-aut-sei=Harada en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KoshioYusuke en-aut-sei=Koshio en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkahoRyuichiro en-aut-sei=Akaho en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AshidaYosuke en-aut-sei=Ashida en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaradaAkira en-aut-sei=Harada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MoriMasamitsu en-aut-sei=Mori en-aut-mei=Masamitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SumiyoshiKohsuke en-aut-sei=Sumiyoshi en-aut-mei=Kohsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SuwaYudai en-aut-sei=Suwa en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WendellRoger A. en-aut-sei=Wendell en-aut-mei=Roger A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ZaizenMasamichi en-aut-sei=Zaizen en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Physics, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Arts and Science, Kyushu University kn-affil= affil-num=3 en-affil=Kamioka Observatory, Institute for Cosmic Ray Research, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Physics, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Science and Engineering, Waseda University kn-affil= affil-num=6 en-affil=Department of Physics, Tohoku University kn-affil= affil-num=7 en-affil=National Institute of Technology, Ibaraki College kn-affil= affil-num=8 en-affil=Division of Science, National Astronomical Observatory of Japan kn-affil= affil-num=9 en-affil=National Institute of Technology, Numazu College kn-affil= affil-num=10 en-affil=Department of Earth Science and Astronomy, The University of Tokyo kn-affil= affil-num=11 en-affil=Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU, WPI), Todai Institutes for Advanced Study, The University of Tokyo kn-affil= affil-num=12 en-affil=Department of Earth Science and Astronomy, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=260 cd-vols= no-issue= article-no= start-page=115195 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An entangled material made from fiber aerosol deposition method en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study demonstrates the successful application of Aerosol Deposition (AD) technology to short carbon fibers (length < 1 mm), enabling the rapid, three-dimensional (3D) fabrication of objects with vertical growth rates up to 0.3 mm/s, a significant improvement over conventional additive manufacturing. Through a series of experiments using this novel Fiber Aerosol Deposition (FAD) technology, three fiber lengths (47, 85, and 111 μm) and four substrate materials (carbon, polypropylene, polyethylene, and acrylonitrile butadiene styrene (ABS)) were investigated. Our findings indicate that both carbon substrate entanglement and fiber length critically influence deposition efficiency. Scanning electron microscopy (SEM) and X-ray computed tomography (CT) analyses reveal that during formation, longer fibers (>100 μm) initially create a cage-like framework, which is subsequently filled by shorter fibers. Density measurements and fiber distribution analysis confirmed that structures predominantly composed of shorter fibers exhibit higher packing densities, consistent with their role as filler material. These results collectively suggest that the FAD method’s formation mechanism relies on frictional entanglement rather than the room-temperature impact consolidation (RTIC) effect characteristic of traditional AD. This breakthrough presents a promising new technique for forming short fibers into functional 3D architectures, with potential applications extending to proteins, polymer fibers, and biomaterial fibers. en-copyright= kn-copyright= en-aut-name=YuHongwu en-aut-sei=Yu en-aut-mei=Hongwu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaNaoshi en-aut-sei=Ikeda en-aut-mei=Naoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriMasakazu en-aut-sei=Mori en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanoJun en-aut-sei=Kano en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ParkJae-Hyuk en-aut-sei=Park en-aut-mei=Jae-Hyuk kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkedoJun en-aut-sei=Akedo en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, University of Okayama kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, University of Okayama kn-affil= affil-num=3 en-affil=Ryukoku University kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, University of Okayama kn-affil= affil-num=5 en-affil=School of Advanced Materials Science & Engineering, Sungkyunkwan University kn-affil= affil-num=6 en-affil=National Institute of Advanced Industrial Science and Technology kn-affil= en-keyword=Aerosol deposition kn-keyword=Aerosol deposition en-keyword=Thick film kn-keyword=Thick film en-keyword=Room temperature kn-keyword=Room temperature en-keyword=Ceramic coating kn-keyword=Ceramic coating en-keyword=RTIC kn-keyword=RTIC en-keyword=Carbon fiber kn-keyword=Carbon fiber END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=6 article-no= start-page=3541 end-page=3552 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250311 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Metal-Cation Doping on Photocatalytic H2 Evolution Activity of Layered Perovskite Oxynitride K2LaTa2O6N en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aliovalent cation doping into a heterogeneous photocatalyst affects several of its physicochemical properties, including its morphological characteristics, optical absorption behavior, and charge carrier dynamics, causing a drastic change in its photocatalytic activity. In the present work, we investigated the effects of aliovalent cation doping on the visible-light H2-evolution photocatalytic activity of the Ruddlesden–Popper layered perovskite oxynitride K2LaTa2O6N. The photocatalytic activity toward H2 evolution from an aqueous NaI solution was found to be enhanced by an increase in the specific surface area of the K2LaTa2O6N photocatalyst, which could be realized upon doping with lower-valence cations (e.g., Mg2+, Al3+, and Ga3+). Among the dopants examined at 1 mol % doping, Ga resulted in the highest activity. The activity of the Ga-doped specimen was further improved with increasing Ga concentration, where the maximal activity was obtained at 10 mol %, corresponding to an apparent quantum yield of 2.7 ± 0.4% at 420 nm from aqueous methanol. This number is the highest reported for a layered oxynitride photocatalyst. In the Ga-doped K2LaTa2O6N, a trade-off was observed between the Ga concentration and the photocatalytic activity. Although doping with Ga reduced the particle size of K2LaTa2O6N and suppressed undesirable charge recombination, it led to an enlarged bandgap, unsuitable for visible-light absorption. en-copyright= kn-copyright= en-aut-name=TsuchikadoHideya en-aut-sei=Tsuchikado en-aut-mei=Hideya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AnabukiShuji en-aut-sei=Anabuki en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=CretuOvidiu en-aut-sei=Cretu en-aut-mei=Ovidiu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KinoshitaYuki en-aut-sei=Kinoshita en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HattoriMasashi en-aut-sei=Hattori en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShiromaYuta en-aut-sei=Shiroma en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FanDongxiao en-aut-sei=Fan en-aut-mei=Dongxiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkazakiMegumi en-aut-sei=Okazaki en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SomaTakuto en-aut-sei=Soma en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiwariFumitaka en-aut-sei=Ishiwari en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NozawaShunsuke en-aut-sei=Nozawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YokoiToshiyuki en-aut-sei=Yokoi en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HaraMichikazu en-aut-sei=Hara en-aut-mei=Michikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KimotoKoji en-aut-sei=Kimoto en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamakataAkira en-aut-sei=Yamakata en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SaekiAkinori en-aut-sei=Saeki en-aut-mei=Akinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MaedaKazuhiko en-aut-sei=Maeda en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Chemistry, School of Science, Institute of Science Tokyo kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Electron Microscopy Group, National Institute for Materials Science (NIMS) kn-affil= affil-num=4 en-affil=Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=Institute of Integrated Research, Institute of Science Tokyo kn-affil= affil-num=6 en-affil=Department of Chemistry, School of Science, Institute of Science Tokyo kn-affil= affil-num=7 en-affil=Institute of Materials Structure Science High Energy Accelerator Research Organization kn-affil= affil-num=8 en-affil=Department of Chemistry, School of Science, Institute of Science Tokyo kn-affil= affil-num=9 en-affil=Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Institute of Science Tokyo kn-affil= affil-num=10 en-affil=Department of Applied Chemistry, Graduate School of Engineering, Osaka University kn-affil= affil-num=11 en-affil=Institute of Materials Structure Science High Energy Accelerator Research Organization kn-affil= affil-num=12 en-affil=Institute of Integrated Research, Institute of Science Tokyo kn-affil= affil-num=13 en-affil=Institute of Integrated Research, Institute of Science Tokyo kn-affil= affil-num=14 en-affil=Electron Microscopy Group, National Institute for Materials Science (NIMS) kn-affil= affil-num=15 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=16 en-affil=Department of Applied Chemistry, Graduate School of Engineering, Osaka University kn-affil= affil-num=17 en-affil=Department of Chemistry, School of Science, Institute of Science Tokyo kn-affil= en-keyword=artificial photosynthesis kn-keyword=artificial photosynthesis en-keyword=heterogeneous photocatalysis kn-keyword=heterogeneous photocatalysis en-keyword=mixed-anion compounds kn-keyword=mixed-anion compounds en-keyword=topochemical reaction kn-keyword=topochemical reaction en-keyword=visible light kn-keyword=visible light END start-ver=1.4 cd-journal=joma no-vol=187 cd-vols= no-issue= article-no= start-page=106403 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nitrogen distribution and nitrogen isotope fractionation in synthetic 2:1 phyllosilicates under hydrothermal conditions at 200 °C and saturated vapor pressure en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigates nitrogen distribution and isotope fractionation within synthetic 2:1 phyllosilicates, simulating submarine hydrothermal environments at 200 °C and saturated vapor pressure. XRD and EDS results revealed the potential coexistence of multiple cations in the interlayer of synthetic 2:1 phyllosilicate, concurrently suggesting cation substitution in the tetrahedral and/or octahedral sheets. Meanwhile, the iron-enriched 25-5 sample exhibited restricted interlayer expansibility. NH4+ absorptions were identified in the NH4-stretching (3200–2800 cm−1) and NH4-bending (1450–1400 cm−1) regions, with wavenumber shifts indicating the influence of interlayer water removal. At pH 10.56, over 95% of nitrogen was released into the gas phase, while at pH 8.88, nitrogen proportions in the liquid and gas phases were comparable (average 48–49%). Experiments with iron at pH ∼8.80 showed that the nitrogen proportion in the gas phase (average 28%) was more than twofold lower than that in the liquid phase (average 68%). Equilibrium isotope fractionation factors indicated discernible preference for heavier nitrogen isotopes in the solid phase (αsolid-liquid = 1.009–1.021 and αsolid-gas = 1.011–1.027). The αliquid-gas range for sample 25–2 was 1.001–1.008, while that for the iron-enriched composite 25–5 was 0.997–1.010. Our experimental studies have confirmed that, in the absence of exchange interactions with external substances possessing different nitrogen isotope ratios, nitrogen isotope fractionation between ammonium and ammonia, controlled by variations in temperature and pH during mineralization, plays a crucial role in the variation of nitrogen isotope ratios. Additionally, we confirmed that metal-amines influence nitrogen isotope fractionation by modulating ammonia gas emission. These findings enhance our understanding of nitrogen cycling across the gas, liquid, and solid phases in submarine hydrothermal systems. en-copyright= kn-copyright= en-aut-name=JoJaeguk en-aut-sei=Jo en-aut-mei=Jaeguk kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamanakaToshiro en-aut-sei=Yamanaka en-aut-mei=Toshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyoshiYouko en-aut-sei=Miyoshi en-aut-mei=Youko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiMasaya en-aut-sei=Suzuki en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KuwaharaYoshihiro en-aut-sei=Kuwahara en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KadotaIsao en-aut-sei=Kadota en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ChibaHitoshi en-aut-sei=Chiba en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LeeBum Han en-aut-sei=Lee en-aut-mei=Bum Han kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Geo-Resources and Environment, Geological Survey of Japan, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=4 en-affil=Research Institute for Geo-Resources and Environment, Geological Survey of Japan, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=5 en-affil=Department of Environmental Changes, Faculty of Social and Cultural Studies, Kyushu University kn-affil= affil-num=6 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Critical Minerals Research Center, Korea Institute of Geoscience & Mineral Resources (KIGAM) kn-affil= en-keyword=Synthetic 2:1 phyllosilicates kn-keyword=Synthetic 2:1 phyllosilicates en-keyword=Nitrogen distribution kn-keyword=Nitrogen distribution en-keyword=Nitrogen isotope fractionation kn-keyword=Nitrogen isotope fractionation en-keyword=Hydrothermal system kn-keyword=Hydrothermal system END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=6 article-no= start-page=dsaf030 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=MedakaBase as a unified genomic resource platform for medaka fish biology en-subtitle= kn-subtitle= en-abstract= kn-abstract=Medaka, a group of small, mostly freshwater fishes in the teleost order Beloniformes, includes the rice fish Oryzias latipes, a useful model organism studied in diverse biological fields. Chromosome-scale genome sequences of the Hd-rR strain of this species were obtained in 2007, and its improved version has facilitated various genome-wide studies. However, despite its widespread utility, omics data for O. latipes are dispersed across various public databases and lack a unified platform. To address this, the medaka section of the National Bioresource Project (NBRP) of Japan established a genome informatics team in 2022 tasked with providing various in silico solutions for bench biologists. This initiative led to the launch of MedakaBase (https://medakabase.nbrp.jp), a web server that enables gene-oriented analysis including exhaustive sequence similarity searches. MedakaBase also provides on-demand browsing of diverse genome-wide datasets, including tissue-specific transcriptomes and intraspecific genomic variations, integrated with gene models from different sources. Additionally, the platform offers gene models optimized for single-cell transcriptome analysis, which often requires coverage of the 3′ untranslated region (UTR) of transcripts. Currently, MedakaBase provides genome-wide data for seven Oryzias species, including original data for O. mekongensis and O. luzonensis produced by the NBRP team. This article outlines technical details behind the data provided by MedakaBase. en-copyright= kn-copyright= en-aut-name=MorikamiKenji en-aut-sei=Morikami en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanizawaYasuhiro en-aut-sei=Tanizawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YaguraMasaru en-aut-sei=Yagura en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoMika en-aut-sei=Sakamoto en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawamotoShoko en-aut-sei=Kawamoto en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraYasukazu en-aut-sei=Nakamura en-aut-mei=Yasukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamaguchiKatsushi en-aut-sei=Yamaguchi en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShigenobuShuji en-aut-sei=Shigenobu en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NaruseKiyoshi en-aut-sei=Naruse en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AnsaiSatoshi en-aut-sei=Ansai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KurakuShigehiro en-aut-sei=Kuraku en-aut-mei=Shigehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems kn-affil= affil-num=2 en-affil=Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems kn-affil= affil-num=3 en-affil=Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems kn-affil= affil-num=4 en-affil=Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems kn-affil= affil-num=5 en-affil=Department of Genetics, Sokendai (Graduate University for Advanced Studies) kn-affil= affil-num=6 en-affil=Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems kn-affil= affil-num=7 en-affil=Trans-Omics Facility, National Institute for Basic Biology kn-affil= affil-num=8 en-affil=Trans-Omics Facility, National Institute for Basic Biology kn-affil= affil-num=9 en-affil=Laboratory of Bioresources, National Institute for Basic Biology, National Institutes of Natural Sciences kn-affil= affil-num=10 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=11 en-affil=Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems kn-affil= en-keyword=medaka kn-keyword=medaka en-keyword=comparative genomics kn-keyword=comparative genomics en-keyword=genome browser kn-keyword=genome browser en-keyword=MedakaBase kn-keyword=MedakaBase en-keyword=Beloniformes kn-keyword=Beloniformes END start-ver=1.4 cd-journal=joma no-vol=55 cd-vols= no-issue=5 article-no= start-page=547 end-page=555 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250223 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multicenter, open-label, randomized, controlled study to test the utility of electronic patient-reported outcome monitoring in patients with unresectable advanced cancers or metastatic/recurrent solid tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Electronic patient-reported outcome (ePRO) monitoring for patients undergoing cancer chemotherapy may provide qualified and early detection of adverse events or disease-related symptoms, leading to improved patient care. The aim of this study is to examine whether addition of ePRO monitoring to routine medical care contributes to improved overall survival and quality of life of cancer patients undergoing chemotherapy. Patients with unresectable advanced cancers or metastatic/recurrent solid tumors receiving systemic chemotherapy will be randomized to an ePRO monitoring group and a usual care group. The ePRO group will conduct weekly symptom monitoring using an electronic device after study enrollment until the end of the study. Monitoring results will be returned to medical personnel and used as information for patient care. The primary endpoints are overall survival and health related quality of life. The initial target sample size for the study was 1500 patients. However, due to delays in enrollment, the target was readjusted to 500 patients. Enrollment has been completed, and the study is now in the follow-up phase. en-copyright= kn-copyright= en-aut-name=TairaNaruto en-aut-sei=Taira en-aut-mei=Naruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KiyotaNaomi en-aut-sei=Kiyota en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikawaYuichiro en-aut-sei=Kikawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoKyoko en-aut-sei=Kato en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KubotaKaoru en-aut-sei=Kubota en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TateishiRyosuke en-aut-sei=Tateishi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakataAkinobu en-aut-sei=Nakata en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaritaYukiya en-aut-sei=Narita en-aut-mei=Yukiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IwataHiroji en-aut-sei=Iwata en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=GemmaAkihiko en-aut-sei=Gemma en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShimozumaKojiro en-aut-sei=Shimozuma en-aut-mei=Kojiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MuroKei en-aut-sei=Muro en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IwamotoTetsuya en-aut-sei=Iwamoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakumotoYuki en-aut-sei=Takumoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ShiroiwaTakeru en-aut-sei=Shiroiwa en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FukudaTakashi en-aut-sei=Fukuda en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YamaguchiTakuhiro en-aut-sei=Yamaguchi en-aut-mei=Takuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HagiwaraYasuhiro en-aut-sei=Hagiwara en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MinamiHironobu en-aut-sei=Minami en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School kn-affil= affil-num=2 en-affil=Department of Medical Oncology and Hematology, Cancer Center, Kobe University Hospital kn-affil= affil-num=3 en-affil=Department of Breast Surgery, Kansai Medical University kn-affil= affil-num=4 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Medical Oncology, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=6 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Advanced Clinical Research and Development, Nagoya City University kn-affil= affil-num=13 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=14 en-affil=Department of Biomed Sciences, College of Life Sciences, Ritsumeikan University kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health kn-affil= affil-num=17 en-affil=Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health kn-affil= affil-num=18 en-affil=Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health kn-affil= affil-num=19 en-affil=Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health kn-affil= affil-num=20 en-affil=Division of Biostatistics, Tohoku University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Biostatistics, Division of Health Sciences and Nursing, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=22 en-affil=Division of Medical Oncology and Hematology, Department of Medicine, Kobe University Graduate School of Medicine kn-affil= en-keyword=electronic patient-reported outcomes monitoring kn-keyword=electronic patient-reported outcomes monitoring en-keyword=advanced cancers kn-keyword=advanced cancers en-keyword=systemic chemotherapy kn-keyword=systemic chemotherapy en-keyword=randomized controlled study kn-keyword=randomized controlled study en-keyword=quality of life kn-keyword=quality of life en-keyword=overall survival kn-keyword=overall survival END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=1 article-no= start-page=e70144 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250616 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Japanese Multi‐Institution Study of Success Rates of Wire‐Guided Biliary Cannulation During Endoscopic Retrograde Cholangiopancreatography in Relation to Guidewire tip Length (JMIT Study) (With Video) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Wire-guided cannulation (WGC) reportedly increases the successful biliary cannulation rate and reduces the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis. Currently, various types of guidewires are available. However, the effect of the length of flexible-tip guidewires on the success rate of biliary cannulation under WGC and the rate of adverse events, especially post-endoscopic retrograde cholangiopancreatography pancreatitis, is unclear. The aim of this study was to compare the influence of long-tapered and short-tapered tips of a 0.025-inch guidewire on outcomes in primary selective biliary cannulation.
Methods: Consecutive patients who underwent biliary access under endoscopic retrograde cholangiopancreatography guidance using WGC at 27 high-volume centers in Japan were enrolled in this prospective registration study. The primary outcome was the technical success rate of biliary cannulation. The secondary outcomes were the rates of adverse events, biliary cannulation time, and number of guidewire insertions into the pancreatic duct.
Results: A total of 530 patients underwent biliary cannulation for biliary disease with native papilla between April 2021 and December 2023. The technical success rate of biliary cannulation was 86.1% (161/187) in the long-tip group and 84.3% (289/343) in the short-tip group, indicating no significant differences between the two groups. Although the frequency of post-endoscopic retrograde cholangiopancreatography was not significantly different, the successful biliary cannulation rate without guidewire mis-insertion into the main pancreatic duct was significantly higher in the long tip group (64.7%, 121/187) compared with the short tip group (54.2%, 186/343p = 0.02).
Conclusions: In conclusion, WGC using long-tip guidewires might reduce the risk of guidewire insertion into the main pancreatic duct. en-copyright= kn-copyright= en-aut-name=OguraTakeshi en-aut-sei=Ogura en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanisakaYuki en-aut-sei=Tanisaka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SekineMasanari en-aut-sei=Sekine en-aut-mei=Masanari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiKatsumasa en-aut-sei=Kobayashi en-aut-mei=Katsumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaruyamaHirotsugu en-aut-sei=Maruyama en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HiraiShinji en-aut-sei=Hirai en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShiomiHideyuki en-aut-sei=Shiomi en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShigekawaMinoru en-aut-sei=Shigekawa en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuwataniMasaki en-aut-sei=Kuwatani en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IkezawaKenji en-aut-sei=Ikezawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ItonagaMasahiro en-aut-sei=Itonaga en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakenakaMamoru en-aut-sei=Takenaka en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HijiokaSusumu en-aut-sei=Hijioka en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IkeuraTsukasa en-aut-sei=Ikeura en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=DoiShinpei en-aut-sei=Doi en-aut-mei=Shinpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujimoriNao en-aut-sei=Fujimori en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KoizumiKazuya en-aut-sei=Koizumi en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakaiYousuke en-aut-sei=Nakai en-aut-mei=Yousuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=InoueTadahisa en-aut-sei=Inoue en-aut-mei=Tadahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MukaiShuntaro en-aut-sei=Mukai en-aut-mei=Shuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MinamiRyuki en-aut-sei=Minami en-aut-mei=Ryuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MandaiKoichiro en-aut-sei=Mandai en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MatsudaAtsuhiro en-aut-sei=Matsuda en-aut-mei=Atsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=IwashitaTakuji en-aut-sei=Iwashita en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KawashimaHiroki en-aut-sei=Kawashima en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ItoiTakao en-aut-sei=Itoi en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= affil-num=1 en-affil=Endoscopy Center, Osaka Medical and Pharmaceutical University kn-affil= affil-num=2 en-affil=Gastroenterology, Saitama Medical University International Medical Center kn-affil= affil-num=3 en-affil=Department of Gastroenterology Jichi Medical University, Saitama Medical Center kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Tokyo Metropolitan Bokutoh Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=6 en-affil=Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Division of Hepatobiliary and Pancreatic Diseases, Hyogo Medical University kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Hokkaido University Hospital kn-affil= affil-num=10 en-affil=Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute kn-affil= affil-num=11 en-affil=Second Department of Internal Medicine, Wakayama Medical University kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University kn-affil= affil-num=13 en-affil=Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital kn-affil= affil-num=14 en-affil=Third Department of Internal Medicine, Kansai Medical University kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Teikyo University Mizonokuchi Hospital kn-affil= affil-num=16 en-affil=Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=17 en-affil=Department of Gastroenterology, Medicine Center, Shonan Kamakura General Hospital kn-affil= affil-num=18 en-affil=Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=19 en-affil=Department of Gastroenterology, Aichi Medical University kn-affil= affil-num=20 en-affil=Department of Gastroenterology and Hepatology, Tokyo Medical University kn-affil= affil-num=21 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=22 en-affil=Department of Gastroenterology, Tenri Hospital kn-affil= affil-num=23 en-affil=Department of Gastroenterology, Kyoto Second Red Cross Hospital kn-affil= affil-num=24 en-affil=Department of Internal Medicine, Toyama Prefectural Central Hospital kn-affil= affil-num=25 en-affil=First Department of Internal Medicine, Gifu University Hospital kn-affil= affil-num=26 en-affil=Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine kn-affil= affil-num=27 en-affil=Department of Gastroenterology and Hepatology, Tokyo Medical University kn-affil= en-keyword=ERCP kn-keyword=ERCP en-keyword=guidewire kn-keyword=guidewire en-keyword=pancreatitis kn-keyword=pancreatitis en-keyword=post-ERCP pancreatitis kn-keyword=post-ERCP pancreatitis en-keyword=wire-guided cannulation kn-keyword=wire-guided cannulation END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=12 article-no= start-page=1584 end-page=1595 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250906 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Combination chemotherapy for older patients with unresectable biliary tract cancer: a prospective observational study using propensity-score matched analysis (JON2104-B) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Systemic chemotherapy with gemcitabine plus S-1 (GEM + S-1), GEM + CDDP plus S-1 (GEM + CDDP + S-1), or gemcitabine plus cisplatin (GEM + CDDP) is standard treatment for advanced biliary tract cancer (aBTC). We aimed to evaluate the efficacy and safety of combination chemotherapy in older patients with aBTC.
Methods: This multicenter prospective observational study (JON2104-B, UMIN000045156) included patients aged ≥ 70 years with aBTC. Inverse-probability weighting propensity-score analyses (IPW) were used to compare overall survival (OS) as the primary endpoint and progression-free survival (PFS) across treatment groups.
Results: This study included 305 patients between August 2021 and January 2023. Of them, 75, 131, 26, 52, and 10 received GEM + CDDP + S-1, GEM + CDDP, GEM + S-1, gemcitabine, and S-1; their median ages were 74, 75, 77.5, 80, and 80 years, and approximately 24%, 16.8%, 23.1%, 9.6%, and 0% had G-8 scores of > 14, respectively. GEM + CDDP had a safety profile comparable to that of GEM + CDDP + S-1 but was more toxic than gemcitabine. Per IPW, the hazard ratio (HR) for GEM + CDDP + S-1 versus GEM + CDDP was 0.80 for OS (95% confidence interval [CI], 0.55–1.17) and 0.55 for PFS (95% CI 0.38–0.80). The HR for GEM + CDDP versus gemcitabine was 0.74 for OS (95% CI 0.42–1.29) and 0.79 for PFS (95% CI 0.42–1.49).
Conclusions: GEM + CDDP + S-1 was associated with longer PFS without additional toxicity than GEM + CDDP for fit older patients. However, the OS for both were not statistically different. The efficacies of GEM + CDDP and gemcitabine for vulnerable older patients did not also differ significantly. These findings highlight the importance of vulnerability in patients with aBTC. en-copyright= kn-copyright= en-aut-name=KobayashiSatoshi en-aut-sei=Kobayashi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakachiKohei en-aut-sei=Nakachi en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoKouji en-aut-sei=Yamamoto en-aut-mei=Kouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UenoMakoto en-aut-sei=Ueno en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MarukiYuta en-aut-sei=Maruki en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkezawaKenji en-aut-sei=Ikezawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TerashimaTakeshi en-aut-sei=Terashima en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuSatoshi en-aut-sei=Shimizu en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OshimaKotoe en-aut-sei=Oshima en-aut-mei=Kotoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsujiKunihiro en-aut-sei=Tsuji en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MasakiYoshiharu en-aut-sei=Masaki en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TsumuraHidetaka en-aut-sei=Tsumura en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShibukiTaro en-aut-sei=Shibuki en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OzakaMasato en-aut-sei=Ozaka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OkanoNaohiro en-aut-sei=Okano en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OkamuraYukiyasu en-aut-sei=Okamura en-aut-mei=Yukiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UmemotoKumiko en-aut-sei=Umemoto en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SatohTatsunori en-aut-sei=Satoh en-aut-mei=Tatsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KojimaYasushi en-aut-sei=Kojima en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ShiojiKazuhiko en-aut-sei=Shioji en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NebikiHiroko en-aut-sei=Nebiki en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=DoiToshifumi en-aut-sei=Doi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=NaganumaAtsushi en-aut-sei=Naganuma en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KataokaShigeki en-aut-sei=Kataoka en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KitaEmiri en-aut-sei=Kita en-aut-mei=Emiri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=AsamaHiroyuki en-aut-sei=Asama en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TsuchiyaKaoru en-aut-sei=Tsuchiya en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=UnnoMichiaki en-aut-sei=Unno en-aut-mei=Michiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=AshidaReiko en-aut-sei=Ashida en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=OhnoIzumi en-aut-sei=Ohno en-aut-mei=Izumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=ItoiTakao en-aut-sei=Itoi en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=NegoroYuji en-aut-sei=Negoro en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=SakamotoYasunari en-aut-sei=Sakamoto en-aut-mei=Yasunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=ArimaShiho en-aut-sei=Arima en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=AsagiAkinori en-aut-sei=Asagi en-aut-mei=Akinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=OkuyamaHiroyuki en-aut-sei=Okuyama en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=KomatsuYoshito en-aut-sei=Komatsu en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=KobayashiNoritoshi en-aut-sei=Kobayashi en-aut-mei=Noritoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=NaganoHiroaki en-aut-sei=Nagano en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=FuruseJunji en-aut-sei=Furuse en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= affil-num=1 en-affil=Department of Gastroenterology, Kanagawa Cancer Center kn-affil= affil-num=2 en-affil=Department of Medical Oncology, Tochigi Cancer Center kn-affil= affil-num=3 en-affil=Department of Biostatistics, Yokohama City University School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Kanagawa Cancer Center kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil=Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Kanazawa University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Kanazawa University Hospital kn-affil= affil-num=9 en-affil=Division of Gastrointestinal Oncology, Shizuoka Cancer Center kn-affil= affil-num=10 en-affil=Department of Gastroenterology, Ishikawa Prefectural Central Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine kn-affil= affil-num=12 en-affil=Department of Gastroenterological Oncology, Hyogo Cancer Center kn-affil= affil-num=13 en-affil=Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East kn-affil= affil-num=14 en-affil=Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=15 en-affil=Department of Medical Oncology, Kyorin University Faculty of Medicine kn-affil= affil-num=16 en-affil=Division of Digestive Surgery, Department of Surgery, Nihon University School of Medicine kn-affil= affil-num=17 en-affil=Department of Clinical Oncology, St. Marianna University School of Medicine kn-affil= affil-num=18 en-affil=Department of Gastroenterology, Shizuoka General Hospital kn-affil= affil-num=19 en-affil=Department of Gastroenterology, National Center for Global Health and Medicine kn-affil= affil-num=20 en-affil=Department of Gastroenterology, Niigata Cancer Center Hospital kn-affil= affil-num=21 en-affil=Department of Gastroenterology, Osaka City General Hospital kn-affil= affil-num=22 en-affil=Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine kn-affil= affil-num=23 en-affil=Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center kn-affil= affil-num=24 en-affil=Department of Clinical Oncology, Graduate School of Medicine Faculty of Medicine, Kyoto University kn-affil= affil-num=25 en-affil=Department of Gastroenterology, Chiba Cancer Center kn-affil= affil-num=26 en-affil=Department of Gastroenterology, Fukushima Medical University kn-affil= affil-num=27 en-affil=Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital kn-affil= affil-num=28 en-affil=Department of Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=29 en-affil=Second Department of Internal Medicine, Wakayama Medical University kn-affil= affil-num=30 en-affil=Department of Gastroenterology, Okayama University Graduate School of Medicine kn-affil= affil-num=31 en-affil=Department of Gastroenterology, Chiba University Graduate School of Medicine kn-affil= affil-num=32 en-affil=Department of Gastroenterology, Tokyo Medical University kn-affil= affil-num=33 en-affil=Department of Oncologial Medicine, Kochi Health Sciences Center kn-affil= affil-num=34 en-affil=Department of Gastroenterology and Hepatology, International University of Health and Welfare Atami Hospital kn-affil= affil-num=35 en-affil=Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=36 en-affil=Department of Gastroenterology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=37 en-affil=Department of Medical Oncology, Kagawa University Hospital kn-affil= affil-num=38 en-affil=Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center kn-affil= affil-num=39 en-affil=Department of Oncology, School of Medicine Graduate School of Medicine, Yokohama City University kn-affil= affil-num=40 en-affil=Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=41 en-affil=Department of Gastroenterology, Kanagawa Cancer Center kn-affil= en-keyword=Biliary tract cancer kn-keyword=Biliary tract cancer en-keyword=Unresectable kn-keyword=Unresectable en-keyword=Chemotherapy kn-keyword=Chemotherapy en-keyword=Older kn-keyword=Older en-keyword=Survival kn-keyword=Survival END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mortality and cancer risk in patients with chronic pancreatitis in japan: insights into the importance of surveillance for pancreatic cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objective: Since the 2010s, Japan’s national health insurance system has covered key management for chronic pancreatitis (CP), including pancreatic enzyme replacement therapy. These therapies are expected to improve long-term prognosis; however, recent data are lacking. This study aimed to clarify the updated cancer risk and mortality among patients with CP in Japan.
Methods: We conducted a multicenter, retrospective cohort study on 1,110 patients with CP treated at 28 institutions in 2011. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were calculated for comorbidities. Factors associated with the development of malignancy and overall survival were analyzed.
Results: Patients with CP had an elevated SIR of 1.62 (95% confidence interval [CI], 1.43–1.83) for malignancy, with the highest risk observed for pancreatic cancer (SIR = 6.44 [95% CI, 4.64–8.90]). During follow-up, 143 patients (12.9%) died, most frequently from malignancy (47.5%). The SMR was elevated in all patients with CP (SMR = 1.20 [95% CI, 1.01–1.42]) and in those with alcohol-related CP (SMR = 1.49 [95% CI, 1.23–1.81]) but not in those with alcohol-unrelated CP. Pancreatic cancer was identified as the strongest factor associated with overall survival (hazard ratio, 48.92 in multivariate analysis). Overall survival of the patients with pancreatic cancer was significantly longer in those who underwent regular examinations for CP at least every three months (P = 0.011).
Conclusions: Patients with alcohol-related CP have higher mortality than the general population in Japan. Pancreatic cancer remains a crucial prognostic factor in patients with CP. Regular surveillance for pancreatic cancer is important to improve their prognosis. en-copyright= kn-copyright= en-aut-name=MatsumotoRyotaro en-aut-sei=Matsumoto en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikutaKazuhiro en-aut-sei=Kikuta en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakikawaTetsuya en-aut-sei=Takikawa en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakaiYousuke en-aut-sei=Nakai en-aut-mei=Yousuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakenakaMamoru en-aut-sei=Takenaka en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkiKentaro en-aut-sei=Oki en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhnoEizaburo en-aut-sei=Ohno en-aut-mei=Eizaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ItoKen en-aut-sei=Ito en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujimoriNao en-aut-sei=Fujimori en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatanumaAkio en-aut-sei=Katanuma en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MasudaAtsuhiro en-aut-sei=Masuda en-aut-mei=Atsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HoriYasuki en-aut-sei=Hori en-aut-mei=Yasuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IkeuraTsukasa en-aut-sei=Ikeura en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SuzukiRei en-aut-sei=Suzuki en-aut-mei=Rei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamamotoSatoshi en-aut-sei=Yamamoto en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SogameYoshio en-aut-sei=Sogame en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KawashimaHiroki en-aut-sei=Kawashima en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ItoTetsuhide en-aut-sei=Ito en-aut-mei=Tetsuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OkuwakiKosuke en-aut-sei=Okuwaki en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ItoiTakao en-aut-sei=Itoi en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TakayamaYukiko en-aut-sei=Takayama en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=NakamuraAkira en-aut-sei=Nakamura en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TeraiShuji en-aut-sei=Terai en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KuwataniMasaki en-aut-sei=Kuwatani en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KishiwadaMasashi en-aut-sei=Kishiwada en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ShigekawaMinoru en-aut-sei=Shigekawa en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MatsumoriTomoaki en-aut-sei=Matsumori en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=InatomiOsamu en-aut-sei=Inatomi en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=HattaWaku en-aut-sei=Hatta en-aut-mei=Waku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=IrisawaAtsushi en-aut-sei=Irisawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=UnnoMichiaki en-aut-sei=Unno en-aut-mei=Michiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=TakeyamaYoshifumi en-aut-sei=Takeyama en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=MasamuneAtsushi en-aut-sei=Masamune en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=Japan Pancreatitis Study Group for Chronic Pancreatitis en-aut-sei=Japan Pancreatitis Study Group for Chronic Pancreatitis en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= affil-num=1 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Kurashiki Central Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine kn-affil= affil-num=8 en-affil=Division of Gastroenterology and Hepatology, Toho University Omori Medical Center kn-affil= affil-num=9 en-affil=Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=10 en-affil=Center for Gastroenterology, Teine-Keijinkai Hospital kn-affil= affil-num=11 en-affil=Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Kansai Medical University kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Fukushima Medical University School of Medicine kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Fujita Health University Bantane Hospital kn-affil= affil-num=16 en-affil=Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, International University of Health and Welfare kn-affil= affil-num=19 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=20 en-affil=Department of Gastroenterology and Hepatology, Tokyo Medical University kn-affil= affil-num=21 en-affil=Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University kn-affil= affil-num=22 en-affil=Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine kn-affil= affil-num=23 en-affil=Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=24 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=25 en-affil=Department of Gastroenterology and Hepatology, Hokkaido University Hospital kn-affil= affil-num=26 en-affil=Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine kn-affil= affil-num=27 en-affil=Department of Gastroenterology and Hepatology, The University of Osaka Graduate School of Medicine kn-affil= affil-num=28 en-affil=Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine kn-affil= affil-num=29 en-affil=Department of Medicine, Shiga University of Medical Science kn-affil= affil-num=30 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=31 en-affil=Department of Gastroenterology, Dokkyo Medical University School of Medicine kn-affil= affil-num=32 en-affil=Department of Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=33 en-affil=Department of Surgery, Kindai University Faculty of Medicine kn-affil= affil-num=34 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=35 en-affil= kn-affil= en-keyword=Alcohol kn-keyword=Alcohol en-keyword=Chronic pancreatitis kn-keyword=Chronic pancreatitis en-keyword=Pancreatic cancer kn-keyword=Pancreatic cancer en-keyword=Pancreatitis kn-keyword=Pancreatitis en-keyword=Smoking kn-keyword=Smoking END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=2586329 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251130 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Asiatic acid, a novel ciprofloxacin adjuvant inhibits Shigella flexneri infection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bacterial infection caused by intracellular pathogens such as Shigella flexneri is a rapidly increasing global health concern that requires urgent and necessary action. The dearth of licensed vaccines against shigellosis and the decline in susceptibility to conventional antibiotics has encouraged the development of new antibiotic principles and drugs. The treatment options are decreasing faster than the discovery rate of new antibacterial agents. Combinatorial approach of antibiotics with non-antibiotic adjuvants is a promising aspect to treat resistant bacterial infections. Asiatic acid, a membrane-disrupting triterpenoid with wide antimicrobial and immunomodulatory properties, can potentiate antibiotics, but the exact mechanisms remain broadly unexplored. Therefore, in this study, we screened the interaction of asiatic acid with several antibiotics. The results showed synergistic interactions of asiatic acid with antibiotics against susceptible and multidrug-resistant S. flexneri clinical isolates. Particularly important was the interaction of asiatic acid with the quinolone antibiotics ciprofloxacin and nalidixic acid. A detailed study showed that combined treatment of asiatic acid with ciprofloxacin inhibited S. flexneri biofilm formation and resistance development. An increase in membrane disruption and depolarization upon co-treatment was evident by surface electron and confocal microscopy. In addition, asiatic acid and ciprofloxacin synergism was identified to inhibit efflux activity and intracellular bacterial viability. However, asiatic acid showed no synergistic toxicity with ciprofloxacin towards mammalian cells. The antibacterial activity was further verified in a S. flexneri infected mice model. Therapeutic benefits were evident with reduced bacterial burden, recovery from intestinal tissue damage and increase in mice survivability. The results showed that this combination can target the bacterial membrane, efflux pump proteins and biofilm formation, thereby preventing resistance development. The combination treatment offers a proof of concept in targeting essential bacterial activities and might be developed into a novel and efficient treatment alternative against S. flexneri. en-copyright= kn-copyright= en-aut-name=MaitraPriyanka en-aut-sei=Maitra en-aut-mei=Priyanka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BhuktaSamhati en-aut-sei=Bhukta en-aut-mei=Samhati kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GopeAnimesh en-aut-sei=Gope en-aut-mei=Animesh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KayetPratanu en-aut-sei=Kayet en-aut-mei=Pratanu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BasakSurajit en-aut-sei=Basak en-aut-mei=Surajit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyoshiShin-Ichi en-aut-sei=Miyoshi en-aut-mei=Shin-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KitaharaKei en-aut-sei=Kitahara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=DuttaShanta en-aut-sei=Dutta en-aut-mei=Shanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BhattacharyaSushmita en-aut-sei=Bhattacharya en-aut-mei=Sushmita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=2 en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=3 en-affil=Division of Clinical Medicine, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=4 en-affil=Division of Bioinformatics, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=5 en-affil=Division of Bioinformatics, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=6 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Collaborative Research Center of Okayama University for Infectious Diseases in India, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=8 en-affil=Department of Bacteriology, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=9 en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections kn-affil= en-keyword=Shigella flexneri kn-keyword=Shigella flexneri en-keyword=asiatic acid kn-keyword=asiatic acid en-keyword=ciprofloxacin kn-keyword=ciprofloxacin en-keyword=adjuvant kn-keyword=adjuvant en-keyword=membrane damage kn-keyword=membrane damage en-keyword=depolarization kn-keyword=depolarization en-keyword=nuclear damage kn-keyword=nuclear damage en-keyword=efflux inhibitor kn-keyword=efflux inhibitor END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=19 article-no= start-page=3144 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250927 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Utility of Same-Modality, Cross-Domain Transfer Learning for Malignant Bone Tumor Detection on Radiographs: A Multi-Faceted Performance Comparison with a Scratch-Trained Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Developing high-performance artificial intelligence (AI) models for rare diseases like malignant bone tumors is limited by scarce annotated data. This study evaluates same-modality cross-domain transfer learning by comparing an AI model pretrained on chest radiographs with a model trained from scratch for detecting malignant bone tumors on knee radiographs. Methods: Two YOLOv5-based detectors differed only in initialization (transfer vs. scratch). Both were trained/validated on institutional data and tested on an independent external set of 743 radiographs (268 malignant, 475 normal). The primary outcome was AUC; prespecified operating points were high-sensitivity (≥0.90), high-specificity (≥0.90), and Youden-optimal. Secondary analyses included PR/F1, calibration (Brier, slope), and decision curve analysis (DCA). Results: AUC was similar (YOLO-TL 0.954 [95% CI 0.937–0.970] vs. YOLO-SC 0.961 [0.948–0.973]; DeLong p = 0.53). At the high-sensitivity point (both sensitivity = 0.903), YOLO-TL achieved higher specificity (0.903 vs. 0.867; McNemar p = 0.037) and PPV (0.840 vs. 0.793; bootstrap p = 0.030), reducing ~17 false positives among 475 negatives. At the high-specificity point (~0.902–0.903 for both), YOLO-TL showed higher sensitivity (0.798 vs. 0.764; p = 0.0077). At the Youden-optimal point, sensitivity favored YOLO-TL (0.914 vs. 0.892; p = 0.041) with a non-significant specificity difference. Conclusions: Transfer learning may not improve overall AUC but can enhance practical performance at clinically crucial thresholds. By maintaining high detection rates while reducing false positives, the transfer learning model offers superior clinical utility. Same-modality cross-domain transfer learning is an efficient strategy for developing robust AI systems for rare diseases, supporting tools more readily acceptable in real-world screening workflows. en-copyright= kn-copyright= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaharaRyuichi en-aut-sei=Nakahara en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaYujiro en-aut-sei=Otsuka en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakeuchiKoichi en-aut-sei=Takeuchi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraYusuke en-aut-sei=Nakamura en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkutaKunihiro en-aut-sei=Ikuta en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OsakiShuhei en-aut-sei=Osaki en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TamiyaHironari en-aut-sei=Tamiya en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiwaShinji en-aut-sei=Miwa en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhshikaShusa en-aut-sei=Ohshika en-aut-mei=Shusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NishimuraShunji en-aut-sei=Nishimura en-aut-mei=Shunji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KaharaNaoaki en-aut-sei=Kahara en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KondoHiroya en-aut-sei=Kondo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Medical Informatics and Clinical Support Technology Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiology, Juntendo University School of Medicine kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Plusman LCC kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Graduate School of Medicine, Nagoya University kn-affil= affil-num=7 en-affil=Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Musculoskeletal Oncology Service, Osaka International Cancer Institute, kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery, Kindai University Hospital kn-affil= affil-num=12 en-affil=Department of Orthopedic Surgery, Mizushima Central Hospital kn-affil= affil-num=13 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=malignant bone tumors kn-keyword=malignant bone tumors en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=transfer learning kn-keyword=transfer learning en-keyword=YOLO kn-keyword=YOLO en-keyword=radiographs kn-keyword=radiographs en-keyword=cross-domain learning kn-keyword=cross-domain learning en-keyword=diagnostic imaging kn-keyword=diagnostic imaging END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=6 article-no= start-page=1100 end-page=1111 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relation between obesity and health disorders as revealed by the J-ORBIT clinical information collection system directly linked to electronic medical records (J-ORBIT 1) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims/Introduction: Obesity triggers various health disorders, but information on these disorders in real-world settings remains limited. To address this knowledge gap, we developed a database directly linked to electronic medical records (EMRs). We here present the baseline data for this database, designated Japan Obesity Research Based on electronIc healTh Records (J-ORBIT).
Materials and Methods: Individuals with obesity disease diagnosed according to the criteria of the Japan Society for the Study of Obesity were registered in J-ORBIT from seven medical centers in Japan. We analyzed the relationship between body mass index (BMI), clinical characteristics, and the prevalence of obesity-related health disorders in this cohort.
Results: Data were obtained from 1,169 individuals, with a mean (±SD) age of 56.9 ± 15.3 years and a BMI of 31.4 ± 6.1 kg/m2. The prevalence of health disorders varied substantially across BMI categories, with a higher BMI being associated with an increased prevalence of hyperuricemia or gout, obstructive sleep apnea syndrome or obesity hypoventilation syndrome, musculoskeletal disorders, and obesity-related kidney disease, as well as with a higher frequency of both a family history of obesity and of a history of childhood obesity. Among individuals with a BMI of ≥25 kg/m2, the prevalence of hypertension and dyslipidemia did not increase with BMI, whereas that of glucose intolerance decreased with increasing BMI.
Conclusions: The J-ORBIT system, which collects clinical data in real time directly from EMRs, has the potential to provide insight into obesity and its associated health conditions, thereby contributing to improved care of affected individuals. en-copyright= kn-copyright= en-aut-name=NishikageSeiji en-aut-sei=Nishikage en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HirotaYushi en-aut-sei=Hirota en-aut-mei=Yushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakagawaYasushi en-aut-sei=Nakagawa en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshiiMasamichi en-aut-sei=Ishii en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhsugiMitsuru en-aut-sei=Ohsugi en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaedaEiichi en-aut-sei=Maeda en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshimuraKai en-aut-sei=Yoshimura en-aut-mei=Kai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoAkane en-aut-sei=Yamamoto en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakayoshiTomofumi en-aut-sei=Takayoshi en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatoTakehiro en-aut-sei=Kato en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YabeDaisuke en-aut-sei=Yabe en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsuhisaMunehide en-aut-sei=Matsuhisa en-aut-mei=Munehide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=EguchiJun en-aut-sei=Eguchi en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujitaYukihiro en-aut-sei=Fujita en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KumeShinji en-aut-sei=Kume en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MaegawaHiroshi en-aut-sei=Maegawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MiyakeKana en-aut-sei=Miyake en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShojimaNobuhiro en-aut-sei=Shojima en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YamauchiToshimasa en-aut-sei=Yamauchi en-aut-mei=Toshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YokoteKoutaro en-aut-sei=Yokote en-aut-mei=Koutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=UekiKohjiro en-aut-sei=Ueki en-aut-mei=Kohjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MiyoKengo en-aut-sei=Miyo en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OgawaWataru en-aut-sei=Ogawa en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= affil-num=1 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Center for Medical Informatics Intelligence, National Center for Global Health and Medicine kn-affil= affil-num=5 en-affil=Diabetes and Metabolism Information Center, Research Institute, National Center for Global Health and Medicine kn-affil= affil-num=6 en-affil=Division of Medical Informatics, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Diabetes, Endocrinology, and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Diabetes, Endocrinology, and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University kn-affil= affil-num=13 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Medicine, Shiga University of Medical Science kn-affil= affil-num=16 en-affil=Department of Medicine, Shiga University of Medical Science kn-affil= affil-num=17 en-affil=Department of Medicine, Shiga University of Medical Science kn-affil= affil-num=18 en-affil=Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=21 en-affil=Chiba University kn-affil= affil-num=22 en-affil=Diabetes Research Center, Research Institute, National Center for Global Health and Medicine kn-affil= affil-num=23 en-affil=Center for Medical Informatics Intelligence, National Center for Global Health and Medicine kn-affil= affil-num=24 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= en-keyword=Body mass index kn-keyword=Body mass index en-keyword=Electronic medical records kn-keyword=Electronic medical records en-keyword=Obesity kn-keyword=Obesity END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251019 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of methotrexate-dosing regimens for GVHD prophylaxis on clinical outcomes of HLA-matched allogeneic HSCT en-subtitle= kn-subtitle= en-abstract= kn-abstract=Severe graft-versus-host disease (GVHD) remains a major complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT), necessitating optimal immunosuppressive strategies. This retrospective study used data from the Japanese Transplant Registry Unified Management Program to compare three methotrexate (MTX)-dosing regimens for GVHD prophylaxis in patients undergoing human leucocyte antigen (HLA)-matched allo-HSCT: a low-dose 3-day regimen (Ld3:10 mg/m2 on day 1, 7 mg/m2 on days 3 and 6), a low-dose 4-day regimen (Ld4: Ld3 with an additional 7 mg/m2 on day 11) and an original-dose 3-day regimen (Od3: 15 mg/m2 on day 1, 10 mg/m2 on days 3 and 6). Among 2537 analysed patients, Ld3 was the most commonly used regimen. Multivariate analyses showed no significant differences in the cumulative incidence of grade II–IV acute GVHD among regimens. However, Od3 was associated with an increased risk of grade III–IV acute GVHD, and Ld4 was linked to delayed neutrophil engraftment. This study is the first large-scale retrospective analysis of the impact of different MTX-dosing regimens on the outcomes of HLA-matched allo-HSCT, providing valuable insights into optimal MTX-dosing strategies in clinical practice. en-copyright= kn-copyright= en-aut-name=SuzukiTomotaka en-aut-sei=Suzuki en-aut-mei=Tomotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=JoTomoyasu en-aut-sei=Jo en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshifujiKota en-aut-sei=Yoshifuji en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoTadakazu en-aut-sei=Kondo en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KandaYoshinobu en-aut-sei=Kanda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishidaTetsuya en-aut-sei=Nishida en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OnishiYasushi en-aut-sei=Onishi en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukudaTakahiro en-aut-sei=Fukuda en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SawaMasashi en-aut-sei=Sawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HasegawaYuta en-aut-sei=Hasegawa en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SerizawaKentaro en-aut-sei=Serizawa en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OtaShuichi en-aut-sei=Ota en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaMasatsugu en-aut-sei=Tanaka en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YoshimitsuMakoto en-aut-sei=Yoshimitsu en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KandaJunya en-aut-sei=Kanda en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=3 en-affil=Department of Hematology, Institute of Science Tokyo kn-affil= affil-num=4 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=5 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Centre, Komagome Hospital kn-affil= affil-num=6 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Centre kn-affil= affil-num=7 en-affil=Department of Hematology, Japanese Red Cross Aichi Medical Centre Nagoya Daiichi Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Tohoku University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Haematopoietic Stem Cell Transplantation, National Cancer Centre Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Anjo Kosei Hospital kn-affil= affil-num=12 en-affil=Department of Hematology, Hokkaido University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Rheumatology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Hematology, Sapporo Hokuyu Hospital kn-affil= affil-num=15 en-affil=Department of Hematology, Kanagawa Cancer Centre kn-affil= affil-num=16 en-affil=Department of Hematology and Rheumatology, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=17 en-affil=Japanese Data Centre for Haematopoietic Cell Transplantation kn-affil= affil-num=18 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= en-keyword=allo-HSCT kn-keyword=allo-HSCT en-keyword=dosing regimens kn-keyword=dosing regimens en-keyword=graft-versus-host disease kn-keyword=graft-versus-host disease en-keyword=GVHD prophylaxis kn-keyword=GVHD prophylaxis en-keyword=methotrexate kn-keyword=methotrexate END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=5 article-no= start-page=e70138 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Late‐Onset Invasive Aspergillosis With Pituitary Involvement and Dysfunction Following CD19 Chimeric Antigen Receptor T‐Cell Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Invasive fungal infection (IFI) after chimeric antigen receptor (CAR) T-cell therapy is less common than bacterial and viral infections, but can be fatal once it develops. As most cases occur within 30 days after CAR T-cell infusion, late-onset IFI—particularly mould infection—appears to be under-recognised.
Discussion: We report an illustrative case of pituitary aspergillosis developing as late as one year after CD19 CAR T-cell therapy, highlighting a persistent risk in certain patients with delayed immune reconstitution.
Conclusion: This case underscores the need for continued vigilance and individualised antifungal strategies to prevent IFI beyond the early post-infusion period.
Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission. en-copyright= kn-copyright= en-aut-name=IkedaDaisuke en-aut-sei=Ikeda en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NawadaTomohiro en-aut-sei=Nawada en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShinoharaTakayuki en-aut-sei=Shinohara en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaganoTomohiro en-aut-sei=Nagano en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KubotaSaya en-aut-sei=Kubota en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiyamaRyuichiro en-aut-sei=Hiyama en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UenoMasaya en-aut-sei=Ueno en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MakitaMasanori en-aut-sei=Makita en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=The Center for Graduate Medical Education, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Fungal Infection, National Institute of Infectious Diseases kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology, Chugoku Central Hospital kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=aspergillosis kn-keyword=aspergillosis en-keyword=CD19 CAR T kn-keyword=CD19 CAR T en-keyword=invasive fungal infection kn-keyword=invasive fungal infection en-keyword=pituitary kn-keyword=pituitary END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=18 article-no= start-page=4640 end-page=4653 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250912 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Refinement of day 28 treatment response criteria for acute GVHD: a collaboration study of the JSTCT and MAGIC en-subtitle= kn-subtitle= en-abstract= kn-abstract=Overall response (OR) that combines complete (CR) and partial responses (PR) is the conventional end point for acute graft-versus-host disease (GVHD) trials. Because PR includes heterogeneous clinical presentations, reclassifying PR could produce a better end point. Patients in the primary treatment cohort from the Japanese Society for Transplantation and Cellular Therapy (JSTCT) were randomly divided into training and validation sets. In the training set, a classification and regression tree algorithm generated day 28 refined response (RR) criteria based on symptoms at treatment and day 28. We then evaluated RR for primary and second-line treatments, using the area under the receiver operating characteristic curve (AUC) and negative predictive value (NPV) for 6-month nonrelapse mortality as performance measures. RR considered patients with grade 0/1 at day 28 without additional treatment as responders. RR for primary treatment produced higher AUCs than OR with small improvement of NPVs in both validation sets: JSTCT (AUC, 0.73 vs 0.69 [P < .001]; NPV, 92.0% vs 89.6% [P < .001]) and the Mount Sinai Acute GVHD International Consortium (MAGIC; AUC, 0.71 vs 0.68 [P = .032]; NPV, 90.9% vs 89.8% [P = .009]). RR for second-line treatment produced similar AUCs but much higher NPVs than OR in both validation sets of JSTCT (AUC, 0.64 vs 0.63 [P = .775]; NPV, 74.5% vs 66.0% [P < .001]) and MAGIC (AUC, 0.67 vs 0.64 [P = .105]; NPV, 86.8% vs 76.1% [P = .004]). Classifying persistent but mild skin symptoms as responses and residual lower gastrointestinal GVHD as nonresponses were major drivers in improving the prognostic performance of RR. Our externally validated day 28 RR would serve as a better end point than conventional criteria in future first- and second-line treatment trials. en-copyright= kn-copyright= en-aut-name=AkahoshiYu en-aut-sei=Akahoshi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InamotoYoshihiro en-aut-sei=Inamoto en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SpyrouNikolaos en-aut-sei=Spyrou en-aut-mei=Nikolaos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakasoneHideki en-aut-sei=Nakasone en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DinizMarcio A. en-aut-sei=Diniz en-aut-mei=Marcio A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AyukFrancis en-aut-sei=Ayuk en-aut-mei=Francis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ChoeHannah K. en-aut-sei=Choe en-aut-mei=Hannah K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EtoTetsuya en-aut-sei=Eto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EtraAaron M. en-aut-sei=Etra en-aut-mei=Aaron M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HexnerElizabeth O. en-aut-sei=Hexner en-aut-mei=Elizabeth O. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HiramotoNobuhiro en-aut-sei=Hiramoto en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HoganWilliam J. en-aut-sei=Hogan en-aut-mei=William J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HollerErnst en-aut-sei=Holler en-aut-mei=Ernst kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KataokaKeisuke en-aut-sei=Kataoka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KawakitaToshiro en-aut-sei=Kawakita en-aut-mei=Toshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TanakaMasatsugu en-aut-sei=Tanaka en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TanakaTakashi en-aut-sei=Tanaka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=UchidaNaoyuki en-aut-sei=Uchida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=VasovaIngrid en-aut-sei=Vasova en-aut-mei=Ingrid kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=YoshiharaSatoshi en-aut-sei=Yoshihara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=IshimaruFumihiko en-aut-sei=Ishimaru en-aut-mei=Fumihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=FukudaTakahiro en-aut-sei=Fukuda en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ChenYi-Bin en-aut-sei=Chen en-aut-mei=Yi-Bin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KandaJunya en-aut-sei=Kanda en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=NakamuraRyotaro en-aut-sei=Nakamura en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=FerraraJames L. M. en-aut-sei=Ferrara en-aut-mei=James L. M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=KandaYoshinobu en-aut-sei=Kanda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=LevineJohn E. en-aut-sei=Levine en-aut-mei=John E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=TeshimaTakanori en-aut-sei=Teshima en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= affil-num=1 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=2 en-affil=Department of Blood and Marrow Transplantation and Cellular Therapy, Fujita Health University School of Medicine kn-affil= affil-num=3 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=4 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Center kn-affil= affil-num=5 en-affil=Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf kn-affil= affil-num=8 en-affil=Division of Hematology, Blood and Marrow Transplantation Program, The Ohio State University Comprehensive Cancer Center kn-affil= affil-num=9 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Hamanomachi Hospital kn-affil= affil-num=11 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=12 en-affil=Department of Medicine and Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=13 en-affil=Department of Hematology, Kobe City Medical Center General Hospital kn-affil= affil-num=14 en-affil=Division of Hematology, Mayo Clinic kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Internal Medicine III, University of Regensburg kn-affil= affil-num=16 en-affil=Division of Molecular Oncology, National Cancer Center Research Institute kn-affil= affil-num=17 en-affil=Department of Hematology, National Hospital Organization Kumamoto Medical Center kn-affil= affil-num=18 en-affil=Department of Hematology, Kanagawa Cancer Center kn-affil= affil-num=19 en-affil=Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital kn-affil= affil-num=20 en-affil=Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital kn-affil= affil-num=21 en-affil=Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg and University Hospital Erlangen kn-affil= affil-num=22 en-affil=Department of Hematology, Hyogo Medical University Hospital kn-affil= affil-num=23 en-affil=Technical Department, Japanese Red Cross Blood Service Headquarters kn-affil= affil-num=24 en-affil=Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital kn-affil= affil-num=25 en-affil=Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital kn-affil= affil-num=26 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=27 en-affil=Department of Hematology and Hematopoietic Cell Transplantation, City of Hope kn-affil= affil-num=28 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=29 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=30 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Center kn-affil= affil-num=31 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=32 en-affil=Department of Hematology, Hokkaido University Faculty of Medicine and Graduate School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2024 for the clinical practice of hereditary colorectal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Approximately 5% of all colorectal cancers have a strong genetic component and are classified as hereditary colorectal cancer (HCRC). Some of the unique features commonly seen in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics require different management approaches, including diagnosis, treatment or surveillance, from those used in the management of sporadic colorectal cancer. Accurate diagnosis of HCRC is essential because it enables targeted surveillance and risk reduction strategies that improve patient outcomes. Recent genetic advances revealed several causative genes for polyposis and non-polyposis syndromes. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) first published guidelines for the management of HCRC in 2012, with subsequent revisions every 4 years. The 2024 update to the JSCCR guidelines for HCRC was developed by meticulously reviewing evidence from systematic reviews and the consensus of the JSCCR HCRC Guidelines Committee, which includes representatives from patient advocacy groups for FAP and Lynch syndrome. These guidelines provide an up-to-date summary of HCRC, along with clinical recommendations for managing FAP and Lynch syndrome. en-copyright= kn-copyright= en-aut-name=TanakayaKohji en-aut-sei=Tanakaya en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamaguchiTatsuro en-aut-sei=Yamaguchi en-aut-mei=Tatsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirataKeiji en-aut-sei=Hirata en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamadaMasayoshi en-aut-sei=Yamada en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KumamotoKensuke en-aut-sei=Kumamoto en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkiyamaYasuki en-aut-sei=Akiyama en-aut-mei=Yasuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshimaruKei en-aut-sei=Ishimaru en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoKoichi en-aut-sei=Okamoto en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawasakiYuko en-aut-sei=Kawasaki en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KomineKeigo en-aut-sei=Komine en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakamotoAkira en-aut-sei=Sakamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShibataYoshiko en-aut-sei=Shibata en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShimamotoYusaku en-aut-sei=Shimamoto en-aut-mei=Yusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShimodairaHideki en-aut-sei=Shimodaira en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SekineShigeki en-aut-sei=Sekine en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakaoAkinari en-aut-sei=Takao en-aut-mei=Akinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TakaoMisato en-aut-sei=Takao en-aut-mei=Misato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TakamizawaYasuyuki en-aut-sei=Takamizawa en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakeuchiYoji en-aut-sei=Takeuchi en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TanabeNoriko en-aut-sei=Tanabe en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=TaniguchiFumitaka en-aut-sei=Taniguchi en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=ChinoAkiko en-aut-sei=Chino en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=ChoHourin en-aut-sei=Cho en-aut-mei=Hourin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=DoiSatoru en-aut-sei=Doi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=NakajimaTakeshi en-aut-sei=Nakajima en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=NakamoriSakiko en-aut-sei=Nakamori en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NakayamaYoshiko en-aut-sei=Nakayama en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=NagasakiToshiya en-aut-sei=Nagasaki en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=HasumiHisashi en-aut-sei=Hasumi en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=BannoKouji en-aut-sei=Banno en-aut-mei=Kouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=HinoiTakao en-aut-sei=Hinoi en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=FujiyoshiKenji en-aut-sei=Fujiyoshi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=HorimatsuTakahiro en-aut-sei=Horimatsu en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=MasudaKenta en-aut-sei=Masuda en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=MiguchiMasashi en-aut-sei=Miguchi en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=MizuuchiYusuke en-aut-sei=Mizuuchi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=MiyakuraYasuyuki en-aut-sei=Miyakura en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=MutohMichihiro en-aut-sei=Mutoh en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=YoshiokaTakahiro en-aut-sei=Yoshioka en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=TanakaShinji en-aut-sei=Tanaka en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=SakamotoKazuhiro en-aut-sei=Sakamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=SakamakiKentaro en-aut-sei=Sakamaki en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=ItabashiMichio en-aut-sei=Itabashi en-aut-mei=Michio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=IshidaHideyuki en-aut-sei=Ishida en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=TomitaNaohiro en-aut-sei=Tomita en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=SugiharaKenichi en-aut-sei=Sugihara en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=AjiokaYoichi en-aut-sei=Ajioka en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= affil-num=1 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=2 en-affil=Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=3 en-affil=Department of Surgery 1, University of Occupational and Environmental Health kn-affil= affil-num=4 en-affil=Endoscopy Division, National Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Genome Medical Science and Medical Genetics, Faculty of Medicine, Kagawa University kn-affil= affil-num=6 en-affil=Department of Surgery 1, University of Occupational and Environmental Health kn-affil= affil-num=7 en-affil=Division of Gastrointestinal Surgery and Surgical Oncology, Graduate School of Medicine, Ehime University kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science kn-affil= affil-num=9 en-affil=College of Nursing, University of Hyogo kn-affil= affil-num=10 en-affil=Department of Medical Oncology, Tohoku University Hospital kn-affil= affil-num=11 en-affil=Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Himawari-No-Kai (Sunflower Association), a Patient Advocacy Group for Individuals and Families Affected By Lynch Syndrome kn-affil= affil-num=14 en-affil=Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Division of Medical Oncology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University kn-affil= affil-num=16 en-affil=Department of Pathology, Keio University School of Medicine kn-affil= affil-num=17 en-affil=Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=18 en-affil=Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=19 en-affil=Department of Colorectal Surgery, National Cancer Center Hospital kn-affil= affil-num=20 en-affil=Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Clinical Genetics, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=22 en-affil=Department of Surgery, Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=23 en-affil=Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research kn-affil= affil-num=24 en-affil=Endoscopy Center, Tokyo Medical University Hospital kn-affil= affil-num=25 en-affil=Harmony Line (Association for Patients and Families With Familial Adenomatous Polyposis) kn-affil= affil-num=26 en-affil=Division of Hereditary Tumors, Department of Genetic Oncology, Osaka International Cancer Institute kn-affil= affil-num=27 en-affil=Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=28 en-affil=Department of Pediatrics, Shinshu University School of Medicine kn-affil= affil-num=29 en-affil=Department of Gastroenterological Surgery, Saitama Cancer Center kn-affil= affil-num=30 en-affil=Department of Urology, Yokohama City University kn-affil= affil-num=31 en-affil=Center of Maternal -Fetal/Neonatal Medicine, Hiroshima University Hospital kn-affil= affil-num=32 en-affil=Department of Clinical and Molecular Genetics, Hiroshima University Hospital kn-affil= affil-num=33 en-affil=Department of Surgery, Kurume University School of Medicine kn-affil= affil-num=34 en-affil=Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital kn-affil= affil-num=35 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=36 en-affil=Department of Gastroenterological Surgery, Hiroshima Prefectural Hospital kn-affil= affil-num=37 en-affil=Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=38 en-affil=Department of Colon and Pelvic Surgery, Cancer Prevention and Genetic Counseling, Tochigi Cancer Center kn-affil= affil-num=39 en-affil=Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=40 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=41 en-affil=JA Onomichi General Hospital kn-affil= affil-num=42 en-affil=Koshigaya Municipal Hospital kn-affil= affil-num=43 en-affil=Faculty of Health Data Science, Juntendo University kn-affil= affil-num=44 en-affil=Saiseikai Kazo Hospital kn-affil= affil-num=45 en-affil=Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=46 en-affil=Division of Cancer Treatment , Toyonaka Municipal Hospital kn-affil= affil-num=47 en-affil=Institute of Science Tokyo kn-affil= affil-num=48 en-affil=Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= en-keyword=Hereditary colorectal cancer kn-keyword=Hereditary colorectal cancer en-keyword=Guidelines kn-keyword=Guidelines en-keyword=Familial adenomatous polyposis kn-keyword=Familial adenomatous polyposis en-keyword=Lynch syndrome kn-keyword=Lynch syndrome END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=7 article-no= start-page=002115 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) from the Fungal and Protist Viruses Subcommittee, 2025 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The Fungal and Protist Viruses Subcommittee (SC) of the International Committee on Taxonomy of Viruses (ICTV) has received a total of eight taxonomic proposals for the 2024 annual cycle. The extent of proposed changes varied, including nomenclatural updates, creation of new taxa and reorganization of established taxa. Following the ICTV procedures, all proposals were reviewed and voted upon by the members of the Executive Committee with ratification in March 2025. As a result, a total of 52 species in the families Botourmiaviridae and Marnaviridae were renamed to comply with the mandated binomial format. A new genus has been added to the dsRNA virus family Amalgaviridae, while two new families, Splipalmiviridae (Wolframvirales) and Mycoalphaviridae (Hepelivirales), were created to classify new groups of positive-sense (+) RNA mycoviruses. The class Arfiviricetes (Cressdnaviricota) was expanded by a new order Lineavirales and a new family Oomyviridae of ssDNA viruses. Additionally, a new class Orpoviricetes was created in the kingdom Orthornavirae to classify a group of bisegmented (+)RNA viruses reported from fungi and oomycetes. Finally, the order Pimascovirales was reorganized to better depict evolutionary relationships of pithoviruses and related viruses with large dsDNA genomes. The summary of updates in the taxonomy of fungal and protist viruses presented here is limited to taxa within the remit of this Subcommittee. For information on taxonomy changes on other fungal viruses closely related to animal and/or plant viruses, please see reports from sister ICTV Subcommittees (i.e. Plant Virus SC and Animal dsRNA and ssRNA(−) Viruses SC). en-copyright= kn-copyright= en-aut-name=SabanadzovicSead en-aut-sei=Sabanadzovic en-aut-mei=Sead kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AbergelChantal en-aut-sei=Abergel en-aut-mei=Chantal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AyllónMarı́a A. en-aut-sei=Ayllón en-aut-mei=Marı́a A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BotellaLeticia en-aut-sei=Botella en-aut-mei=Leticia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CanutiMarta en-aut-sei=Canuti en-aut-mei=Marta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ChibaYuto en-aut-sei=Chiba en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ClaverieJean-Michel en-aut-sei=Claverie en-aut-mei=Jean-Michel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CouttsRobert H.A. en-aut-sei=Coutts en-aut-mei=Robert H.A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DaghinoStefania en-aut-sei=Daghino en-aut-mei=Stefania kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=DonaireLivia en-aut-sei=Donaire en-aut-mei=Livia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ForgiaMarco en-aut-sei=Forgia en-aut-mei=Marco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HejnaOndřej en-aut-sei=Hejna en-aut-mei=Ondřej kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=JiaJichun en-aut-sei=Jia en-aut-mei=Jichun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=JiangDaohong en-aut-sei=Jiang en-aut-mei=Daohong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=Kotta-LoizouIoly en-aut-sei=Kotta-Loizou en-aut-mei=Ioly kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KrupovicMart en-aut-sei=Krupovic en-aut-mei=Mart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=LangAndrew S. en-aut-sei=Lang en-aut-mei=Andrew S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=LegendreMatthieu en-aut-sei=Legendre en-aut-mei=Matthieu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=Lee MarzanoShin-Yi en-aut-sei=Lee Marzano en-aut-mei=Shin-Yi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=NervaLuca en-aut-sei=Nerva en-aut-mei=Luca kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=PénzesJudit en-aut-sei=Pénzes en-aut-mei=Judit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=PoimalaAnna en-aut-sei=Poimala en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=RigouSofia en-aut-sei=Rigou en-aut-mei=Sofia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=SatoYukiyo en-aut-sei=Sato en-aut-mei=Yukiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ShamsiWajeeha en-aut-sei=Shamsi en-aut-mei=Wajeeha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TurinaMassimo en-aut-sei=Turina en-aut-mei=Massimo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=UrayamaSyun-ichi en-aut-sei=Urayama en-aut-mei=Syun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=VainioEeva J. en-aut-sei=Vainio en-aut-mei=Eeva J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=XieJiatao en-aut-sei=Xie en-aut-mei=Jiatao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University kn-affil= affil-num=2 en-affil=Information Génomique & Structurale, UMR7256, CNRS & Aix-Marseille Université, Marseille, IMM, IM2B, IOM kn-affil= affil-num=3 en-affil=Departamento de Biotecnología-Biología Vegetal, Escuela Técnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas, Universidad Politécnica de Madrid (UPM) kn-affil= affil-num=4 en-affil=Forest Protection and Wildlife Management Mendel University in Brno kn-affil= affil-num=5 en-affil=Department of Veterinary and Animal Sciences, University of Copenhagen kn-affil= affil-num=6 en-affil=School of Agriculture, Meiji University kn-affil= affil-num=7 en-affil=Information Génomique & Structurale, UMR7256, CNRS & Aix-Marseille Université, Marseille, IMM, IM2B, IOM kn-affil= affil-num=8 en-affil=School of Health, Medicine and Life Sciences, University of Hertfordshire kn-affil= affil-num=9 en-affil=Institute for Sustainable Plant Protection, National Research Council of Italy kn-affil= affil-num=10 en-affil=Centro de Edafología y Biología Aplicada del Segura-CSIC kn-affil= affil-num=11 en-affil=Institute for Sustainable Plant Protection, CNR kn-affil= affil-num=12 en-affil=Department of Genetics and Biotechnologies, University of South Bohemia kn-affil= affil-num=13 en-affil=College of Plant Protection, Shanxi Agricultural University kn-affil= affil-num=14 en-affil=College of Plant Science and Technology, Huazhong Agricultural University kn-affil= affil-num=15 en-affil=School of Health, Medicine and Life Sciences, University of Hertfordshire kn-affil= affil-num=16 en-affil=Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit kn-affil= affil-num=17 en-affil=Department of Biology, Memorial University of Newfoundland kn-affil= affil-num=18 en-affil=Information Génomique & Structurale, UMR7256, CNRS & Aix-Marseille Université, Marseille, IMM, IM2B, IOM kn-affil= affil-num=19 en-affil=United States Department of Agriculture, Agricultural Research Service, Application Technology Research Unit kn-affil= affil-num=20 en-affil=Council for Agricultural Research and Economics - Research Centre for Viticulture and Enology kn-affil= affil-num=21 en-affil=Department of Entomology, Texas A&M University kn-affil= affil-num=22 en-affil=Natural Resources Institute Finland (Luke) kn-affil= affil-num=23 en-affil=Information Génomique & Structurale, UMR7256, CNRS & Aix-Marseille Université, Marseille, IMM, IM2B, IOM kn-affil= affil-num=24 en-affil=Department of Biology, Institute for Plant Sciences, University of Cologne kn-affil= affil-num=25 en-affil=Department of Molecular Biology and Genetics, Aarhus University kn-affil= affil-num=26 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=27 en-affil=Department of Plant Protection, School of Agriculture, The University of Jordan kn-affil= affil-num=28 en-affil=Department of Life and Environmental Sciences, University of Tsukuba kn-affil= affil-num=29 en-affil=Natural Resources Institute Finland (Luke) kn-affil= affil-num=30 en-affil=College of Plant Science and Technology, Huazhong Agricultural University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=7 article-no= start-page=002079 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Virus taxonomy proposal summaries: a searchable and citable resource to disseminate virus taxonomy advances en-subtitle= kn-subtitle= en-abstract= kn-abstract=Taxonomic classification of cellular organisms requires the publication of descriptions and proposed names of species and the deposition of specimens. Virus taxonomy is developed through a different system of annual submission of formal taxonomy proposals (TPs) that can be submitted by anyone but are typically prepared by a study group appointed by the International Committee on Taxonomy of Viruses (ICTV) and consisting of experts on a particular group of viruses. These are initially evaluated by an expert subcommittee and by the executive committee (EC) of the ICTV. EC-approved TPs are then submitted for evaluation and a ratification vote by the wider ICTV membership. Following ratification, the new taxonomy is annually updated in the Master Species List, associated databases and bioinformatic resources. The process is consistent, creates traceability in assignments and supports a fully evaluated, hierarchical classification and nomenclature of all taxonomic ranks from species to realms. The structure also facilitates large-scale and coordinated changes to virus taxonomy, such as the recent introduction of a binomial species nomenclature.
TPs are available on the ICTV website after ratification, but they are not indexed in bibliographic databases and are not easily cited. Authors of TPs do not receive citation credit for adopted proposals, and their voluntary contributions are largely invisible in the published literature. For greater visibility of TPs and their authors, the ICTV will commence the annual publication of summaries of all TPs from each ICTV subcommittee. These summaries will provide a searchable compendium of all annual taxonomy changes and additions as well as direct links to the Master Species List and other ICTV bioinformatic resources. Their publication will provide due credit and citations for their authors, form the basis for disseminating taxonomy decisions and promote greater visibility and accessibility to taxonomy changes for the virology community. en-copyright= kn-copyright= en-aut-name=MayneRichard en-aut-sei=Mayne en-aut-mei=Richard kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SimmondsPeter en-aut-sei=Simmonds en-aut-mei=Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SmithDonald B. en-aut-sei=Smith en-aut-mei=Donald B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AdriaenssensEvelien M. en-aut-sei=Adriaenssens en-aut-mei=Evelien M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LefkowitzElliot J. en-aut-sei=Lefkowitz en-aut-mei=Elliot J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OksanenHanna M. en-aut-sei=Oksanen en-aut-mei=Hanna M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZerbiniFrancisco Murilo en-aut-sei=Zerbini en-aut-mei=Francisco Murilo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Alfenas-ZerbiniPoliane en-aut-sei=Alfenas-Zerbini en-aut-mei=Poliane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AylwardFrank O en-aut-sei=Aylward en-aut-mei=Frank O kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Freitas-AstúaJuliana en-aut-sei=Freitas-Astúa en-aut-mei=Juliana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HendricksonR. Curtis en-aut-sei=Hendrickson en-aut-mei=R. Curtis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HughesHolly R. en-aut-sei=Hughes en-aut-mei=Holly R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KrupovicMart en-aut-sei=Krupovic en-aut-mei=Mart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KuhnJens H. en-aut-sei=Kuhn en-aut-mei=Jens H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ŁobockaMałgorzata en-aut-sei=Łobocka en-aut-mei=Małgorzata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MushegianArcady R. en-aut-sei=Mushegian en-aut-mei=Arcady R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=PenzesJudit en-aut-sei=Penzes en-aut-mei=Judit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MuñozAlejandro Reyes en-aut-sei=Muñoz en-aut-mei=Alejandro Reyes kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=RobertsonDavid L. en-aut-sei=Robertson en-aut-mei=David L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=RouxSimon en-aut-sei=Roux en-aut-mei=Simon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=RubinoLuisa en-aut-sei=Rubino en-aut-mei=Luisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=SabanadzovicSead en-aut-sei=Sabanadzovic en-aut-mei=Sead kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TurnerDann en-aut-sei=Turner en-aut-mei=Dann kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=Van DoorslaerKoenraad en-aut-sei=Van Doorslaer en-aut-mei=Koenraad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=VarsaniArvind en-aut-sei=Varsani en-aut-mei=Arvind kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Nuffield Department of Medicine, University of Oxford kn-affil= affil-num=2 en-affil=Nuffield Department of Medicine, University of Oxford kn-affil= affil-num=3 en-affil=Nuffield Department of Medicine, University of Oxford kn-affil= affil-num=4 en-affil=Quadram Institute Bioscience kn-affil= affil-num=5 en-affil=Department of Microbiology, University of Alabama at Birmingham kn-affil= affil-num=6 en-affil=Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki kn-affil= affil-num=7 en-affil=Departamento de Fitopatologia/BIOAGRO, Universidade Federal de Viçosa kn-affil= affil-num=8 en-affil=Departamento de Microbiologia, Universidade Federal de Viçosa kn-affil= affil-num=9 en-affil=Department of Biological Sciences, Virginia Tech kn-affil= affil-num=10 en-affil=Embrapa Cassava and Fruits, Cruz das Almas kn-affil= affil-num=11 en-affil=Department of Microbiology, University of Alabama at Birmingham kn-affil= affil-num=12 en-affil=Centers for Disease Control and Prevention kn-affil= affil-num=13 en-affil=Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit kn-affil= affil-num=14 en-affil=Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health kn-affil= affil-num=15 en-affil=Institute of Biochemistry and Biophysics of the Polish Academy of Sciences kn-affil= affil-num=16 en-affil=Division of Molecular and Cellular Biosciences, National Science Foundation kn-affil= affil-num=17 en-affil=Institute for Quantitative Biomedicine, Rutgers University kn-affil= affil-num=18 en-affil=Departamento de Ciencias Biológicas, Universidad de los Andes kn-affil= affil-num=19 en-affil=MRC-University of Glasgow Centre for Virus Research kn-affil= affil-num=20 en-affil=Department of Energy, Joint Genome Institute, Lawrence Berkeley National Laboratory kn-affil= affil-num=21 en-affil=Consiglio Nazionale delle Ricerche, Istituto per la Protezione Sostenibile delle Piante, Sede Secondaria di Bari kn-affil= affil-num=22 en-affil=Department of Agricultural Science and Plant Protection, Mississippi State University kn-affil= affil-num=23 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=24 en-affil=Molecular Biology, University of the West of England kn-affil= affil-num=25 en-affil=Department of Immunobiology, School of Animal and Comparative Biomedical Sciences, BIO5 Institute, University of Arizona Cancer Center kn-affil= affil-num=26 en-affil=The Biodesign Center for Fundamental and Applied Microbiomics, School of Life Sciences, Center for Evolution and Medicine, Arizona State University kn-affil= en-keyword=ICTV kn-keyword=ICTV en-keyword=master species list kn-keyword=master species list en-keyword=taxonomy proposal kn-keyword=taxonomy proposal en-keyword=virus taxonomy kn-keyword=virus taxonomy END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e06572 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Viral RNA Silencing Suppressor Modulates Reactive Oxygen Species Levels to Induce the Autophagic Degradation of Dicer‐Like and Argonaute‐Like Proteins en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mounting evidence indicates that viruses exploit elevated reactive oxygen species (ROS) levels to promote replication and pathogenesis, yet the mechanistic underpinnings of this viral strategy remain elusive for many viral systems. This study uncovers a sophisticated viral counter-defense mechanism in the Cryphonectria hypovirus 1 (CHV1)-Fusarium graminearum system, where the viral p29 protein subverts host redox homeostasis to overcome antiviral responses. That p29 directly interacts with and inhibits the enzymatic activity of fungal NAD(P)H-dependent FMN reductase 1 (FMR1), leading to increased ROS accumulation and subsequent autophagy activation is demonstrated. Strikingly, this ROS-induced autophagy selectively targets for degradation two core antiviral RNA silencing components against CHV1 in F. graminearum, Dicer-like 2 (DCL2) and Argonaute-like 1 (AGL1), thereby compromising the host's primary antiviral defense system. Genetic analysis confirms this coordinated hijacking of host machineries, as CHV1 shows enhanced accumulation in the FMR1 knockout and reduced accumulation in autophagy-deficient fungal strains. This work reveals a tripartite interplay among oxidative stress, autophagy, and RNA silencing that CHV1 manipulates through p29 multifunctional activity. These findings provide a model for how viruses coordinately regulate distinct host defense systems to optimize infection. en-copyright= kn-copyright= en-aut-name=ZhaiShiyu en-aut-sei=Zhai en-aut-mei=Shiyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PangTianxing en-aut-sei=Pang en-aut-mei=Tianxing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PengShiyu en-aut-sei=Peng en-aut-mei=Shiyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZouShenshen en-aut-sei=Zou en-aut-mei=Shenshen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DengZhiping en-aut-sei=Deng en-aut-mei=Zhiping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KangZhensheng en-aut-sei=Kang en-aut-mei=Zhensheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AndikaIda Bagus en-aut-sei=Andika en-aut-mei=Ida Bagus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SunLiying en-aut-sei=Sun en-aut-mei=Liying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= affil-num=2 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= affil-num=3 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= affil-num=4 en-affil=Department of Plant Pathology, College of Plant Protection, Shandong Agricultural University kn-affil= affil-num=5 en-affil=Institute of Virology and Biotechnology, Zhejiang Academy of Agricultural Sciences kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=7 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= affil-num=8 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= affil-num=9 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= en-keyword=argonaute kn-keyword=argonaute en-keyword=autophagic degradation kn-keyword=autophagic degradation en-keyword=cryphonectria hypovirus 1 kn-keyword=cryphonectria hypovirus 1 en-keyword=dicer kn-keyword=dicer en-keyword=reactive oxygen species kn-keyword=reactive oxygen species en-keyword=RNA silencing suppressor kn-keyword=RNA silencing suppressor END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue= article-no= start-page=101081 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=AHA’s Life’s Essential-8 cardiovascular health metrics and progression of coronary artery calcification in Japanese men en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and aims: The American Heart Association’s Life’s Essential-8 (LE8) cardiovascular health (CVH) metrics is considered a comprehensive framework for optimal cardiovascular wellbeing. However, its relationship with the progression of subclinical atherosclerosis, like coronary artery calcification (CAC), is not clarified. We investigated the associations of LE8 CVH metrics with the prevalence and progression of CAC in Japanese men.
Methods: We analyzed data from 760 asymptomatic men participating in the Shiga Epidemiological Study of Subclinical Atherosclerosis. We assessed baseline (2006–2008) LE8 CVH (low, 0–49 points; moderate, 50–79 points; high, 80–100 points) using its eight components (diet, physical activity assessed by step count, smoking, sleep, body mass index, blood lipids, blood glucose, blood pressure). We quantified CAC at baseline and follow-up of 5 years employing Agatston’s method and defined its baseline prevalence (CAC >0) and progression (employing Berry’s criteria). Modified Poisson regression analyses were used to estimate risk ratio (RR) and 95 % confidence interval (CI), adjusted for age and family history of cardiovascular disease.
Results: Participants (mean [SD] age, 63.8 [9.4] years) had 63.2 % and 44.9 % prevalence of CAC at baseline and CAC progression at follow-up, respectively. Individuals with moderate and low CVH at baseline had a higher risk of prevalent CAC (RR [95 % CI], 1.42 [1.18–1.71] and 2.07 [1.67–2.57], respectively) at baseline, compared to those with high CVH. Those with moderate and low CVH at baseline had a higher risk of CAC progression (RR [95 % CI], 1.52 [1.17–1.97] and 1.99 [1.42–2.81], respectively), compared to high CVH individuals.
Conclusions: A lower LE8 CVH is significantly associated with a higher risk of prevalence and progression of CAC in general Japanese men. en-copyright= kn-copyright= en-aut-name=MondalRajib en-aut-sei=Mondal en-aut-mei=Rajib kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KadotaAya en-aut-sei=Kadota en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanoYuichiro en-aut-sei=Yano en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KadowakiSayaka en-aut-sei=Kadowaki en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToriiSayuki en-aut-sei=Torii en-aut-mei=Sayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KondoKeiko en-aut-sei=Kondo en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaradaAkiko en-aut-sei=Harada en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawashimaMegumi en-aut-sei=Kawashima en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyazawaItsuko en-aut-sei=Miyazawa en-aut-mei=Itsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SegawaHiroyoshi en-aut-sei=Segawa en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WatanabeYoshiyuki en-aut-sei=Watanabe en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakagawaYoshihisa en-aut-sei=Nakagawa en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiyoshiAkira en-aut-sei=Fujiyoshi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MiuraKatsuyuki en-aut-sei=Miura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=2 en-affil=Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=3 en-affil=Department of General Medicine, Faculty of Medicine, Juntendo University kn-affil= affil-num=4 en-affil=Department of Public Health, Shiga University of Medical Science kn-affil= affil-num=5 en-affil=Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=6 en-affil=Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=7 en-affil=Department of Medical Statistics, NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=8 en-affil=Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=9 en-affil=Department of Internal Medicine, Shiga University of Medical Science kn-affil= affil-num=10 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=11 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= affil-num=14 en-affil=Department of Hygiene, School of Medicine, Okayama Medical University kn-affil= affil-num=15 en-affil=Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= en-keyword=Life’s essential-8 kn-keyword=Life’s essential-8 en-keyword=Cardiovascular health metrics kn-keyword=Cardiovascular health metrics en-keyword=Subclinical atherosclerosis kn-keyword=Subclinical atherosclerosis en-keyword=Coronary artery calcification kn-keyword=Coronary artery calcification en-keyword=CAC progression kn-keyword=CAC progression END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=9916 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A node-localized efflux transporter for loading iron to developing tissues in rice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Iron (Fe) is an essential micronutrient for plant growth and development. It plays crucial roles in various organs and tissues of plants, but the molecular mechanisms governing its distribution to the above-ground parts after root uptake remain unclear. In this study, we identify OsIET1 (Oryza sativa Iron Efflux Transporter 1), a rice gene highly expressed in the nodes. OsIET1 encodes a plasma membrane-localized protein, which shows efflux transport activity for ferrous iron. It is predominantly expressed in the xylem regions of diffuse vascular bundles, and its expression is upregulated under high Fe conditions. Disruption of OsIET1 impairs Fe allocation, reducing Fe transport to developing tissues (young leaves and grains), while increasing accumulation in nodes and older leaves. This misdistribution causes chlorosis in young leaves and decreases grain yield, especially under Fe-deficient conditions. Furthermore, we detect excessive Fe deposition around the xylem of diffuse vascular bundles in the nodes. Given the pivotal role of nodes in mineral distribution, our results indicate that OsIET1 mediates inter-vascular Fe transfer by facilitating Fe loading into the xylem of diffuse vascular bundles. This process ensures preferential Fe delivery to developing tissues, thereby promoting optimal plant growth and productivity. en-copyright= kn-copyright= en-aut-name=CheJing en-aut-sei=Che en-aut-mei=Jing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HuangSheng en-aut-sei=Huang en-aut-mei=Sheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=QuYuting en-aut-sei=Qu en-aut-mei=Yuting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshiokaYuma en-aut-sei=Yoshioka en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TomitaChiyuri en-aut-sei=Tomita en-aut-mei=Chiyuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyajiTakaaki en-aut-sei=Miyaji en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LiuZhenyang en-aut-sei=Liu en-aut-mei=Zhenyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShenRenfang en-aut-sei=Shen en-aut-mei=Renfang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamajiNaoki en-aut-sei=Yamaji en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MaJian Feng en-aut-sei=Ma en-aut-mei=Jian Feng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences kn-affil= affil-num=8 en-affil=State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences kn-affil= affil-num=9 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=10 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=27 article-no= start-page=6557 end-page=6563 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fluorescence detection of DNA with a single-base mismatch by a Tm-independent peptide nucleic acid (PNA) twin probe en-subtitle= kn-subtitle= en-abstract= kn-abstract=There is a need to develop efficient methods for detecting target nucleic acids to enable the rapid diagnosis and early treatment of diseases. We previously demonstrated that a peptide nucleic acid (PNA) twin probe, consisting of two PNAs each containing a fluorescent dye, with pyrene at one end, detects target DNA sequence-specifically through pyrene excimer emission. In this study, to advance the development of this probe system, we further investigated the fluorescence properties of the PNA twin probe P1 and P2, and found that the excimer fluorescence was significantly reduced when a mismatched base in the DNA sequence was present at the site of P1 closest to the pyrene. In other words, this probe was found to detect single-base mismatches without taking into account the thermal stability of the PNA/DNA hybrid. The detection limit of this PNA twin probe for the single-base-mismatched DNA was 2.7 nM. In the future, this probe should lead to a method to detect point mutations in endogenous nucleic acids within cells. en-copyright= kn-copyright= en-aut-name=IshiiKoki en-aut-sei=Ishii en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShigetoHajime en-aut-sei=Shigeto en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamuraShohei en-aut-sei=Yamamura en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImaiYoshitane en-aut-sei=Imai en-aut-mei=Yoshitane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitamatsuMizuki en-aut-sei=Kitamatsu en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Applied Chemistry, Kindai University kn-affil= affil-num=2 en-affil=Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=3 en-affil=Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=4 en-affil=Department of Applied Chemistry, Kindai University kn-affil= affil-num=5 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Applied Chemistry, Kindai University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=478 cd-vols= no-issue= article-no= start-page=123708 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Two Japanese families with adult-onset leukoencephalopathy caused by pathogenic variants in CST3 en-subtitle= kn-subtitle= en-abstract= kn-abstract=CST3 (NM_000099.4) encodes cystatin C, whose C-terminal truncating variants in this gene have recently been reported to cause adult-onset leukoencephalopathy, characterized by headaches, transient neurological symptoms, and distinct imaging findings. We present four patients from two Japanese families, including one with a novel variant (c.358-2_395del). Three patients from one family developed chronic headaches around the age of 20, whereas the patient from the other family remained asymptomatic until his fifties. mRNA analysis of the patient with c.358-2_395del revealed a splicing alteration leading to an in-frame deletion (p.Lys120_Gln133del), representing the first CST3 variant that does not result in a truncated protein. These findings broaden our understanding of the clinical and genetic spectra of CST3-related leukoencephalopathy (114 words). en-copyright= kn-copyright= en-aut-name=OrimoKenta en-aut-sei=Orimo en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShiomiKazutaka en-aut-sei=Shiomi en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotoRyoji en-aut-sei=Goto en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuromiYumiko en-aut-sei=Kuromi en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsudaNozomu en-aut-sei=Matsuda en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanaiKazuaki en-aut-sei=Kanai en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurokawaRyo en-aut-sei=Kurokawa en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NomotoJunko en-aut-sei=Nomoto en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TanakaMasaki en-aut-sei=Tanaka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OmaeYosuke en-aut-sei=Omae en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KawaiYosuke en-aut-sei=Kawai en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TokunagaKatsushi en-aut-sei=Tokunaga en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Department of Neurology, Fukushima Medical University kn-affil= affil-num=7 en-affil=Department of Neurology, Fukushima Medical University kn-affil= affil-num=8 en-affil=Department of Neurology, Fukushima Medical University kn-affil= affil-num=9 en-affil=Department of Radiology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=12 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=13 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=14 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine kn-affil= affil-num=15 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine kn-affil= affil-num=16 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine kn-affil= affil-num=17 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=18 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=CST3 kn-keyword=CST3 en-keyword=Cystatin-C kn-keyword=Cystatin-C en-keyword=Leukodystrophy kn-keyword=Leukodystrophy en-keyword=Leukoencephalopathy kn-keyword=Leukoencephalopathy en-keyword=Middle cerebellar peduncle kn-keyword=Middle cerebellar peduncle en-keyword=MCP kn-keyword=MCP END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=4 article-no= start-page=dsaf016 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250619 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Reference-based chromosome-scale assembly of Japanese barley (Hordeum vulgare ssp. vulgare) cultivar Hayakiso 2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Current advances in next-generation sequencing (NGS) technology and assembling programs permit construct chromosome-level genome assemblies in various plants. In contrast to resequencing, the genome sequences provide comprehensive annotation data useful for plant genetics and breeding. Herein, we constructed a reference-based genome assembly of winter barley (H. vulgare ssp. vulgare) cv. ‘Hayakiso 2’ using long and short read NGS data and barley reference genome sequences from ‘Morex’. We constructed ‘Hayakiso 2’ genome sequences covering 4.3 Gbp with 55,477 genes. Comparative genomics revealed that 14,106 genes had orthologs to two barley data, wheat (A, B, and D homoeologs, respectively), and rice. From the gene ontology analysis, 2,494 orthologs against wheat and rice but not two barley contained agricultural important genes, such as ‘response to biotic and abiotic stress’ and ‘metabolic process’. Phylogenetic analysis using 76 pangenome data indicated that ‘Hayakiso 2’ was clustered into Japanese-type genomes with unique alleles. ‘Hayakiso 2’ genome sequences showed known genes related to flowering and facilitated barley breeding through the development of various markers related to agronomically important alleles such as tolerance to various types of biotic and abiotic stress. Therefore, ‘Hayakiso 2’ genome sequences will be used for the further barley breeding. en-copyright= kn-copyright= en-aut-name=TanakaTsuyoshi en-aut-sei=Tanaka en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaraguchiYuhi en-aut-sei=Haraguchi en-aut-mei=Yuhi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TodorokiTakatomo en-aut-sei=Todoroki en-aut-mei=Takatomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaishoDaisuke en-aut-sei=Saisho en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AbikoTomomi en-aut-sei=Abiko en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KaiHiroomi en-aut-sei=Kai en-aut-mei=Hiroomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Bioinformatics Unit, Research Center for Advanced Analysis, National Agriculture and Food Research Organization kn-affil= affil-num=2 en-affil=Department of Crop Production and Breeding, Fukuoka Agriculture and Forestry Research Center kn-affil= affil-num=3 en-affil=Department of Crop Production and Breeding, Fukuoka Agriculture and Forestry Research Center kn-affil= affil-num=4 en-affil=Barley Germplasm Center, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Laboratory of Agroecology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University kn-affil= affil-num=6 en-affil=Department of Crop Production and Breeding, Fukuoka Agriculture and Forestry Research Center kn-affil= en-keyword=Hordeum vulgare kn-keyword=Hordeum vulgare en-keyword=genome sequencing kn-keyword=genome sequencing en-keyword=long-read sequencing kn-keyword=long-read sequencing END start-ver=1.4 cd-journal=joma no-vol=89 cd-vols= no-issue=11 article-no= start-page=337 end-page=343 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ti-18Nb-xAl合金の構成相と材料特性に及ぼすAl添加量の影響 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The Ti-18mass%Nb alloy with a quenched α” martensitic structure exhibited a high damping capacity. However, there are issues such as lower strength than annealed α+β structure and decreasing damping capacity due to heating until 400 K. Therefore, in this study, to address these issues, we investigated the effect of Al addition on the constituent phases and material properties of Ti-18Nb-xAl alloys. The crystal structure was determined by examining the lattice constant and unit volume using X-ray diffraction, and optical microscopy was also performed. The material properties were investigated by Vickers hardness, Young’s modulus, internal friction, tensile tests, and DSC measurements. Vickers hardness and tensile strength increased with increasing Al content. This is thought to be due to the combined effects of the refinement of the microstructure and solid-solution strengthening due to Al addition. The Young’s modulus increased slightly from 0Al to 1Al, but increased significantly to 4Al. Internal friction was highest for 0Al and decreased for 4Al, whereas 7Al showed a higher value than 1Al. In the DSC heating curves, there was a decrease in the exothermic peak starting temperature and an increase in the phase-transformation heat with the addition of Al, except for 1Al. It was suggested that these changes in Ti-18Nb-xAl alloys were influenced by the structure of the quenched α” phase, texture, and pseudoelasticity or phase transformation by deformation. en-copyright= kn-copyright= en-aut-name=MantaniYoshikazu en-aut-sei=Mantani en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakemotoYoshito en-aut-sei=Takemoto en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Materials Science and Engineering, National Institute of Technology (KOSEN), Suzuka College kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=ternary titanium alloy kn-keyword=ternary titanium alloy en-keyword=martensite kn-keyword=martensite en-keyword=lattice constant kn-keyword=lattice constant en-keyword=hardness kn-keyword=hardness en-keyword=Young’s modulus kn-keyword=Young’s modulus en-keyword=internal friction kn-keyword=internal friction en-keyword=cyclic tensile test kn-keyword=cyclic tensile test en-keyword=texture kn-keyword=texture END start-ver=1.4 cd-journal=joma no-vol=108 cd-vols= no-issue= article-no= start-page=104508 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Introduction to the “Japanese and Western approaches to psychotrauma” symposium en-subtitle= kn-subtitle= en-abstract= kn-abstract=Understandings of psychotrauma have changed throughout medical history, shaped by cultural and social factors. Reviewing transcultural perspectives of psychotrauma helps understand its complexities and contextual impacts. This paper summarizes the Japan–Netherlands symposium on psychotrauma held on March 1, 2024. Despite experiencing psychological trauma from World War II and numerous natural disasters, Japan did not actively research post-traumatic stress disorder (PTSD) for nearly 50 years after the war. The Great Hanshin-Awaji Earthquake and the Tokyo subway Sarin gas attack (1995) popularized the term PTSD in Japan and triggered related research. The absence of psychotrauma research in Japan may reflect a form of state-level PTSD, characterized by avoidance. Japan’s collectivist culture, stigma against seeking psychological help, view of patience as a virtue, survivor guilt, and moral injury were potential related factors. Additionally, sociocultural factors (e.g., insufficient collective grieving and focusing on post-war reconstruction) were discussed as potential hinderances to discussing war experiences. From a European perspective, we examined how “Konzentrationslager” (KZ) syndrome, a trauma-related disorder, evolved independently into diverse conceptual frameworks, ultimately contributing to the acceptance of PTSD following its introduction in 1980. Beyond state compensation for concentration camp survivors, advocacy by feminist movements and veterans' groups increased awareness of psychotrauma across Europe, fostering scholarly research and public discourse. Both PTSD and KZ syndromes are diagnostic categories shaped by specific historical and cultural contexts and should not be regarded as simple, universally applicable medical conditions. They reflect how trauma is interpreted and responded to differently depending on cultural, political, and historical factors. en-copyright= kn-copyright= en-aut-name=NagamineMasanori en-aut-sei=Nagamine en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaoTomoyo en-aut-sei=Nakao en-aut-mei=Tomoyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=van BergenLeo en-aut-sei=van Bergen en-aut-mei=Leo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShigemuraJun en-aut-sei=Shigemura en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoTaku en-aut-sei=Saito en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=van der DoesFlorentine H.S. en-aut-sei=van der Does en-aut-mei=Florentine H.S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KitanoMasato en-aut-sei=Kitano en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=GiltayErik J. en-aut-sei=Giltay en-aut-mei=Erik J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=van der WeeNic J. en-aut-sei=van der Wee en-aut-mei=Nic J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=VermettenEric en-aut-sei=Vermetten en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Behavioral Science, National Defense Medical College Research Institute kn-affil= affil-num=2 en-affil=Graduate School of Humanities and Social Sciences, Okayama University kn-affil= affil-num=3 en-affil=Freelance Medical Historian kn-affil= affil-num=4 en-affil=Faculty of Health Sciences, Mejiro University kn-affil= affil-num=5 en-affil=Division of Behavioral Science, National Defense Medical College Research Institute kn-affil= affil-num=6 en-affil=Department of Psychiatry, Leiden University Medical Center (LUMC) kn-affil= affil-num=7 en-affil=Division of Behavioral Science, National Defense Medical College Research Institute kn-affil= affil-num=8 en-affil=Department of Psychiatry, Leiden University Medical Center (LUMC) kn-affil= affil-num=9 en-affil=Department of Psychiatry, Leiden University Medical Center (LUMC) kn-affil= affil-num=10 en-affil=Department of Psychiatry, Leiden University Medical Center (LUMC) kn-affil= en-keyword=Psychotrauma kn-keyword=Psychotrauma en-keyword=World War II kn-keyword=World War II en-keyword=Japan kn-keyword=Japan en-keyword=Europe kn-keyword=Europe en-keyword=KZ syndrome kn-keyword=KZ syndrome en-keyword=Post-traumatic stress disorder kn-keyword=Post-traumatic stress disorder END start-ver=1.4 cd-journal=joma no-vol=34 cd-vols= no-issue=1 article-no= start-page=46 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251009 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Highly efficient transgenesis mediated by Tip100 transposon system in medaka en-subtitle= kn-subtitle= en-abstract= kn-abstract=Transgenesis mediated by transposon is an effective approach for introducing exogenous DNA into the nuclear genome and establishing stable transgenic strains that efficiently express genetic tools. Although the DNA transposon Tol2 is widely used for transgenesis in zebrafish, its endogenous transpositional activity can lead to unintended transgene mobilization, making it unsuitable for transgenesis in medaka (Oryzias latipes). Here, we demonstrated that the DNA transposon Tip100, originally identified in the common morning glory (Ipomoea purpurea), an ornamental plant, can serve as a useful tool for transgenesis in Japanese medaka. The GFP transgene cassette, when co-injected with Tip100 transposase mRNA, was expressed in significantly higher number of somatic cells in the injected fish. Furthermore, a transgene flanked by truncated recognition sequences (100 bp each) exhibited expression levels comparable to those of the original vector containing the full 2.2 kb recognition sequence. Injection of a transgene driven by a germline-specific promoter revealed that fish injected with Tip100 mRNA exhibited a significantly higher germline transmission rate (42/68; 62.7%) compared to those injected without the mRNA (13/62; 21.0%). We successfully established transgenic strains by outcrossing injected founders with GFP-positive germ cells (7/7; 100%) and demonstrated that the transgenes were randomly integrated into the medaka genome, generating 8-bp duplications at the insertional sites–an insertional signature of the hAT superfamily of transposons. Our findings indicate that the Tip100 system is a promising tool for generating stable transgenic strains that express various genetic tools in medaka and potentially other fish species. en-copyright= kn-copyright= en-aut-name=TanakaYoshitaka en-aut-sei=Tanaka en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SekiTakahide en-aut-sei=Seki en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HoshinoAtsushi en-aut-sei=Hoshino en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AnsaiSatoshi en-aut-sei=Ansai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Ushimado Marine Institute (UMI), Okayama University kn-affil= affil-num=2 en-affil=Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=3 en-affil=National Institute for Basic Biology kn-affil= affil-num=4 en-affil=Ushimado Marine Institute (UMI), Okayama University kn-affil= en-keyword=Fish kn-keyword=Fish en-keyword=Medaka kn-keyword=Medaka en-keyword=Morning glory kn-keyword=Morning glory en-keyword=Transgenic kn-keyword=Transgenic en-keyword=Transposon kn-keyword=Transposon END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=5 article-no= start-page=3933 end-page=3946 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Topology-Driven Configuration of Emulation Networks With Deterministic Templating en-subtitle= kn-subtitle= en-abstract= kn-abstract=Network emulation is an important component of a digital twin for verifying network behavior without impacting on the service systems. Although we need to repeatedly change network topologies and configuration settings as a part of trial and error for verification, it is not easy to reflect the change without failures because the change affects multiple devices, even if it is as simple as adding a device. We present topology-driven configuration, an idea to separate network topology and generalized configuration to make it easy to change them. Based on this idea, we aim to realize a scalable, simple, and effective configuration platform for emulation networks. We design a configuration generation method using simple and deterministic config templates with a new network parameter data model, and implement it as dot2net. We evaluate three perspectives, scalability, simplicity, and efficacy, of the proposed method using dot2net through measurement and user experiments on existing test network scenarios. en-copyright= kn-copyright= en-aut-name=KobayashiSatoru en-aut-sei=Kobayashi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShiibaRyusei en-aut-sei=Shiiba en-aut-mei=Ryusei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiwaShinsuke en-aut-sei=Miwa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyachiToshiyuki en-aut-sei=Miyachi en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukudaKensuke en-aut-sei=Fukuda en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Informatics, School of Multidisciplinary Sciences, The Graduate University of Advanced Studies, Sokendai kn-affil= affil-num=3 en-affil=StarBED Technology Center, Testbed Research, Development and Operations Laboratory, National Institute of Information and Communications Technology kn-affil= affil-num=4 en-affil=Strategic Planning Department, Strategic Planning Office, National Institute of Information and Communications Technology kn-affil= affil-num=5 en-affil=Department of Informatics, School of Multidisciplinary Sciences, The Graduate University of Advanced Studies, Sokendai kn-affil= en-keyword=Configuration management kn-keyword=Configuration management en-keyword=template kn-keyword=template en-keyword=emulation network kn-keyword=emulation network en-keyword=topology graph kn-keyword=topology graph END start-ver=1.4 cd-journal=joma no-vol=135 cd-vols= no-issue=7 article-no= start-page=1329 end-page=1343 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250417 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Molecular polymorphisms of the nuclear and chloroplast genomes among African melon germplasms reveal abundant and unique genetic diversity, especially in Sudan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aims Africa is rich in wild species of Cucumis and is considered one of the places of origin of melon. However, our knowledge of African melon is limited, and genetic studies using melon germplasms with wide geographical coverage are required. Here, we analysed the genetic structure of African melons, with emphasis on Sudan.
Methods Ninety-seven accessions of African melon were examined along with 77 reference accessions representing Asian melon and major horticultural groups. Molecular polymorphisms in the nuclear and chloroplast genomes were investigated using 12 RAPD, 7 SSR and 3 SNP markers. Horticultural traits, including seed size, were measured for 46 accessions, mainly from Sudan.
Key Results African melons were divided into large and small seed-types based on seed length: large seed-type from Northern Africa and small seed-type from Western and Southern Africa. Both seed types are common in Sudan. Molecular genetic diversity in these geographical populations was as high as in India, the Asian centre of melon domestication. Large seed-types from Northern Africa were assigned to Pop4 by structure analysis and had Ib cytoplasm in common with Cantalupensis, Inodorus and Flexuosus. Small seed-types were highly diversified and geographically differentiated; specifically, Pop1 with Ia cytoplasm in Southern Africa and South Asia, Pop2 with Ia in East Asia, including Conomon and Makuwa, and Pop3 with Ia or Ic in Africa. Sudanese small seed-types were grouped in Pop3, while their cytoplasm type was a mixture of Ia and Ic. Sudanese Tibish had Ic cytoplasm, which was unique in Africa, common in Western Africa and Sudan, and also found in wild or feral types.
Conclusions Melon of Ic lineage, including Tibish, originated from wild melon in the ‘western Sudan region’, and independently of melon with Ia or Ib cytoplasm, which originated in Asia. This clearly indicates the polyphyletic origin of melon. en-copyright= kn-copyright= en-aut-name=ImohOdirichi Nnennaya en-aut-sei=Imoh en-aut-mei=Odirichi Nnennaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShigitaGentaro en-aut-sei=Shigita en-aut-mei=Gentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugiyamaMitsuhiro en-aut-sei=Sugiyama en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DungTran Phuong en-aut-sei=Dung en-aut-mei=Tran Phuong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaKatsunori en-aut-sei=Tanaka en-aut-mei=Katsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakahashiMami en-aut-sei=Takahashi en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishimuraKazusa en-aut-sei=Nishimura en-aut-mei=Kazusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MondenYuki en-aut-sei=Monden en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishidaHidetaka en-aut-sei=Nishida en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GodaMashaer en-aut-sei=Goda en-aut-mei=Mashaer kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=PitratMichel en-aut-sei=Pitrat en-aut-mei=Michel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KatoKenji en-aut-sei=Kato en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Institute of Vegetable and Floriculture Science, National Agriculture and Food Research Organization (NARO) kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Agriculture and Life Science, Hirosaki University kn-affil= affil-num=6 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Plant Genetic Resources Conservation and Research Center, Agricultural Research Corporation kn-affil= affil-num=11 en-affil=INRAE, UR1052, Génétique et amélioration des fruits et légumes kn-affil= affil-num=12 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Cucumis melo kn-keyword=Cucumis melo en-keyword=Africa kn-keyword=Africa en-keyword=chloroplast genome kn-keyword=chloroplast genome en-keyword=domestication kn-keyword=domestication en-keyword=genetic diversity kn-keyword=genetic diversity en-keyword=genetic resources kn-keyword=genetic resources en-keyword=maternal lineage kn-keyword=maternal lineage en-keyword=melon kn-keyword=melon en-keyword=phylogeny kn-keyword=phylogeny en-keyword=polyphyletic origin kn-keyword=polyphyletic origin en-keyword=seed size kn-keyword=seed size en-keyword=Tibish kn-keyword=Tibish END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=10 article-no= start-page=1623 end-page=1625 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251006 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The OsATG8–OsATG1–SPIN6 module: Linking nutrient sensing to OsRac1-mediated rice immunity via autophagy-independent mechanisms en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KouYanjun en-aut-sei=Kou en-aut-mei=Yanjun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawanoYoji en-aut-sei=Kawano en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=State Key Laboratory of Rice Biology and Breeding, China National Rice Research Institute kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=8226 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Persistent homology elucidates hierarchical structures responsible for mechanical properties in covalent amorphous solids en-subtitle= kn-subtitle= en-abstract= kn-abstract=Understanding how atomic-level structures govern the mechanical properties of amorphous materials remains a fundamental challenge in solid-state physics. Under mechanical loading, amorphous materials exhibit simple affine and spatially inhomogeneous nonaffine displacements that contribute to the elastic modulus through the Born (affine) and nonaffine terms, respectively. The differences between soft local structures characterized by small Born terms or large nonaffine displacements have yet to be elucidated. This challenge is particularly complex in covalent amorphous materials such as silicon, where the medium-range order (MRO) plays a crucial role in the network structure. To address these issues, we combined molecular dynamics simulations with persistent homology analysis. Our results reveal that local structures with small Born terms are governed by short-range characteristics, whereas those with large nonaffine displacements exhibit hierarchical structures in which short-range disorder is embedded within the MRO. These hierarchical structures are also strongly correlated with low-energy localized vibrational excitations. Our findings demonstrate that the mechanical responses and dynamic properties of covalent amorphous materials are intrinsically linked to the MRO, providing a framework for understanding and tailoring their properties. en-copyright= kn-copyright= en-aut-name=MinamitaniEmi en-aut-sei=Minamitani en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraTakenobu en-aut-sei=Nakamura en-aut-mei=Takenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ObayashiIppei en-aut-sei=Obayashi en-aut-mei=Ippei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MizunoHideyuki en-aut-sei=Mizuno en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=SANKEN, The University of Osaka kn-affil= affil-num=2 en-affil=Department of Materials and Chemistry Materials DX Research Center, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=3 en-affil=Center for Artificial Intelligence and Mathematical Data Science, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Arts and Sciences, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=38 article-no= start-page=eadv9952 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250919 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Polymeric microwave rectifiers enabled by monolayer-thick ionized donors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Solution processing of polymeric semiconductors provides a facile way to fabricate functional diodes. However, energy barriers at metal-semiconductor interfaces often limit their performance. Here, we report rectifying polymer diodes with markedly modified energy-level alignments. The gold electrode surface was treated with a dimeric metal complex, which resulted in a shallow work function of 3.7 eV by forming a monolayer-thick ionized donor layer. When a polymeric semiconductor was coated on the treated electrode, most of the ionized donors remained at the metal-semiconductor interface. The confined ionized donors with the ideal thickness enabled fabrication of a polymer diode with a forward current density of over 100 A cm−2. Furthermore, a power conversion efficiency of 7.9% was observed for rectification at a microwave frequency of 920 MHz, which is orders of magnitude higher than that reported for organic diodes. Our findings will pave a way to solution-processed high-frequency and high-power devices. en-copyright= kn-copyright= en-aut-name=OsakabeNobutaka en-aut-sei=Osakabe en-aut-mei=Nobutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HerJeongeun en-aut-sei=Her en-aut-mei=Jeongeun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanetaTakahiro en-aut-sei=Kaneta en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TajimaAkiko en-aut-sei=Tajima en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LonghiElena en-aut-sei=Longhi en-aut-mei=Elena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TangKan en-aut-sei=Tang en-aut-mei=Kan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujimoriKazuhiro en-aut-sei=Fujimori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BarlowStephen en-aut-sei=Barlow en-aut-mei=Stephen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MarderSeth R. en-aut-sei=Marder en-aut-mei=Seth R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeShun en-aut-sei=Watanabe en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakeyaJun en-aut-sei=Takeya en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamashitaYu en-aut-sei=Yamashita en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=2 en-affil=Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=3 en-affil=Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=4 en-affil=Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=5 en-affil=School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology kn-affil= affil-num=6 en-affil=Renewable and Sustainable Energy Institute, University of Colorado Boulder kn-affil= affil-num=7 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology kn-affil= affil-num=9 en-affil=School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology kn-affil= affil-num=10 en-affil=Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=11 en-affil=Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=12 en-affil=Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=130 cd-vols= no-issue=1 article-no= start-page=e2024JB030704 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Reduced Thermal Conductivity of Hydrous Aluminous Silica and Calcium Ferrite‐Type Phase Promote Water Transportation to Earth's Deep Mantle en-subtitle= kn-subtitle= en-abstract= kn-abstract=Subduction of oceanic slabs introduces chemical heterogeneities in the Earth's interior, which could further induce thermal, seismic, and geodynamical anomalies. Thermal conductivity of slab minerals crucially controls the thermal evolution and dynamics of the subducted slab and ambient mantle, while such an important transport property remains poorly constrained. Here we have precisely measured high pressure-temperature thermal conductivity of hydrous aluminous post-stishovite (ΛHy-Al-pSt) and aluminum-rich calcium ferrite-type phase (ΛCF), two important minerals in the subducted basaltic crust in the lower mantle. Compared to the dry aluminous stishovite and pure stishovite, hydration substantially reduces the ΛHy-Al-pSt, resulting in ∼9.7–13.3 W m−1 K−1 throughout the lower mantle. Surprisingly, the ΛCF remains at ∼3–3.8 W m−1 K−1 in the lower mantle, few-folds lower than previously assumed. Our data modeling offers better constraints on the thermal conductivity of the subducted oceanic crust from mantle transition zone to the lowermost mantle region, which is less thermally conductive than previously modeled. Our findings suggest that if the post-stishovite carries large amounts of water to the lower mantle, the poorer heat conduction through the basaltic crust reduces the slab's temperature, which not only allows the slab bringing more hydrous minerals to greater depth, but also increases slab's density and viscosity, potentially impacting the stability of heterogeneous structures at the lowermost mantle. en-copyright= kn-copyright= en-aut-name=HsiehWen‐Pin en-aut-sei=Hsieh en-aut-mei=Wen‐Pin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DeschampsFrédéric en-aut-sei=Deschamps en-aut-mei=Frédéric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsaoYi‐Chi en-aut-sei=Tsao en-aut-mei=Yi‐Chi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChangJen‐Wei en-aut-sei=Chang en-aut-mei=Jen‐Wei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=CrinitiGiacomo en-aut-sei=Criniti en-aut-mei=Giacomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Institute of Earth Sciences, Academia Sinica kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=Institute of Earth Sciences, Academia Sinica kn-affil= affil-num=4 en-affil=Institute of Earth Sciences, Academia Sinica kn-affil= affil-num=5 en-affil=Institute of Earth Sciences, Academia Sinica kn-affil= affil-num=6 en-affil=Earth and Planets Laboratory, Carnegie Institution for Science kn-affil= en-keyword=thermal conductivity kn-keyword=thermal conductivity en-keyword=post-stishovite kn-keyword=post-stishovite en-keyword=calcium ferrite-type phase kn-keyword=calcium ferrite-type phase en-keyword=basaltic crust kn-keyword=basaltic crust END start-ver=1.4 cd-journal=joma no-vol=40 cd-vols= no-issue=4 article-no= start-page=463 end-page=474 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nationwide diversity of symbolic “city flowers” in Japan is increasing en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recognizing and maintaining locally rooted human–nature interactions is essential for utilizing ecosystem services. Although the general public's awareness of biodiversity and ecosystem services has been examined using various proxies, it remains unclear how local governments—key sectors in creating conservation policies—appreciate them within a solid local context. Here, we focused on the “city flower,” an official symbolic species of Japanese cities, as a new proxy for measuring governmental attitudes toward biota and its services. We aimed to capture temporal changes in the awareness of species with locally relevant value at the city government level by examining the changes in city flowers over more than half a century. Data from the official websites of municipalities, including the names, the adoption years, and the reasons for adoption, revealed two major periods of adoption, with a notable increase in species diversity in and after 1993. This increase could be attributed to a recent reduction in bias toward popular flowers and growing interest in alternative, less popular flowers. Analysis of the reasons for adoption suggested that the temporal change in adopted flower species was related to the increasing emphasis on species with an explicit local context, especially those with instrumental value to the city. Our findings indicate the tendency for local governments to increasingly recognize their biocultural backgrounds and the ecosystem services of plants within their regions. The growing awareness of the local governments regarding their biocultural background is a positive sign for the conservation of biodiversity and ecosystem services. en-copyright= kn-copyright= en-aut-name=TsuzukiYoichi en-aut-sei=Tsuzuki en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhsakiHaruna en-aut-sei=Ohsaki en-aut-mei=Haruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaguchiYawako W. en-aut-sei=Kawaguchi en-aut-mei=Yawako W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiSayaka en-aut-sei=Suzuki en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaradaShogo en-aut-sei=Harada en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtakeYurie en-aut-sei=Otake en-aut-mei=Yurie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShinoharaNaoto en-aut-sei=Shinohara en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatsuharaKoki R. en-aut-sei=Katsuhara en-aut-mei=Koki R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Health and Environmental Risk Division, National Institute for Environmental Studies kn-affil= affil-num=2 en-affil=Department of Biological Sciences, Tokyo Metropolitan University kn-affil= affil-num=3 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=4 en-affil=Center for Ecological Research, Kyoto University kn-affil= affil-num=5 en-affil=Department of Biology, Graduate School of Science, Osaka City University kn-affil= affil-num=6 en-affil=Center for Ecological Research, Kyoto University kn-affil= affil-num=7 en-affil=Center for Ecological Research, Kyoto University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=awareness of local governments kn-keyword=awareness of local governments en-keyword=biocultural diversity kn-keyword=biocultural diversity en-keyword=ecosystem services kn-keyword=ecosystem services en-keyword=manual web scraping kn-keyword=manual web scraping en-keyword=temporal trend kn-keyword=temporal trend END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=35 article-no= start-page=28887 end-page=28895 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Thermally polymerizable phthalocyanine realizes a metal–nitrogen-doped carbon material featuring a defined single-atom catalyst motif with CO2RR activity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metal–nitrogen-doped carbon materials (MNCs) exhibit good electrocatalytic performance owing to the intrinsic advantages of carbon-based materials and the presence of isolated and stabilized metal atoms coordinated by nitrogen sites. However, conventional high-temperature pyrolysis of precursor molecules make it difficult to control the coordination structure precisely. To address this issue, here we report a new synthesis strategy for MNCs. Specifically, we design and synthesize Ni-phthalocyanine functionalized with ethynyl groups as solid-state thermal polymerization points. After depositing the Ni-phthalocyanine precursor on a carbon support and performing a thermal treatment, the resultant carbon composite material features a Ni–N4 coordination structure derived from the precursor, and enhanced porosity. This material demonstrates high catalytic activity for the CO2 reduction reaction (CO2RR). Our synthetic approach is applicable to various precursor molecules and carbon supports, paving the way for the further development of MNC-based electrode catalysts. en-copyright= kn-copyright= en-aut-name=SanoYuki en-aut-sei=Sano en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaDaichi en-aut-sei=Nakajima en-aut-mei=Daichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MannaBiplab en-aut-sei=Manna en-aut-mei=Biplab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChidaKoki en-aut-sei=Chida en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToyodaRyojun en-aut-sei=Toyoda en-aut-mei=Ryojun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakaishiShinya en-aut-sei=Takaishi en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwaseKazuyuki en-aut-sei=Iwase en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaranoKoji en-aut-sei=Harano en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshiiTakeharu en-aut-sei=Yoshii en-aut-mei=Takeharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakamotoRyota en-aut-sei=Sakamoto en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Science, Tohoku University kn-affil= affil-num=2 en-affil=Department of Chemistry, Graduate School of Science, Tohoku University kn-affil= affil-num=3 en-affil=Center for Basic Research on Materials, National Institute for Materials Science kn-affil= affil-num=4 en-affil=Institute of Multidisciplinary Research for Advanced Materials, Tohoku University kn-affil= affil-num=5 en-affil=Department of Chemistry, Graduate School of Science, Tohoku University kn-affil= affil-num=6 en-affil=Department of Chemistry, Graduate School of Science, Tohoku University kn-affil= affil-num=7 en-affil=Institute of Multidisciplinary Research for Advanced Materials, Tohoku University kn-affil= affil-num=8 en-affil=Center for Basic Research on Materials, National Institute for Materials Science kn-affil= affil-num=9 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Institute of Multidisciplinary Research for Advanced Materials, Tohoku University kn-affil= affil-num=11 en-affil=Department of Chemistry, Graduate School of Science, Tohoku University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=3 article-no= start-page=e70004 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oregon Wolfe barley genetic stocks – Research and teaching tools for next generation scientists en-subtitle= kn-subtitle= en-abstract= kn-abstract=The Oregon Wolfe Barley (OWB) mapping population (Reg. no. MP-4, NSL 554937 MAP) is a resource for genetics research and instruction. The OWBs are a set of doubled haploid barley (Hordeum vulgare L.) lines developed at Oregon State University from the F1 of a cross between Dr. Robert Wolfe's dominant and recessive marker stocks. Exhibiting a high level of genetic and phenotypic diversity, the OWBs are used throughout the world as a research tool for barley genetics. To date, these endeavors have led to 56 peer-reviewed publications, as well as three reports in the Barley Genetics Newsletter. At the same time, the OWBs are widely used as an instructor resource at the K–12, undergraduate, graduate, and professional levels. They are currently used at universities and/or institutes in German, Italy, Norway, Spain, and the United States and are currently being developed further for educational use in other countries. Genotype and phenotype data, lesson plans, and seed availability information are available herein and online. en-copyright= kn-copyright= en-aut-name=KrauseMargaret R. en-aut-sei=Krause en-aut-mei=Margaret R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ArbelaezJuan David en-aut-sei=Arbelaez en-aut-mei=Juan David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsdalÅsmund en-aut-sei=Asdal en-aut-mei=Åsmund kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BelkodjaRamzi en-aut-sei=Belkodja en-aut-mei=Ramzi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BouryNancy en-aut-sei=Boury en-aut-mei=Nancy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BlakeVictoria C. en-aut-sei=Blake en-aut-mei=Victoria C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BrownPatrick J. en-aut-sei=Brown en-aut-mei=Patrick J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CasasAna en-aut-sei=Casas en-aut-mei=Ana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=CistuéLuis en-aut-sei=Cistué en-aut-mei=Luis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Farré‐MartínezAlba en-aut-sei=Farré‐Martínez en-aut-mei=Alba kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FiskScott en-aut-sei=Fisk en-aut-mei=Scott kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FuerstGregory S. en-aut-sei=Fuerst en-aut-mei=Gregory S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=GiménezEstela en-aut-sei=Giménez en-aut-mei=Estela kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Guijarro‐RealCarla en-aut-sei=Guijarro‐Real en-aut-mei=Carla kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=GuthrieKaty en-aut-sei=Guthrie en-aut-mei=Katy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HalsteadMargaret en-aut-sei=Halstead en-aut-mei=Margaret kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HelgersonLaura en-aut-sei=Helgerson en-aut-mei=Laura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IgartuaErnesto en-aut-sei=Igartua en-aut-mei=Ernesto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=LillemoMorten en-aut-sei=Lillemo en-aut-mei=Morten kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=Martínez‐GarcíaMarina en-aut-sei=Martínez‐García en-aut-mei=Marina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=Martínez‐SubiràMariona en-aut-sei=Martínez‐Subirà en-aut-mei=Mariona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=McCouchSusan en-aut-sei=McCouch en-aut-mei=Susan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=McGheeLaurie en-aut-sei=McGhee en-aut-mei=Laurie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NickolsTravis en-aut-sei=Nickols en-aut-mei=Travis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=PetersNick en-aut-sei=Peters en-aut-mei=Nick kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=PorterRaymond en-aut-sei=Porter en-aut-mei=Raymond kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=RomagosaIgnacio en-aut-sei=Romagosa en-aut-mei=Ignacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=RuudAnja Karine en-aut-sei=Ruud en-aut-mei=Anja Karine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=SalviSilvio en-aut-sei=Salvi en-aut-mei=Silvio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=SangiorgiGiuseppe en-aut-sei=Sangiorgi en-aut-mei=Giuseppe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=SchüllerRebekka en-aut-sei=Schüller en-aut-mei=Rebekka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=SenTaner Z. en-aut-sei=Sen en-aut-mei=Taner Z. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=SorianoJosé Miguel en-aut-sei=Soriano en-aut-mei=José Miguel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=StuparRobert M. en-aut-sei=Stupar en-aut-mei=Robert M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=TingTo‐Chia en-aut-sei=Ting en-aut-mei=To‐Chia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=ViningKelly en-aut-sei=Vining en-aut-mei=Kelly kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=von KorffMaria en-aut-sei=von Korff en-aut-mei=Maria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=WallaAgatha en-aut-sei=Walla en-aut-mei=Agatha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=WangDiane R. en-aut-sei=Wang en-aut-mei=Diane R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=WaughRobbie en-aut-sei=Waugh en-aut-mei=Robbie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=WiseRoger P. en-aut-sei=Wise en-aut-mei=Roger P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=WolfeRobert en-aut-sei=Wolfe en-aut-mei=Robert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=YaoEric en-aut-sei=Yao en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=HayesPatrick M. en-aut-sei=Hayes en-aut-mei=Patrick M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= affil-num=1 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=2 en-affil=Department of Crop Sciences, University of Illinois at Urbana-Champaign kn-affil= affil-num=3 en-affil=Nordic Genetic Resource Centre kn-affil= affil-num=4 en-affil=CIHEAM-Zaragoza kn-affil= affil-num=5 en-affil=Department of Plant Pathology, Entomology, and Microbiology, Iowa State University kn-affil= affil-num=6 en-affil=Department of Plant Sciences and Plant Pathology, Montana State University kn-affil= affil-num=7 en-affil=Department of Plant Sciences, University of California-Davis kn-affil= affil-num=8 en-affil=Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC kn-affil= affil-num=9 en-affil=Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC kn-affil= affil-num=10 en-affil=AGROTECNIO-CERCA Center, Universidad de Lleida kn-affil= affil-num=11 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=12 en-affil=U.S. Department of Agriculture-Agricultural Research Service, Corn Insects and Crop Genetics Research Unit, Iowa State University kn-affil= affil-num=13 en-affil=Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid kn-affil= affil-num=14 en-affil=Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid kn-affil= affil-num=15 en-affil=Department of Agronomy and Plant Genetics, University of Minnesota kn-affil= affil-num=16 en-affil=Aardevo North America kn-affil= affil-num=17 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=18 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=19 en-affil=Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC kn-affil= affil-num=20 en-affil=Department of Plant Sciences, Norwegian University of Life Sciences kn-affil= affil-num=21 en-affil=Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid kn-affil= affil-num=22 en-affil=AGROTECNIO-CERCA Center, Universidad de Lleida kn-affil= affil-num=23 en-affil=Plant Breeding and Genetics Section, School of Integrative Plant Science, Cornell University kn-affil= affil-num=24 en-affil=Colfax-Mingo Community High School kn-affil= affil-num=25 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=26 en-affil=Department of Plant Pathology, Entomology, and Microbiology, Iowa State University kn-affil= affil-num=27 en-affil=Haupert Institute for Agricultural Studies, Huntington University kn-affil= affil-num=28 en-affil=AGROTECNIO-CERCA Center, Universidad de Lleida kn-affil= affil-num=29 en-affil=Department of Plant Sciences, Norwegian University of Life Sciences kn-affil= affil-num=30 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=31 en-affil=Department of Agricultural and Food Sciences, University of Bologna kn-affil= affil-num=32 en-affil=Department of Agricultural and Food Sciences, University of Bologna kn-affil= affil-num=33 en-affil=Department of Crop Sciences, University of Illinois at Urbana-Champaign kn-affil= affil-num=34 en-affil=Crop Improvement and Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research Service kn-affil= affil-num=35 en-affil=AGROTECNIO-CERCA Center, Universidad de Lleida kn-affil= affil-num=36 en-affil=Department of Agronomy and Plant Genetics, University of Minnesota kn-affil= affil-num=37 en-affil=Agronomy Department, Purdue University kn-affil= affil-num=38 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=39 en-affil=Institute of Plant Genetics, Heinrich-Heine-Universität Düsseldorf kn-affil= affil-num=40 en-affil=Institute of Plant Genetics, Heinrich-Heine-Universität Düsseldorf kn-affil= affil-num=41 en-affil=Agronomy Department, Purdue University kn-affil= affil-num=42 en-affil=Division of Plant Sciences, School of Life Sciences, University of Dundee kn-affil= affil-num=43 en-affil=Department of Plant Pathology, Entomology, and Microbiology, Iowa State University kn-affil= affil-num=44 en-affil=Agriculture and Agri-Food Canada kn-affil= affil-num=45 en-affil=Crop Improvement and Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research Service kn-affil= affil-num=46 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=1 article-no= start-page=189 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240827 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Post-spinel-type AB2O4 high-pressure phases in geochemistry and materials science en-subtitle= kn-subtitle= en-abstract= kn-abstract=Post-spinel-type AB2O4 compounds are stable at higher pressures than spinel phases. These compounds have garnered much interest in geo- and materials science for their geochemical importance as well as potential application as high ionic conductors and materials with strongly correlated electrons. Here, large-volume high-pressure syntheses, structural features and properties of post-spinels are reviewed. Prospects are discussed for future searches for post-spinel-type phases by applying advanced large-volume high-pressure technology. en-copyright= kn-copyright= en-aut-name=AkaogiMasaki en-aut-sei=Akaogi en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamauraKazunari en-aut-sei=Yamaura en-aut-mei=Kazunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Chemistry, Gakushuin University kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=Research Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250811 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=RNA Delivery Using a Graphene Oxide-Polyethylenimine Hybrid Inhibiting Myotube Differentiation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Graphene oxide (GO) conjugated with short polyethylenimine (PEI) chains (GO-PEI) has been designed as a candidate nanocarrier for small interfering RNA (siRNA) delivery to mammalian cells based on the efficient interaction between the positively charged GO-based platform and the negatively charged siRNA. The function and efficiency of siRNA delivery using GO-PEI were compared to those using the positive control Lipofectamine RNAiMax by analyzing the differentiation to myotubes, and myogenin gene and protein expression in C2C12 cells. RNAiMax transfection induced cellularization and reduction of both myogenin gene and protein expression, suggesting that the differentiation of C2C12 cells was triggered by gene silencing. While GO-PEI also promoted cellularization, the myogenin gene expression remained comparable to scrambled controls, whereas the protein levels were higher than those observed with RNAiMax. Mechanistically, we attributed the reduced gene silencing efficiency of GO-PEI to a poor endosomal escape, despite strong siRNA complexation. This limitation was likely due to a low buffering capacity of GO-PEI, as a significant fraction of nitrogen atoms were already protonated, reducing the availability of free amines necessary for endosomal disruption. An appropriate chemical modification to enhance siRNA release from the endosomes is therefore essential for advancing the development of GO-based platforms as versatile and efficient nanocarriers in gene therapy applications. en-copyright= kn-copyright= en-aut-name=MatsuuraKoji en-aut-sei=Matsuura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ReinaGiacomo en-aut-sei=Reina en-aut-mei=Giacomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GaoZhengfeng en-aut-sei=Gao en-aut-mei=Zhengfeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BiancoAlberto en-aut-sei=Bianco en-aut-mei=Alberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS kn-affil= affil-num=2 en-affil=CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS kn-affil= affil-num=3 en-affil=CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=5 en-affil=CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS kn-affil= en-keyword=graphene oxide kn-keyword=graphene oxide en-keyword=polyethylenimine kn-keyword=polyethylenimine en-keyword=myotubes kn-keyword=myotubes en-keyword=myogenin kn-keyword=myogenin en-keyword=small interfering RNA kn-keyword=small interfering RNA en-keyword=transfection kn-keyword=transfection END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=10 article-no= start-page=4724 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250515 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Stem Cell Factors BAM1 and WOX1 Suppressing Longitudinal Cell Division of Margin Cells Evoked by Low-Concentration Auxin in Young Cotyledon of Arabidopsis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Highly differentiated tissues and organs play essential biological functions in multicellular organisms. Coordination of organ developmental process with tissue differentiation is necessary to achieve proper development of mature organs, but mechanisms for such coordination are not well understood. We used cotyledon margin cells from Arabidopsis plant as a new model system to investigate cell elongation and cell division during organ growth and found that margin cells endured a developmental phase transition from the “elongation” phase to the “elongation and division” phase at the early stage in germinating seedlings. We also discovered that the stem cell factors BARELY ANY MERISTEM 1 (BAM1) and WUSCHEL-related homeobox1 (WOX1) are involved in the regulation of margin cell developmental phase transition. Furthermore, exogenous auxin treatment (1 nanomolar,nM) promotes cell division, especially longitudinal cell division. This promotion of cell division did not occur in bam1 and wox1 mutants. Based on these findings, we hypothesized a new “moderate auxin concentration” model which emphasizes that a moderate auxin concentration is the key to triggering the developmental transition of meristematic cells. en-copyright= kn-copyright= en-aut-name=JiangYuli en-aut-sei=Jiang en-aut-mei=Yuli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiangJian en-aut-sei=Liang en-aut-mei=Jian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangChunyan en-aut-sei=Wang en-aut-mei=Chunyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanLi en-aut-sei=Tan en-aut-mei=Li kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawanoYoji en-aut-sei=Kawano en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagawaShingo en-aut-sei=Nagawa en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Institute for Translational Brain Reaearch, Fudan University kn-affil= affil-num=2 en-affil=Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences kn-affil= affil-num=3 en-affil=Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences kn-affil= en-keyword=BAM1 kn-keyword=BAM1 en-keyword=WOX1 kn-keyword=WOX1 en-keyword=margin cells kn-keyword=margin cells en-keyword=auxin kn-keyword=auxin END start-ver=1.4 cd-journal=joma no-vol=39 cd-vols= no-issue=5 article-no= start-page=2810 end-page=2817 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Geriatric Nutritional Risk Index: A Key Indicator of Perioperative Outcome in Oldest-old Patients With Colorectal Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Colorectal cancer (CRC) presents a significant challenge in oldest-old patients (≥85 years), where surgical intervention carries substantial perioperative risks. Nutritional status is a crucial determinant of outcomes, and the Geriatric Nutritional Risk Index (GNRI) has shown promise. This prospective study aimed to validate the GNRI as a key indicator of perioperative outcomes in oldest-old patients undergoing CRC surgery, and to establish its utility in preoperative risk stratification.
Patients and Methods: This prospective study enrolled patients aged ≥85 years undergoing elective surgery for CRC. Preoperative GNRI was calculated using the formula: GNRI=14.89×serum albumin (g/dl)+41.7×[actual body weight/ideal body weight (corresponding to body mass index 22)]. Patients were stratified into two groups: GNRI >98 and GNRI ≤98. Baseline demographics, clinical characteristics, geriatric assessments (including Geriatric-8 and EuroQol 5 dimension), and postoperative complication rates were analyzed.
Results: Twenty-four patients (median age 88 years, interquartile range=86-91) were included: 11 in the GNRI >98 group and 13 in the GNRI ≤98 group. The patients with GNRI >98 demonstrated significantly better G8 scores (median 12 vs. 11, p<0.01) and EQ-5D index values (median 88 vs. 75.0, p<0.01). The postoperative complication rate was significantly higher in the GNRI ≤98 group (p=0.02).
Conclusion: Preoperative GNRI effectively identifies oldest-old patients with CRC at increased risk for postoperative complications. A GNRI ≤98 correlates with poorer nutritional status and impaired geriatric functional parameters. These findings highlight GNRI’s utility as a simple, valuable tool for preoperative risk stratification, potentially guiding interventions to optimize outcomes in this vulnerable population. en-copyright= kn-copyright= en-aut-name=TERAISHIFUMINORI en-aut-sei=TERAISHI en-aut-mei=FUMINORI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UTSUMIMASASHI en-aut-sei=UTSUMI en-aut-mei=MASASHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YOSHIDAYUSUKE en-aut-sei=YOSHIDA en-aut-mei=YUSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SHOJIRYOHEI en-aut-sei=SHOJI en-aut-mei=RYOHEI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KANAYANOBUHIKO en-aut-sei=KANAYA en-aut-mei=NOBUHIKO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MATSUMIYUKI en-aut-sei=MATSUMI en-aut-mei=YUKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SHIGEYASUKUNITOSHI en-aut-sei=SHIGEYASU en-aut-mei=KUNITOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KONDOYOSHITAKA en-aut-sei=KONDO en-aut-mei=YOSHITAKA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ITAGAKISHIORI en-aut-sei=ITAGAKI en-aut-mei=SHIORI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TAMURARIE en-aut-sei=TAMURA en-aut-mei=RIE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MATSUOKAYOSHIKAZU en-aut-sei=MATSUOKA en-aut-mei=YOSHIKAZU kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FUJIWARATOSHIYOSHI en-aut-sei=FUJIWARA en-aut-mei=TOSHIYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=INAGAKIMASARU en-aut-sei=INAGAKI en-aut-mei=MASARU kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Perioperative Management Center, Okayama University Hospital kn-affil= affil-num=10 en-affil=Perioperative Management Center, Okayama University Hospital kn-affil= affil-num=11 en-affil=Perioperative Management Center, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Surgery, National Hospital Organization Fukuyama Medical Center kn-affil= en-keyword=Geriatric nutritional risk index kn-keyword=Geriatric nutritional risk index en-keyword=oldest‑old kn-keyword=oldest‑old en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=short‑term outcome kn-keyword=short‑term outcome END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=9 article-no= start-page=396 end-page=406 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250915 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-world Experience of Embolization for Intracranial Tumors in Japan: Analysis of 2,756 Cases from Japanese Registry of NeuroEndovascular Therapy 4 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Embolization of intracranial tumors is predominantly performed in Japan, primarily before neurosurgical resection. The Japanese Registry of NeuroEndovascular Therapy (JR-NET) Study Group, established in 2005, aims to clarify the factors influencing the outcomes of neuroendovascular treatment. Japanese Registry of NeuroEndovascular Therapy 4 is a nationwide, multicenter retrospective observational study that evaluates real-world data on intracranial tumor embolization in Japan. Japanese Registry of NeuroEndovascular Therapy 4 is based on data collected from 166 neurosurgical centers in Japan between January 2015 and December 2019. Of 63,230 patients, 2,664 (4.2%) with intracranial tumors underwent embolization. The primary endpoint was the proportion of patients with a modified Rankin scale (mRS) score of 0-2 at 30 days post-procedure. Secondary endpoints included procedure-related complications. Among the 2,664 patients, 61 records lacked sufficient data, leaving 2,603 patients (1,612 females, median age: 61 years [interquartile range 51-71]). The proportion of patients with mRS scores ≤2 at 30 days after the procedure was 86.9%. The overall incidence of procedure-related complications was 4.8%, with 1.8% hemorrhagic, 2.0% ischemic, and 1.0% classified as other complications. In the multivariate analysis, general anesthesia and embolization of vessels other than the external carotid artery were identified as risk factors for the development of complications. Meningioma cases had a complication rate of 4.3%, with major complications occurring in 3.5%. Hemangioblastoma cases had a 14.9% complication rate, with major complications at 9.9%. Japanese Registry of NeuroEndovascular Therapy 4 provides comprehensive real-world data on intracranial tumor embolization in Japan, identifying risk factors to inform and improve the safe practice of intracranial tumor embolization in neuroendovascular therapy. en-copyright= kn-copyright= en-aut-name=HARUMAJun en-aut-sei=HARUMA en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SUGIUKenji en-aut-sei=SUGIU en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HISHIKAWATomohito en-aut-sei=HISHIKAWA en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SOUTOMEYuta en-aut-sei=SOUTOME en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EBISUDANIYuki en-aut-sei=EBISUDANI en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KIMURARyu en-aut-sei=KIMURA en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EDAKIHisanori en-aut-sei=EDAKI en-aut-mei=Hisanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KAWAKAMIMasato en-aut-sei=KAWAKAMI en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MURAISatoshi en-aut-sei=MURAI en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HIRAMATSUMasafumi en-aut-sei=HIRAMATSU en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TANAKAShota en-aut-sei=TANAKA en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SATOWTetsu en-aut-sei=SATOW en-aut-mei=Tetsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IIHARAKoji en-aut-sei=IIHARA en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IMAMURAHirotoshi en-aut-sei=IMAMURA en-aut-mei=Hirotoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ISHIIAkira en-aut-sei=ISHII en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MATSUMARUYuji en-aut-sei=MATSUMARU en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SAKAIChiaki en-aut-sei=SAKAI en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YOSHIMURAShinichi en-aut-sei=YOSHIMURA en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SAKAINobuyuki en-aut-sei=SAKAI en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=Japanese Registry of Neuroendovascular Therapy (JR-NET) Investigators en-aut-sei=Japanese Registry of Neuroendovascular Therapy (JR-NET) Investigators en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurosurgery, Kawasaki Medical School kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurosurgery, Kawasaki Medical School kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurosurgery, Kindai University kn-affil= affil-num=13 en-affil=Department of Neurosurgery, National Cerebral and Cardiovascular Center kn-affil= affil-num=14 en-affil=Department of Neurosurgery, National Cerebral and Cardiovascular Center kn-affil= affil-num=15 en-affil=Department of Neurosurgery, Juntendo University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Neurosurgery, Institute of Medicine, University of Tsukuba kn-affil= affil-num=17 en-affil=Department of Neurosurgery, Kyoto University kn-affil= affil-num=18 en-affil=Department of Neurosurgery, Hyogo Medical University kn-affil= affil-num=19 en-affil=Department of Neurological Surgery, Shimizu Hospital kn-affil= affil-num=20 en-affil= kn-affil= en-keyword=complication kn-keyword=complication en-keyword=intracranial tumor kn-keyword=intracranial tumor en-keyword=embolization kn-keyword=embolization en-keyword=Japanese registry kn-keyword=Japanese registry END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=9 article-no= start-page=090101 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250901 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fundamentals and advances in transverse thermoelectrics en-subtitle= kn-subtitle= en-abstract= kn-abstract=Transverse thermoelectric effects interconvert charge and heat currents in orthogonal directions due to the breaking of either time-reversal symmetry or structural symmetry, enabling simple and versatile thermal energy harvesting and solid-state cooling/heating within single materials. In comparison to the complex module structures required for the conventional Seebeck and Peltier effects, the transverse thermoelectric effects provide the complete device structures, potentially resolving the fundamental issue of multi-module degradation of thermoelectric conversion performance. This review article provides an overview of all currently known transverse thermoelectric conversion phenomena and principles, as well as their characteristics, and reclassifies them in a unified manner. The performance of the transverse thermoelectric generator, refrigerator, and active cooler is formulated, showing that thermal boundary conditions play an essential role in discussion on their behaviors. Examples of recent application research and material development in transverse thermoelectrics are also introduced, followed by a discussion of future prospects. en-copyright= kn-copyright= en-aut-name=AdachiHiroto en-aut-sei=Adachi en-aut-mei=Hiroto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AndoFuyuki en-aut-sei=Ando en-aut-mei=Fuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiraiTakamasa en-aut-sei=Hirai en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ModakRajkumar en-aut-sei=Modak en-aut-mei=Rajkumar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GraysonMatthew A. en-aut-sei=Grayson en-aut-mei=Matthew A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchidaKen-ichi en-aut-sei=Uchida en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Research Center for Magnetic and Spintronic Materials, National Institute for Materials Science kn-affil= affil-num=3 en-affil=Research Center for Magnetic and Spintronic Materials, National Institute for Materials Science kn-affil= affil-num=4 en-affil=Research Center for Magnetic and Spintronic Materials, National Institute for Materials Science kn-affil= affil-num=5 en-affil=Department of Electrical and Computer Engineering, Northwestern University kn-affil= affil-num=6 en-affil=Research Center for Magnetic and Spintronic Materials, National Institute for Materials Science kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=8 article-no= start-page=e70325 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cardiotoxicity Assessment of EGFR Tyrosine Kinase Inhibitors Using Human iPS Cell‐Derived Cardiomyocytes and FDA Adverse Events Reporting System en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent advances in the development of anti-cancer drugs have contributed to prolonged survival of cancer patients. In contrast, drug-induced cardiotoxicity, particularly cardiac contractile dysfunction, is of growing concern in cancer treatment. Therefore, it is important to understand the risks of anti-cancer drug-induced cardiac contractile dysfunction in drug development. We have previously developed image-based motion analysis using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to assess the effect of drugs on contractility. However, the utility and predictive potential of image-based motion analysis using hiPSC-CMs for anti-cancer drug-induced cardiac contractile dysfunction have not been well understood. Here we focused on epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and investigated the correlation between the hiPSC-CMs data and clinical signals of adverse events related to cardiac contractile dysfunction. We examined the effects of the four EGFR-TKIs, osimertinib, gefitinib, afatinib, and erlotinib, on the contractility of hiPSC-CMs using image-based motion analysis. We found that osimertinib decreased contraction velocity and deformation distance in a dose- and time-dependent manner, whereas gefitinib, afatinib, and erlotinib had little effect on these parameters. Next, we examined the real-world data of the EGFR-TKIs using FDA Adverse Event Reporting System (FAERS; JAPIC AERS). Only osimertinib showed significant clinical signals of adverse events related to cardiac contractile dysfunction. These data suggest that hiPSC-CM data correlate with clinical signals in FAERS analysis for four EGFR-TKIs. Thus, image-based motion analysis using hiPSC-CMs can be a useful platform for predicting the risk of anti-cancer drug-induced cardiac contractile dysfunction in patients. en-copyright= kn-copyright= en-aut-name=YanagidaShota en-aut-sei=Yanagida en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawagishiHiroyuki en-aut-sei=Kawagishi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SaitoMitsuo en-aut-sei=Saito en-aut-mei=Mitsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KandaYasunari en-aut-sei=Kanda en-aut-mei=Yasunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Division of Pharmacology, National Institute of Health Sciences (NIHS) kn-affil= affil-num=2 en-affil=Division of Pharmacology, National Institute of Health Sciences (NIHS) kn-affil= affil-num=3 en-affil=Japan Pharmaceutical Information Center (JAPIC) kn-affil= affil-num=4 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Pharmacology, National Institute of Health Sciences (NIHS) kn-affil= en-keyword=cardiomyocytes kn-keyword=cardiomyocytes en-keyword=cardiotoxicity kn-keyword=cardiotoxicity en-keyword=contractility kn-keyword=contractility en-keyword=EGFR-tyrosine kinase inhibitor kn-keyword=EGFR-tyrosine kinase inhibitor en-keyword=FAERS kn-keyword=FAERS en-keyword=human iPS cell kn-keyword=human iPS cell END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=2535955 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250807 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Quantitative measurements of transverse thermoelectric generation and cooling performances in SmCo5/Bi0.2Sb1.8Te3-based artificially tilted multilayer module en-subtitle= kn-subtitle= en-abstract= kn-abstract=The transverse thermoelectric generation and cooling performances in a thermopile module composed of recently developed SmCo5/Bi0.2Sb1.8Te3 artificially tilted multilayers are evaluated quantitatively. When a large temperature difference of 405°C is applied to the SmCo5/Bi0.2Sb1.8Te3-based module, the open-circuit voltage and output power reach 0.51 V and 0.80 W, respectively. The corresponding maximum power density is 0.16 W/cm2, even if the power is normalized by the device area including areas that do not contribute to the power generation, such as epoxy resin, electrodes, and insulating layers. The maximum energy conversion efficiency for our module in this condition is experimentally determined to be 0.92%. Under the cooling operation, the same module exhibits the maximum temperature difference of 9.0°C and heat flow at the cold side of 1.6 W. Although these values are lower than the ideal thermoelectric performance expected from the material parameters due to the imperfections associated with modularization, the systematic investigations reported here clarify a potential of the SmCo5/Bi0.2Sb1.8Te3 artificially tilted multilayers as thermoelectric generators and cooling devices. en-copyright= kn-copyright= en-aut-name=MurataMasayuki en-aut-sei=Murata en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AndoFuyuki en-aut-sei=Ando en-aut-mei=Fuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiraiTakamasa en-aut-sei=Hirai en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AdachiHiroto en-aut-sei=Adachi en-aut-mei=Hiroto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UchidaKen-ichi en-aut-sei=Uchida en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Research Institute for Energy Conservation, National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=2 en-affil=Research Center for Magnetic and Spintronic Materials, National Institute for Materials Science kn-affil= affil-num=3 en-affil=Research Center for Magnetic and Spintronic Materials, National Institute for Materials Science kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=5 en-affil=Research Center for Magnetic and Spintronic Materials, National Institute for Materials Science kn-affil= en-keyword=Transverse thermoelectric generation kn-keyword=Transverse thermoelectric generation en-keyword=electronic cooling kn-keyword=electronic cooling en-keyword=thermoelectric module kn-keyword=thermoelectric module en-keyword=permanent magnet kn-keyword=permanent magnet END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=24040 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250705 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lactose fermenting enteroinvasive Escherichia coli from diarrhoeal cases confers enhanced virulence en-subtitle= kn-subtitle= en-abstract= kn-abstract=Enteroinvasive Escherichia coli (EIEC), known for causing bacillary dysentery akin to Shigella species, comprises both lactose-fermenting (LF) and non-lactose-fermenting (NLF) isolates. While NLF-EIEC is a well-established pathogen associated with acute dysentery and harbours classical Shigella-like virulence factors, the role of LF-EIEC in human disease remains underexplored. In this study, we sought to characterize LF-EIEC clinical isolates and assessed their pathogenic potential in comparison to NLF-EIEC. Among 13,682 diarrhoeal stool specimens, six LF and nine NLF-EIEC were isolated, predominantly belonging to serogroups O28ac, O125, O136, and O152. Unlike other E. coli, all the EIEC isolates were non-motile. Both the types of EIEC had multiple plasmids harbouring several virulence encoding genes (ipaBCD, ial, virF, sig, sepA and ipaH). Resistance to recent generation antibiotics were mostly confined to NLF-EIEC but some of the LF-EIEC were resistant only to ceftriaxone. Higher invasion ability and significant increase in the expression of virulence encoding genes by the LF-EIEC (p < 0.05) were noted during infection to Int407 cell-line. Additionally, LF-EIEC exhibited extensive colonization of the mouse intestine and expressed severe keratoconjunctivitis in guinea pigs. Together, our findings highlight LF-EIEC as an emerging pathogenic variant warranting heightened surveillance and comprehensive investigation to better understand its epidemiological and clinical significance. en-copyright= kn-copyright= en-aut-name=GhoshDebjani en-aut-sei=Ghosh en-aut-mei=Debjani kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HalderProlay en-aut-sei=Halder en-aut-mei=Prolay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SamantaProsenjit en-aut-sei=Samanta en-aut-mei=Prosenjit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChowdhuryGoutam en-aut-sei=Chowdhury en-aut-mei=Goutam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShawSreeja en-aut-sei=Shaw en-aut-mei=Sreeja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BosePuja en-aut-sei=Bose en-aut-mei=Puja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=RoyDeboleena en-aut-sei=Roy en-aut-mei=Deboleena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=RoyNivedita en-aut-sei=Roy en-aut-mei=Nivedita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KitaharaKei en-aut-sei=Kitahara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=RamamurthyThandavarayan en-aut-sei=Ramamurthy en-aut-mei=Thandavarayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KoleyHemanta en-aut-sei=Koley en-aut-mei=Hemanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=DuttaShanta en-aut-sei=Dutta en-aut-mei=Shanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MukhopadhyayAsish Kumar en-aut-sei=Mukhopadhyay en-aut-mei=Asish Kumar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=2 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=3 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=4 en-affil=Collaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=5 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=6 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=7 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=8 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=9 en-affil=Collaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=10 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=11 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=12 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=14 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= en-keyword=Antibiotic resistance kn-keyword=Antibiotic resistance en-keyword=Bacterial infections kn-keyword=Bacterial infections en-keyword=Diarrhoea kn-keyword=Diarrhoea en-keyword=Enteroinvasive Escherichia coli kn-keyword=Enteroinvasive Escherichia coli en-keyword=Keratoconjunctivitis kn-keyword=Keratoconjunctivitis en-keyword=Pathogenesis kn-keyword=Pathogenesis END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=7 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Animal–chlorophyte photosymbioses: evolutionary origins and ecological diversity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosynthetic symbiosis occurs across diverse animal lineages, including Porifera, Cnidaria, Xenacoelomorpha and Mollusca. These associations between animal hosts and photosynthetic algae often involve the exchange of essential macronutrients, supporting adaptation to a wide range of aquatic environments. A small yet taxonomically widespread subset of animals host photosymbionts from the core chlorophytes, a phylogenetically expansive clade of green algae. These rare instances of ‘plant-like’ animals have arisen independently across distantly related lineages, resulting in striking ecological and physiological diversity. Although such associations provide valuable insights into the evolution of symbiosis and adaptation to novel ecological niches, animal–chlorophyte photosymbioses remain relatively understudied. Here, we present an overview of photosymbioses between animals and chlorophytes, highlighting their independent evolutionary origins, ecological diversity and emerging genomic resources. Focusing on Porifera, Cnidaria and Xenacoelomorpha, we review shared and lineage-specific adaptations underlying these associations. We also contrast them with dinoflagellate-based systems to demonstrate their distinct ecological and cellular features. Our work sets the stage for elucidating the molecular mechanisms underlying these associations, enhancing our understanding of how interspecies interactions drive adaptation to unique ecological niches through animal–chlorophyte symbiosis. en-copyright= kn-copyright= en-aut-name=LiaoIsabel Jiah-Yih en-aut-sei=Liao en-aut-mei=Isabel Jiah-Yih kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakagamiTosuke en-aut-sei=Sakagami en-aut-mei=Tosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LewinThomas D. en-aut-sei=Lewin en-aut-mei=Thomas D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BaillyXavier en-aut-sei=Bailly en-aut-mei=Xavier kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamadaMayuko en-aut-sei=Hamada en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LuoYi-Jyun en-aut-sei=Luo en-aut-mei=Yi-Jyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Biodiversity Research Center, Academia Sinica kn-affil= affil-num=2 en-affil=Biodiversity Research Center, Academia Sinica kn-affil= affil-num=3 en-affil=Biodiversity Research Center, Academia Sinica kn-affil= affil-num=4 en-affil=Laboratoire des Modèles Marins Multicellulaires, Station Biologique de Roscoff kn-affil= affil-num=5 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=6 en-affil=Biodiversity Research Center, Academia Sinica kn-affil= en-keyword=hydra kn-keyword=hydra en-keyword=photosymbiosis kn-keyword=photosymbiosis en-keyword=green algae kn-keyword=green algae en-keyword=acoels kn-keyword=acoels en-keyword=sponges kn-keyword=sponges END start-ver=1.4 cd-journal=joma no-vol=149 cd-vols= no-issue=1 article-no= start-page=36 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250426 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cerebral Braak stage and amygdala granular fuzzy astrocyte status have independent effects on neuronal 3R-tau and 4R-tau accumulations in the olfactory bulb, respectively, in cases with low to intermediate AD neuropathologic change en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YokotaOsamu en-aut-sei=Yokota en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MikiTomoko en-aut-sei=Miki en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Nakashima-YasudaHanae en-aut-sei=Nakashima-Yasuda en-aut-mei=Hanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshizuHideki en-aut-sei=Ishizu en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiTakashi en-aut-sei=Haraguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyashitaAkinori en-aut-sei=Miyashita en-aut-mei=Akinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkeuchiTakeshi en-aut-sei=Ikeuchi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HasegawaMasato en-aut-sei=Hasegawa en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishikawaNaoto en-aut-sei=Nishikawa en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakenoshitaShintaro en-aut-sei=Takenoshita en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TeradaSeishi en-aut-sei=Terada en-aut-mei=Seishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Okayama University Medical School kn-affil= affil-num=4 en-affil=Okayama University Medical School kn-affil= affil-num=5 en-affil=Department of Neurology, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Molecular Genetics, Brain Research Institute, Niigata University kn-affil= affil-num=7 en-affil=Department of Molecular Genetics, Brain Research Institute, Niigata University kn-affil= affil-num=8 en-affil=Dementia Research Project, Tokyo Metropolitan Institute of Medical Science kn-affil= affil-num=9 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=156 cd-vols= no-issue=2 article-no= start-page=473 end-page=479.e1 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dried blood spot proteome identifies subclinical interferon signature in neonates with type I interferonopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Type I interferonopathy is characterized by aberrant upregulation of type I interferon signaling. The mRNA interferon signature is a useful marker for activation of the interferon pathway and for diagnosis of type I interferonopathy; however, early diagnosis is challenging.
Objective: This study sought to identify the proteomic interferon signature in dried blood spot (DBS) samples. The aim was to evaluate the usefulness of the interferon signature for neonatal screening and to gain insight into presymptomatic state of neonates with inborn errors of immunity (IEIs).
Methods: DBS samples from healthy newborns/adults, patients with type I interferonopathy or other IEIs as well as from neonates with viral infections, including some samples obtained during the presymptomatic neonatal period, were examined by nontargeted proteome analyses. Expression of interferon-stimulated genes (ISGs) was evaluated and a DBS-interferon signature was defined. Differential expression/pathway analysis was also performed.
Results: The ISG products IFIT5, ISG15, and OAS2 were detected. Expression of IFIT5 and ISG15 was upregulated significantly in individuals with type I interferonopathy. We defined the sum of the z scores for these as the DBS-interferon signature, and found that patients with IEIs other than type I interferonopathy, such as chronic granulomatous disease (CGD), also showed significant elevation. Additionally, neonatal samples of type I interferonopathy and CGD patients showed high interferon signatures. Pathway analysis of neonatal CGD samples revealed upregulation of systemic lupus erythematosus–like pathways.
Conclusion: Upregulation of the interferon pathway exists already at birth—not only in neonates with type I interferonopathy but also in other IEIs, including CGD. en-copyright= kn-copyright= en-aut-name=NihiraHiroshi en-aut-sei=Nihira en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaDaisuke en-aut-sei=Nakajima en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IzawaKazushi en-aut-sei=Izawa en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawashimaYusuke en-aut-sei=Kawashima en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShibataHirofumi en-aut-sei=Shibata en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KonnoRyo en-aut-sei=Konno en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigashiguchiMotoko en-aut-sei=Higashiguchi en-aut-mei=Motoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyamotoTakayuki en-aut-sei=Miyamoto en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Nishitani-IsaMasahiko en-aut-sei=Nishitani-Isa en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HiejimaEitaro en-aut-sei=Hiejima en-aut-mei=Eitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HondaYoshitaka en-aut-sei=Honda en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsubayashiTadashi en-aut-sei=Matsubayashi en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshiharaTakashi en-aut-sei=Ishihara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IwataNaomi en-aut-sei=Iwata en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OhwadaYoko en-aut-sei=Ohwada en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TomotakiSeiichi en-aut-sei=Tomotaki en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawaiMasahiko en-aut-sei=Kawai en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MurakamiKosaku en-aut-sei=Murakami en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhnishiHidenori en-aut-sei=Ohnishi en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=IshimuraMasataka en-aut-sei=Ishimura en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=OkadaSatoshi en-aut-sei=Okada en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YamashitaMotoi en-aut-sei=Yamashita en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MorioTomohiro en-aut-sei=Morio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=HoshinoAkihiro en-aut-sei=Hoshino en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KaneganeHirokazu en-aut-sei=Kanegane en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ImaiKohsuke en-aut-sei=Imai en-aut-mei=Kohsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NakamuraYasuko en-aut-sei=Nakamura en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=NonoyamaShigeaki en-aut-sei=Nonoyama en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=UchiyamaToru en-aut-sei=Uchiyama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=OnoderaMasafumi en-aut-sei=Onodera en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=IshikawaTakashi en-aut-sei=Ishikawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawaiToshinao en-aut-sei=Kawai en-aut-mei=Toshinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=TakitaJunko en-aut-sei=Takita en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=NishikomoriRyuta en-aut-sei=Nishikomori en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=OharaOsamu en-aut-sei=Ohara en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=YasumiTakahiro en-aut-sei=Yasumi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= affil-num=1 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=3 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=7 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Pediatrics, Seirei Hamamatsu General Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Nara Medical University kn-affil= affil-num=14 en-affil=Department of Pediatrics, Okayama University kn-affil= affil-num=15 en-affil=Department of Infection and Immunology, Aichi Children’s Health and Medical Center kn-affil= affil-num=16 en-affil=Department of Pediatrics, Dokkyo Medical University School of Medicine kn-affil= affil-num=17 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Neonatology, Kyoto University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Pediatrics, Gifu University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=22 en-affil=Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences kn-affil= affil-num=23 en-affil=Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=24 en-affil=Laboratory of Immunology and Molecular Medicine, Advanced Research Initiative, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=25 en-affil=Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=26 en-affil=Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=27 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=28 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=29 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=30 en-affil=Department of Human Genetics, National Center for Child Health and Development kn-affil= affil-num=31 en-affil=Department of Human Genetics, National Center for Child Health and Development kn-affil= affil-num=32 en-affil=Division of Immunology, National Center for Child Health and Development kn-affil= affil-num=33 en-affil=Division of Immunology, National Center for Child Health and Development kn-affil= affil-num=34 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=35 en-affil=Department of Pediatrics and Child Health, Kurume University School of Medicine kn-affil= affil-num=36 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=37 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= en-keyword=Inborn errors of immunity kn-keyword=Inborn errors of immunity en-keyword=interferonopathy kn-keyword=interferonopathy en-keyword=signature kn-keyword=signature en-keyword=proteome kn-keyword=proteome en-keyword=dried blood spot kn-keyword=dried blood spot en-keyword=CGD kn-keyword=CGD en-keyword=WAS kn-keyword=WAS en-keyword=newborn kn-keyword=newborn en-keyword=neonate kn-keyword=neonate END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=roaf042 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recommendations for the treatment of juvenile idiopathic arthritis with oligoarthritis or polyarthritis from the 2024 update of the Japan College of Rheumatology Clinical Practice Guidelines for the management of rheumatoid arthritis including juvenile idiopathic arthritis with oligoarthritis or polyarthritis – secondary publication en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To conduct systematic reviews (SRs) and develop clinical practice guidelines (CPGs) for managing juvenile idiopathic arthritis (JIA) with oligoarthritis or polyarthritis.
Methods: The Grading of Recommendations, Assessment, Development, and Evaluation methodology was employed to carry out SRs and formulate the CPGs. An expert panel, including patients, paediatric and nonpaediatric rheumatologists, guideline specialists, and patient representatives, used the Delphi method to discuss and agree on the recommendations.
Results: Six clinical questions (CQs) on the efficacy and safety of medical treatments were evaluated. These included CQ1 on methotrexate (MTX), CQ2 on non-MTX conventional synthetic disease-modifying antirheumatic drugs, CQ3 on glucocorticoids, CQ4 on tumour necrosis factor inhibitors, CQ5 on interleukin-6 inhibitors, and CQ6 on Janus kinase inhibitors. Two randomized controlled trials were identified for CQ1, three for CQ2, two for CQ3, eight for CQ4, two for CQ5, and two for CQ6. Based on these evaluations, three strong and three conditional recommendations were established. The CPGs have been endorsed by the Japan College of Rheumatology and the Pediatric Rheumatology Association of Japan.
Conclusions: The SRs provided the necessary evidence to develop the CPGs, which are intended to guide not only paediatric but also nonpaediatric rheumatologists, caregivers, patients, and their families in treatment decision-making. en-copyright= kn-copyright= en-aut-name=MiyamaeTakako en-aut-sei=Miyamae en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkamotoNami en-aut-sei=Okamoto en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoueYuzaburo en-aut-sei=Inoue en-aut-mei=Yuzaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KubotaTomohiro en-aut-sei=Kubota en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EbatoTakasuke en-aut-sei=Ebato en-aut-mei=Takasuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IrabuHitoshi en-aut-sei=Irabu en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamedaHideto en-aut-sei=Kameda en-aut-mei=Hideto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanekoYuko en-aut-sei=Kaneko en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuboHiroshi en-aut-sei=Kubo en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MitsunagaKanako en-aut-sei=Mitsunaga en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MoriMasaaki en-aut-sei=Mori en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakajimaAyako en-aut-sei=Nakajima en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NishimuraKenichi en-aut-sei=Nishimura en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OhkuboNaoaki en-aut-sei=Ohkubo en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SatoTomomi en-aut-sei=Sato en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SugitaYuko en-aut-sei=Sugita en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakanashiSatoshi en-aut-sei=Takanashi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TanakaTakayuki en-aut-sei=Tanaka en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=UmebayashiHiroaki en-aut-sei=Umebayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YamanishiShingo en-aut-sei=Yamanishi en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=FusamaMie en-aut-sei=Fusama en-aut-mei=Mie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HirataShintaro en-aut-sei=Hirata en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KishimotoMitsumasa en-aut-sei=Kishimoto en-aut-mei=Mitsumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KohnoMasataka en-aut-sei=Kohno en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KojimaMasayo en-aut-sei=Kojima en-aut-mei=Masayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KojimaToshihisa en-aut-sei=Kojima en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MorinobuAkio en-aut-sei=Morinobu en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=SugiharaTakahiko en-aut-sei=Sugihara en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=TanakaEiichi en-aut-sei=Tanaka en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=YajimaNobuyuki en-aut-sei=Yajima en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=YanaiRyo en-aut-sei=Yanai en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawahitoYutaka en-aut-sei=Kawahito en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=HarigaiMasayoshi en-aut-sei=Harigai en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= affil-num=1 en-affil=Department of Pediatric Rheumatology, Institute of Rheumatology, Tokyo Women’s Medical University Hospital kn-affil= affil-num=2 en-affil=Department of Pediatrics, Osaka Rosai Hospital, Japan Organization of Occupational Health and Safety kn-affil= affil-num=3 en-affil=Department of General Medical Science, Graduate School of Medicine, Chiba University kn-affil= affil-num=4 en-affil=Department of Pediatrics, Kagoshima Prefectural Satsunan Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kitasato University kn-affil= affil-num=6 en-affil=Department of Pediatrics and Development Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University kn-affil= affil-num=7 en-affil=Division of Rheumatology, Department of Internal Medicine, Toho University kn-affil= affil-num=8 en-affil=Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=10 en-affil=Department of Allergy and Rheumatology, Chiba Children's Hospital kn-affil= affil-num=11 en-affil=Department of Lifetime Clinical Immunology, Tokyo Medical and Dental University kn-affil= affil-num=12 en-affil=Center for Rheumatic Diseases, Mie University Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Yokohama City University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Iizuka Hospital kn-affil= affil-num=15 en-affil=Clinical Education Center For Physicians, Shiga University of Medical Science kn-affil= affil-num=16 en-affil=Department of Pediatrics, School of Medicine, Osaka Medical and Pharmaceutical University kn-affil= affil-num=17 en-affil=Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=18 en-affil=Department of Pediatrics, Japanese Red Cross Otsu Hospital kn-affil= affil-num=19 en-affil=Department of Rheumatology and Infectious Diseases, Miyagi Children’s Hospital kn-affil= affil-num=20 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Pediatrics, Nippon Medical School kn-affil= affil-num=22 en-affil=Health Sciences Department of Nursing, Kansai University of International Studies kn-affil= affil-num=23 en-affil=Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital kn-affil= affil-num=24 en-affil=Department of Nephrology and Rheumatology, Kyorin University School of Medicine kn-affil= affil-num=25 en-affil=Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=26 en-affil=Graduate School of Medical Sciences, Nagoya City University kn-affil= affil-num=27 en-affil=Department of Orthopedic Surgery, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=28 en-affil=Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=29 en-affil=Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine kn-affil= affil-num=30 en-affil=Division of Rheumatology, Department of Internal Medicine, School of Medicine, Tokyo Women's Medical University kn-affil= affil-num=31 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= affil-num=32 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= affil-num=33 en-affil=Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=34 en-affil=Division of Rheumatology, Department of Internal Medicine, School of Medicine, Tokyo Women's Medical University kn-affil= en-keyword=Clinical practice guidelines kn-keyword=Clinical practice guidelines en-keyword=baricitinib kn-keyword=baricitinib en-keyword=GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) kn-keyword=GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) en-keyword=juvenile idiopathic arthritis kn-keyword=juvenile idiopathic arthritis en-keyword=systematic review kn-keyword=systematic review END start-ver=1.4 cd-journal=joma no-vol=98 cd-vols= no-issue=6 article-no= start-page=uoaf044 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250516 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Redox-potential-controlled intermolecular [2 + 2] cycloaddition of styrenes for the regio- and diastereoselective synthesis of multisubstituted halogenocyclobutanes en-subtitle= kn-subtitle= en-abstract= kn-abstract=The redox potential is an important factor for controlling the outcome of photoredox catalysis. Particularly, the selective oxidation of substrates and the control over the reactions are challenging when using photoredox catalysts that have high excited-state reduction potentials. In this study, a redox-potential-controlled intermolecular [2 + 2] cycloaddition of styrenes using a thioxanthylium organophotoredox (TXT) catalyst has been developed. This TXT catalyst selectively oxidizes β-halogenostyrenes and smoothly promotes the subsequent intermolecular [2 + 2] cycloadditions to give multisubstituted halogenocyclobutanes with excellent regio- and diastereoselectivity, which has not been effectively achieved by the hitherto reported representative photoredox catalysts. The synthesized halogenocyclobutanes exhibit interesting free radical scavenging activity. The present reaction contributes to the field of redox-potential-controlled electron transfer chemistry. en-copyright= kn-copyright= en-aut-name=MizutaniAsuka en-aut-sei=Mizutani en-aut-mei=Asuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KondoMomo en-aut-sei=Kondo en-aut-mei=Momo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItakuraShoko en-aut-sei=Itakura en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakamuraHiroyoshi en-aut-sei=Takamura en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HoshinoYujiro en-aut-sei=Hoshino en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishikawaMakiya en-aut-sei=Nishikawa en-aut-mei=Makiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KadotaIsao en-aut-sei=Kadota en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KusamoriKosuke en-aut-sei=Kusamori en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaKenta en-aut-sei=Tanaka en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science kn-affil= affil-num=3 en-affil=Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environment and Information Sciences, Yokohama National University kn-affil= affil-num=6 en-affil=Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Laboratory of Cellular Drug Discovery and Development, Faculty of Pharmaceutical Sciences, Tokyo University of Science kn-affil= affil-num=9 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=redox potential kn-keyword=redox potential en-keyword=photoredox catalysis kn-keyword=photoredox catalysis en-keyword=[2 + 2] cycloaddition kn-keyword=[2 + 2] cycloaddition END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=1 article-no= start-page=144 end-page=156 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241109 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lymphadenectomy and chemotherapy are effective treatments for patients with 2023 international federation of gynecology and obstetrics stage IIC-high risk endometrial cancer in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background In early-stage endometrial cancer (EC), the treatment of aggressive histological subtypes (endometrioid carcinoma grade 3, serous carcinoma, clear-cell carcinoma, undifferentiated carcinoma, mixed carcinoma, and carcinosarcoma) is controversial. We aimed to investigate the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IC and stage IIC EC according to the 2023 classification.
Methods We retrospectively identified patients with FIGO 2023 stage IC, IIC-intermediate risk (IIC-I), and IIC-high risk (IIC-H) EC who underwent adjuvant therapy or observation after surgery at eight medical institutions from 2004 to 2023. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan–Meier estimates and univariate and multivariate analyses.
Results The PFS and OS were significantly worse in patients with FIGO 2023 stage IIC-H EC than in those with FIGO 2023 stage IIC-I EC (PFS: p = 0.008 and OS: p = 0.006). According to the FIGO 2023 stage IIC-H classification, lymphadenectomy and chemotherapy resulted in better prognoses regarding both PFS and OS (p < 0.001 for both) than other treatments. Our findings suggest that lymphadenectomy and chemotherapy effectively reduced vaginal stump and lymph node metastases in FIGO 2023 stage IIC-H EC (p < 0.001 and p = 0.008, respectively). Furthermore, in the multivariate analysis, not undergoing lymphadenectomy or chemotherapy were independent predictors of recurrence and poor prognoses in patients with FIGO 2023 stage IIC-H EC (p < 0.001 and p = 0.031, respectively).
Conclusion Lymphadenectomy and chemotherapy resulted in better prognoses regarding both recurrence and survival in patients with FIGO 2023 stage IIC high-risk EC. en-copyright= kn-copyright= en-aut-name=TaniYoshinori en-aut-sei=Tani en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YorimitsuMasae en-aut-sei=Yorimitsu en-aut-mei=Masae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekiNoriko en-aut-sei=Seki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanishiMie en-aut-sei=Nakanishi en-aut-mei=Mie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItouHironori en-aut-sei=Itou en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimizuMiyuki en-aut-sei=Shimizu en-aut-mei=Miyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoDan en-aut-sei=Yamamoto en-aut-mei=Dan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakaharaEtsuko en-aut-sei=Takahara en-aut-mei=Etsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Kagawa Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, National Organization Fukuyama Medical Center kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Fukuyama City Hospital kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Endometrial cancer kn-keyword=Endometrial cancer en-keyword=FIGO 2023 kn-keyword=FIGO 2023 en-keyword=Stage IIC high risk kn-keyword=Stage IIC high risk en-keyword=Lymphadenectomy kn-keyword=Lymphadenectomy en-keyword=Chemotherapy kn-keyword=Chemotherapy END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=From sewage sludge to agriculture: governmental initiatives, technologies, and sustainable practices in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sewage sludge (SS), an underutilized but valuable resource for agriculture, contains essential nutrients, such as phosphorus. In Japan, where dependence on imported fertilizers is high and global price fluctuations persist, using SS as fertilizer presents a sustainable alternative aligned with circular economy goals. This review analyzes Japan’s current efforts to repurpose SS, focusing on technological developments and key policy initiatives that promote safe and effective application. Selective phosphorus recovery technologies mitigate resource depletion, while holistic approaches, such as composting and carbonization, maximize sludge utilization for agricultural applications. Government-led initiatives, including public awareness campaigns, quality assurance standards and research support, have facilitated the adoption of sludge-based fertilizers. To contextualize Japan’s position, international trends, particularly in the EU, are also examined. These comparisons reveal both common strategies and areas for policy and technological advancement, especially regarding regulation of emerging contaminants. By integrating national case studies with global perspectives, the study offers insights into the economic, environmental, and social benefits of SS reuse, contributing to Japan’s goals of resource self-sufficiency and carbon neutrality, while also informing broader sustainable agriculture transitions worldwide. en-copyright= kn-copyright= en-aut-name=NguyenThu Huong en-aut-sei=Nguyen en-aut-mei=Thu Huong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraTaku en-aut-sei=Fujiwara en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamashitaHiromasa en-aut-sei=Yamashita en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TogawaHironori en-aut-sei=Togawa en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyakeHaruo en-aut-sei=Miyake en-aut-mei=Haruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GotoMasako en-aut-sei=Goto en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagareHideaki en-aut-sei=Nagare en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraMasato en-aut-sei=Nakamura en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OritateFumiko en-aut-sei=Oritate en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IharaHirotaka en-aut-sei=Ihara en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaedaMorihiro en-aut-sei=Maeda en-aut-mei=Morihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Graduate School of Engineering, Kyoto University kn-affil= affil-num=2 en-affil=Graduate School of Engineering, Kyoto University kn-affil= affil-num=3 en-affil=Water Supply and Sewerage Department, National Institute for Land and Infrastructure Management kn-affil= affil-num=4 en-affil=Water Supply and Sewerage Department, National Institute for Land and Infrastructure Management kn-affil= affil-num=5 en-affil=R & D Department, Japan Sewage Works Agency kn-affil= affil-num=6 en-affil=1St Research Department, Japan Institute of Wastewater Engineering and Technology kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Institute for Rural Engineering, NARO kn-affil= affil-num=9 en-affil=Institute for Rural Engineering, NARO kn-affil= affil-num=10 en-affil=Institute for Agro-Environmental Sciences, NARO kn-affil= affil-num=11 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Japan kn-keyword=Japan en-keyword=Sewage sludge kn-keyword=Sewage sludge en-keyword=Agriculture kn-keyword=Agriculture en-keyword=Sludge fertilizers kn-keyword=Sludge fertilizers en-keyword=Governmental initiatives kn-keyword=Governmental initiatives END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Primary tumour resection plus systemic therapy versus systemic therapy alone in metastatic breast cancer (JCOG1017, PRIM-BC): a randomised clinical trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Several prospective studies have evaluated the benefit of primary tumour resection (PTR) in de novo Stage IV breast cancer (BC) patients, but it remains controversial. We aimed to investigate whether PTR improves the survival of de novo stage IV BC patients.
Methods: De novo stage IV BC patients were enrolled in the first registration and received systemic therapies according to clinical subtypes. Patients without progression after primary systemic therapy for 3 months were randomly assigned 1:1 to systemic therapy alone (arm A) or PTR plus systemic therapy (arm B). The primary endpoint was overall survival (OS), and the secondary endpoints included local relapse-free survival (LRFS).
Results: Five hundred seventy patients were enrolled between May 5, 2011, and May 31, 2018. Of these, 407 were randomised to arm A (N = 205) or arm B (N = 202). The median follow-up time of all randomised patients was 60 months. The difference in OS was not statistically significant (HR 0.86 90% CI 0.69–1.07, one-sided p = 0.13). Median OS was 69 months (arm A) and 75 months (arm B). In the subgroup analysis, PTR was associated with improved OS in pre-menopausal patients, or those with single-organ metastasis. LRFS in arm B was significantly longer than that in arm A (median LRFS 20 vs. 63 months: HR 0.42, 95% CI 0.33–0.53, p < 0.0001). There were no treatment-related deaths.
Conclusions: PTR did not prolong OS. However, it improved local control and might benefit a subset of patients, such as those with premenopausal status or with single-organ metastasis. It also improved local relapse-free survival (LRFS), which is a clinically meaningful outcome in trials of systemic therapy.
Clinical trial registration: UMIN Clinical Trials Registry (UMIN000005586); Japan Registry of Clinical Trials (jRCTs031180151). en-copyright= kn-copyright= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AogiKenjiro en-aut-sei=Aogi en-aut-mei=Kenjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YanagidaYasuhiro en-aut-sei=Yanagida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuneizumiMichiko en-aut-sei=Tsuneizumi en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoNaohito en-aut-sei=Yamamoto en-aut-mei=Naohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoHiroshi en-aut-sei=Matsumoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SutoAkihiko en-aut-sei=Suto en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WatanabeKenichi en-aut-sei=Watanabe en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaraoMichiko en-aut-sei=Harao en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KanbayashiChizuko en-aut-sei=Kanbayashi en-aut-mei=Chizuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ItohMitsuya en-aut-sei=Itoh en-aut-mei=Mitsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KadoyaTakayuki en-aut-sei=Kadoya en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AnanKeisei en-aut-sei=Anan en-aut-mei=Keisei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaShigeto en-aut-sei=Maeda en-aut-mei=Shigeto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SasakiKeita en-aut-sei=Sasaki en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OgawaGakuto en-aut-sei=Ogawa en-aut-mei=Gakuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SajiShigehira en-aut-sei=Saji en-aut-mei=Shigehira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FukudaHaruhiko en-aut-sei=Fukuda en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IwataHiroji en-aut-sei=Iwata en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Okayama University Hospital kn-affil= affil-num=2 en-affil=Cancer Institute Hospital kn-affil= affil-num=3 en-affil=National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Shizuoka General Hospital kn-affil= affil-num=5 en-affil=Gunma Prefectural Cancer Center kn-affil= affil-num=6 en-affil=Chiba Prefectural Cancer Center kn-affil= affil-num=7 en-affil=Saitama Prefectural Cancer Center kn-affil= affil-num=8 en-affil=National Cancer Center Hospital kn-affil= affil-num=9 en-affil=Hokkaido Cancer Center kn-affil= affil-num=10 en-affil=Jichi Medical University Hospital kn-affil= affil-num=11 en-affil=Niigata Prefectural Cancer Center kn-affil= affil-num=12 en-affil=Hiroshima City Hiroshima Citizen’s Hospital kn-affil= affil-num=13 en-affil=Hiroshima University Hospital kn-affil= affil-num=14 en-affil=Kitakyushu Municipal Medical Center kn-affil= affil-num=15 en-affil=Nagasaki Municipal Medical Center kn-affil= affil-num=16 en-affil=National Cancer Center Hospital kn-affil= affil-num=17 en-affil=National Cancer Center Hospital kn-affil= affil-num=18 en-affil=Fukushima Medical University kn-affil= affil-num=19 en-affil=National Cancer Center Hospital kn-affil= affil-num=20 en-affil=Aichi Cancer Center Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=1 article-no= start-page=e261 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alcohol consumption, multiple Lugol‐voiding lesions, and field cancerization en-subtitle= kn-subtitle= en-abstract= kn-abstract=The development of multiple squamous cell carcinomas (SCC) in the upper aerodigestive tract, which includes the oral cavity, pharynx, larynx, and esophagus, is explained by field cancerization and is associated with alcohol consumption and cigarette smoking. We reviewed the association between alcohol consumption, multiple Lugol-voiding lesions, and field cancerization, mainly based on the Japan Esophageal Cohort study. The Japan Esophageal Cohort study is a prospective cohort study that enrolled patients with esophageal SCC after endoscopic resection. Enrolled patients received surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months. The Japan Esophageal Cohort study showed that esophageal SCC and head and neck SCC that developed after endoscopic resection for esophageal SCC were associated with genetic polymorphisms related to alcohol metabolism. They were also associated with Lugol-voiding lesions grade in the background esophageal mucosa, the score of the health risk appraisal model for predicting the risk of esophageal SCC, macrocytosis, and score on alcohol use disorders identification test. The standardized incidence ratio of head and neck SCC in patients with esophageal SCC after endoscopic resection was extremely high compared to the general population. Drinking and smoking cessation is strongly recommended to reduce the risk of metachronous esophageal SCC after treatment of esophageal SCC. Risk factors for field cancerization provide opportunities for early diagnosis and minimally invasive treatment. Lifestyle guidance of alcohol consumption and cigarette smoking for esophageal precancerous conditions, which are endoscopically visualized as multiple Lugol-voiding lesions, may play a pivotal role in decreasing the incidence and mortality of esophageal SCC. en-copyright= kn-copyright= en-aut-name=KatadaChikatoshi en-aut-sei=Katada en-aut-mei=Chikatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokoyamaTetsuji en-aut-sei=Yokoyama en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanoTomonori en-aut-sei=Yano en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiHaruhisa en-aut-sei=Suzuki en-aut-mei=Haruhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FurueYasuaki en-aut-sei=Furue en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoKeiko en-aut-sei=Yamamoto en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DoyamaHisashi en-aut-sei=Doyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoikeTomoyuki en-aut-sei=Koike en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TamaokiMasashi en-aut-sei=Tamaoki en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawataNoboru en-aut-sei=Kawata en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HiraoMotohiro en-aut-sei=Hirao en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OgataTakashi en-aut-sei=Ogata en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatagiriAtsushi en-aut-sei=Katagiri en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamanouchiTakenori en-aut-sei=Yamanouchi en-aut-mei=Takenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KiyokawaHirofumi en-aut-sei=Kiyokawa en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KawakuboHirofumi en-aut-sei=Kawakubo en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KonnoMaki en-aut-sei=Konno en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YokoyamaAkira en-aut-sei=Yokoyama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhashiShinya en-aut-sei=Ohashi en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KondoYuki en-aut-sei=Kondo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KishimotoYo en-aut-sei=Kishimoto en-aut-mei=Yo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KanoKoichi en-aut-sei=Kano en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MureKanae en-aut-sei=Mure en-aut-mei=Kanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=HayashiRyuichi en-aut-sei=Hayashi en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IshikawaHideki en-aut-sei=Ishikawa en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=YokoyamaAkira en-aut-sei=Yokoyama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MutoManabu en-aut-sei=Muto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=2 en-affil=Department of Health and Promotion, National Institute of Public Health kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East kn-affil= affil-num=4 en-affil=Endoscopy Division, National Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=6 en-affil=Division of Endoscopy, Hokkaido University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Ishikawa Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=10 en-affil=Division of Endoscopy, Shizuoka Cancer Center kn-affil= affil-num=11 en-affil=Department of Surgery, National Hospital Organization Osaka National Hospital kn-affil= affil-num=12 en-affil=Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Gastroenterology, Kanagawa Cancer Center kn-affil= affil-num=14 en-affil=Department of Medicine, Division of Gastroenterology, Showa University Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Kumamoto Regional Medical Center kn-affil= affil-num=16 en-affil=Division of Gastroenterology, Department of Internal Medicine, St. Marianna University School of Medicine kn-affil= affil-num=17 en-affil=Department of Surgery, Kawasaki Municipal Kawasaki Hospital kn-affil= affil-num=18 en-affil=Department of Gastroenterology, Tochigi Cancer Center kn-affil= affil-num=19 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=20 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=21 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=22 en-affil=Department of Otolaryngology-Head and Neck Surgery, Kyoto University Hospital kn-affil= affil-num=23 en-affil=Department of Otorhinolaryngology-Head and Neck Surgery, Kitasato University School of Medicine kn-affil= affil-num=24 en-affil=Department of Public Health, Wakayama Medical University School of Medicine kn-affil= affil-num=25 en-affil=Department of Head and Neck Surgery, National Cancer Center Hospital East kn-affil= affil-num=26 en-affil=Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine kn-affil= affil-num=27 en-affil=Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center kn-affil= affil-num=28 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= en-keyword=alcohol kn-keyword=alcohol en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=field cancerization kn-keyword=field cancerization en-keyword=head and neck cancer kn-keyword=head and neck cancer en-keyword=JEC study kn-keyword=JEC study END start-ver=1.4 cd-journal=joma no-vol=638 cd-vols= no-issue=8049 article-no= start-page=225 end-page=236 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immune evasion through mitochondrial transfer in the tumour microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T cell attack1. For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumour immune responses2,3,4. However, detailed mechanisms of such processes remain unclear. Here we analyse clinical specimens and identify mitochondrial DNA (mtDNA) mutations in TILs that are shared with cancer cells. Moreover, mitochondria with mtDNA mutations from cancer cells are able to transfer to TILs. Typically, mitochondria in TILs readily undergo mitophagy through reactive oxygen species. However, mitochondria transferred from cancer cells do not undergo mitophagy, which we find is due to mitophagy-inhibitory molecules. These molecules attach to mitochondria and together are transferred to TILs, which results in homoplasmic replacement. T cells that acquire mtDNA mutations from cancer cells exhibit metabolic abnormalities and senescence, with defects in effector functions and memory formation. This in turn leads to impaired antitumour immunity both in vitro and in vivo. Accordingly, the presence of an mtDNA mutation in tumour tissue is a poor prognostic factor for immune checkpoint inhibitors in patients with melanoma or non-small-cell lung cancer. These findings reveal a previously unknown mechanism of cancer immune evasion through mitochondrial transfer and can contribute to the development of future cancer immunotherapies. en-copyright= kn-copyright= en-aut-name=IkedaHideki en-aut-sei=Ikeda en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaseKatsushige en-aut-sei=Kawase en-aut-mei=Katsushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiTatsuya en-aut-sei=Nishi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeTomofumi en-aut-sei=Watanabe en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakenagaKeizo en-aut-sei=Takenaga en-aut-mei=Keizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AkiSho en-aut-sei=Aki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=LinJason en-aut-sei=Lin en-aut-mei=Jason kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawashimaShusuke en-aut-sei=Kawashima en-aut-mei=Shusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SuzukiShinichiro en-aut-sei=Suzuki en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MakinoshimaHideki en-aut-sei=Makinoshima en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ItamiMakiko en-aut-sei=Itami en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NakamuraYuki en-aut-sei=Nakamura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TatsumiYasutoshi en-aut-sei=Tatsumi en-aut-mei=Yasutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SuenagaYusuke en-aut-sei=Suenaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MorinagaTakao en-aut-sei=Morinaga en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=Honobe-TabuchiAkiko en-aut-sei=Honobe-Tabuchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=OhnumaTakehiro en-aut-sei=Ohnuma en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KawamuraTatsuyoshi en-aut-sei=Kawamura en-aut-mei=Tatsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=UmedaYoshiyasu en-aut-sei=Umeda en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=NakamuraYasuhiro en-aut-sei=Nakamura en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KiniwaYukiko en-aut-sei=Kiniwa en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=HayashiHidetoshi en-aut-sei=Hayashi en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=IkedaJun-ichiro en-aut-sei=Ikeda en-aut-mei=Jun-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=HanazawaToyoyuki en-aut-sei=Hanazawa en-aut-mei=Toyoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=ManoHiroyuki en-aut-sei=Mano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=SuzukiTakuji en-aut-sei=Suzuki en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=OsawaTsuyoshi en-aut-sei=Osawa en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=KawazuMasahito en-aut-sei=Kawazu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= affil-num=1 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=2 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=3 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Division of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute kn-affil= affil-num=6 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=7 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Division of Nutriomics and Oncology, RCAST, The University of Tokyo kn-affil= affil-num=9 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=10 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan Department of Dermatology, Graduate School of Medicine, Chiba University kn-affil= affil-num=11 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Tsuruoka Metabolomics Laboratory, National Cancer Center kn-affil= affil-num=15 en-affil=Department of Surgical Pathology, Chiba Cancer Center kn-affil= affil-num=16 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=17 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=18 en-affil=Laboratory of Evolutionary Oncology, Chiba Cancer Center Research Institute kn-affil= affil-num=19 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=20 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=21 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=22 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=23 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=24 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=25 en-affil=Department of Dermatology, Shinshu University School of Medicine kn-affil= affil-num=26 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=27 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=28 en-affil=Department of Diagnostic Pathology, Graduate School of Medicine, Chiba University kn-affil= affil-num=29 en-affil=Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine kn-affil= affil-num=30 en-affil=Department of General Thoracic Surgery and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=31 en-affil=Division of Cellular Signalling, National Cancer Center Research Institute kn-affil= affil-num=32 en-affil=Department of Respirology, Graduate School of Medicine, Chiba University kn-affil= affil-num=33 en-affil=Division of Nutriomics and Oncology, RCAST, The University of Tokyo kn-affil= affil-num=34 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=35 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=6 article-no= start-page=1008 end-page=1016 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240422 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High risk of multiple gastric cancers in Japanese individuals with Lynch syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim: Lynch syndrome (LS) is a dominantly inherited syndrome characterized by an increased risk for LS associated tumors such as colorectal cancer (CRC) and gastric cancer (GC). However, the clinical benefit of surveillance for GC remains unclear while it has already been recommended for CRC. This study aimed to elucidate the clinical features of GC in Japanese individuals with LS, and the risk of developing multiple GCs to build regional-tailored surveillance programs in LS patients with GC.
Methods: Data on Japanese individuals with LS were retrospectively collected from a single institution. The clinical features of GC, including the cumulative risk of multiple GCs, were analyzed.
Results: Among 96 individuals with LS (MLH1/MSH2/MSH6, 75:20:1), 32 GC lesions were detected in 15 individuals with LS (male/female, 11:4). The median age at initial GC diagnosis was 52.7 y (range: 28–71). Histological examination revealed a predominance of intestinal type (19/24: 87.5%). Moreover, the majority of the GC lesions (82%) were determined to have high-frequency of microsatellite instability. The cumulative risk of individuals with LS developing GC at 70 y was 31.3% (MLH1 36.1%, MSH2 18.0%). Notably, the cumulative risk of individuals with LS developing metachronous and/or synchronous GCs at 0, 10 and 20 y after initial diagnosis of GC was 26.7%, 40.7%, and 59.4%, respectively.
Conclusion: Due to a higher risk of developing multiple GCs, intensive surveillance might be especially recommended for Japanese individuals with LS associated initial GC. en-copyright= kn-copyright= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=van SchaikThijs A. en-aut-sei=van Schaik en-aut-mei=Thijs A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AokiHideki en-aut-sei=Aoki en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoYumiko en-aut-sei=Sato en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaniguchiFumitaka en-aut-sei=Taniguchi en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuganoKokichi en-aut-sei=Sugano en-aut-mei=Kokichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AkagiKiwamu en-aut-sei=Akagi en-aut-mei=Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshidaHideyuki en-aut-sei=Ishida en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakayaKohji en-aut-sei=Tanakaya en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School kn-affil= affil-num=3 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=4 en-affil=Department of Pathology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=5 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Genetic Medicine, Kyoundo Hospital, SSasaki Foundation kn-affil= affil-num=8 en-affil=Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center kn-affil= affil-num=9 en-affil=Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=10 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= en-keyword=cumulative risk kn-keyword=cumulative risk en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=Japanese individuals kn-keyword=Japanese individuals en-keyword=Lynch syndrome kn-keyword=Lynch syndrome en-keyword=multiple gastric cancers kn-keyword=multiple gastric cancers END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=5 article-no= start-page=271 end-page=277 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240329 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Japan MSA registry: A multicenter cohort study of multiple system atrophy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure and various motor symptoms. While MSA-C (cerebellar type) predominates in East Asia, MSA-P (parkinsonian type) predominates in Europe and North America. This nationwide patient registry aimed to (1) conduct a prospective natural history study of MSA in Japan, (2) facilitate patient recruitment for clinical trials, and (3) deposit bioresources and clinical information in a biobank.
Methods: Thirteen institutions participated in this study. Clinical information was obtained by neurologists from the patients visiting the hospital every 12 months to assess the UMSARS Part 2 scores and by telephone interviews by nurses every 6 months to assess UMSARS Part 1 scores and to determine whether clinical events had occurred.
Results: Demographic data from 329 MSA patients (216 MSA-C and 113 MSA-P) were analyzed. The mean age at symptom onset was 58.2 years (standard deviation, 8.9); the mean duration of symptoms at enrollment was 3.5 years (standard deviation, 2.2). The mean 12-month changes in the UMSARS Part 1 and Part 2 scores were 7.9 (standard deviation, 5.6) and 6.4 (standard deviation, 5.9), respectively. The patient registry proved useful in recruiting participants for clinical trials, including those with gene variants. Clinical information and biospecimens were deposited in a biobank.
Discussion: The study highlighted the importance of telephone interviews in minimizing drop-out rates in natural history studies and demonstrated similar MSA progression rates across populations. The deposited bioresources are available to researchers upon request, aiming to contribute to future MSA researches. en-copyright= kn-copyright= en-aut-name=ChikadaAyaka en-aut-sei=Chikada en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OrimoKenta en-aut-sei=Orimo en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MizusawaHidehiro en-aut-sei=Mizusawa en-aut-mei=Hidehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakahashiYuji en-aut-sei=Takahashi en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatsunoMasahisa en-aut-sei=Katsuno en-aut-mei=Masahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaraKazuhiro en-aut-sei=Hara en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OnoderaOsamu en-aut-sei=Onodera en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IshiharaTomohiko en-aut-sei=Ishihara en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TadaMasayoshi en-aut-sei=Tada en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KuwabaraSatoshi en-aut-sei=Kuwabara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SugiyamaAtsuhiko en-aut-sei=Sugiyama en-aut-mei=Atsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamanakaYoshitaka en-aut-sei=Yamanaka en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakahashiRyosuke en-aut-sei=Takahashi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SawamotoNobukatsu en-aut-sei=Sawamoto en-aut-mei=Nobukatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SakatoYusuke en-aut-sei=Sakato en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IshimotoTomoyuki en-aut-sei=Ishimoto en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HanajimaRitsuko en-aut-sei=Hanajima en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=WatanabeYasuhiro en-aut-sei=Watanabe en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TakigawaHiroshi en-aut-sei=Takigawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=AdachiTadashi en-aut-sei=Adachi en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TakashimaHiroshi en-aut-sei=Takashima en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=HigashiKeiko en-aut-sei=Higashi en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KiraJunichi en-aut-sei=Kira en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=YabeIchiro en-aut-sei=Yabe en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=MatsushimaMasaaki en-aut-sei=Matsushima en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=OgataKatsuhisa en-aut-sei=Ogata en-aut-mei=Katsuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=IshikawaKinya en-aut-sei=Ishikawa en-aut-mei=Kinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=NishidaYoichiro en-aut-sei=Nishida en-aut-mei=Yoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=IshiguroTaro en-aut-sei=Ishiguro en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=OzakiKokoro en-aut-sei=Ozaki en-aut-mei=Kokoro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=NagataTetsuya en-aut-sei=Nagata en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Neurology, Nagoya University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Neurology, Nagoya University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=12 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=13 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=15 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=16 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=17 en-affil=Department of Neurology, Kyoto University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Human Health Sciences, Kyoto University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Neurology, Kyoto University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Neurology, Kyoto University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University kn-affil= affil-num=22 en-affil=Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University kn-affil= affil-num=23 en-affil=Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University kn-affil= affil-num=24 en-affil=Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University kn-affil= affil-num=25 en-affil=Department of Neurology, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=26 en-affil=Department of Neurology, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=27 en-affil=Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=28 en-affil=Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=29 en-affil=Department of Neurology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=30 en-affil=Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=31 en-affil=Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=32 en-affil=Department of Neurology, Higashi-Saitama National Hospital kn-affil= affil-num=33 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=34 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=35 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=36 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=37 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=38 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=multicenter cohort study kn-keyword=multicenter cohort study en-keyword=multiple system atrophy kn-keyword=multiple system atrophy en-keyword=natural history kn-keyword=natural history en-keyword=patient registry kn-keyword=patient registry END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=12 article-no= start-page=613 end-page=621 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240718 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association study of GBA1 variants with MSA based on comprehensive sequence analysis -Pitfalls in short-read sequence analysis depending on the human reference genome- en-subtitle= kn-subtitle= en-abstract= kn-abstract=Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by various combinations of autonomic failure, parkinsonism, and cerebellar ataxia. To elucidate variants associated with MSA, we have been conducting short-read-based whole-genome sequence analysis. In the process of the association studies, we initially focused on GBA1, a previously proposed susceptibility gene for MSA, to evaluate whether GBA1 variants can be efficiently identified despite its extraordinarily high homology with its pseudogene, GBA1LP. To accomplish this, we conducted a short-read whole-genome sequence analysis with alignment to GRCh38 as well as Sanger sequence analysis and compared the results. We identified five variants with inconsistencies between the two pipelines, of which three variants (p.L483P, p.A495P–p.V499V, p.L483_M489delinsW) were the results of misalignment due to minor alleles in GBA1P1 registered in GRCh38. The miscalling events in these variants were resolved by alignment to GRCh37 as the reference genome, where the major alleles are registered. In addition, a structural variant was not properly identified either by short-read or by Sanger sequence analyses. Having accomplished correct variant calling, we identified three variants pathogenic for Gaucher disease (p.S310G, p.L483P, and p.L483_M489delinsW). Of these variants, the allele frequency of p.L483P (0.003) in the MSA cases was higher than that (0.0011) in controls. The meta-analysis incorporating a previous report demonstrated a significant association of p.L483P with MSA with an odds ratio of 2.85 (95% CI; 1.05 – 7.76, p = 0.0400). en-copyright= kn-copyright= en-aut-name=OrimoKenta en-aut-sei=Orimo en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaMasaki en-aut-sei=Tanaka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NomotoJunko en-aut-sei=Nomoto en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OmaeYosuke en-aut-sei=Omae en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaiYosuke en-aut-sei=Kawai en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TokunagaKatsushi en-aut-sei=Tokunaga en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NCBN Controls WGS Consortium en-aut-sei=NCBN Controls WGS Consortium en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=5 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Genome Medical Science Project, National Center for Global Health and Medicine kn-affil= affil-num=8 en-affil=Genome Medical Science Project, National Center for Global Health and Medicine kn-affil= affil-num=9 en-affil=Genome Medical Science Project, National Center for Global Health and Medicine kn-affil= affil-num=10 en-affil= kn-affil= affil-num=11 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=12 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=3 article-no= start-page=79 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association of the expression of 5‑FU biomarkers with aging and prognosis in elderly patients with lung cancer treated with S‑1 adjuvant chemotherapy: Follow‑up results of the Setouchi Lung Cancer Group Study 1201 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Managing elderly patients presents several challenges because of age‑related declines; however, age should not be the sole determinant for adjuvant treatment decisions in patients with non‑small cell lung cancer (NSCLC). Moreover, age may affect the expression of 5‑fluorouracil (5‑FU) biomarkers. The present study assessed: i) The effect of age on the expression levels of 5‑FU biomarkers by analyzing a public database; and ii) the ability of these biomarkers to predict clinical outcomes in elderly patients with NSCLC who underwent complete resection in the Setouchi Lung Cancer Group Study 1201 (SCLG1201) followed by S‑1 adjuvant chemotherapy. Changes in gene expression levels across age groups were assessed by analyzing The Cancer Genome Atlas (TCGA) database. The expression of 5‑FU biomarkers, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, epidermal growth factor receptor (EGFR) and excision repair cross‑complementation group 1 (ERCC1), were assessed via quantitative reverse‑transcription PCR assays in 89 elderly patients (≥75 years) with NSCLC who received adjuvant chemotherapy with oral fluoropyrimidine prodrug S‑1 in the SLCG1201 trial. TCGA database analysis (n=955) showed that TS expression decreased significantly with aging, especially in the age group ≥75. In the SCLG1201 trial, univariate analysis revealed that EGFR upregulation and TS downregulation were correlated with favorable recurrence‑free survival (RFS) and overall survival (OS), respectively. Multivariate analysis demonstrated that pathological stage was an independent prognostic factor for both RFS and OS. EGFR mutations were associated with upregulation of DPD and EGFR, and downregulation of TS and ERCC1. In conclusion, although pathological stage is an independent prognostic factor for survival, EGFR upregulation and TS downregulation may be a greater predictor of clinical outcomes in elderly patients with NSCLC treated with S‑1 adjuvant chemotherapy. The age‑related decrease in TS expression supports the potential benefit of 5‑FU therapies in elderly patients. Nonetheless, further research is warranted to validate these results. en-copyright= kn-copyright= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkumuraNorihito en-aut-sei=Okumura en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiHiroyuki en-aut-sei=Suzuki en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakataMasao en-aut-sei=Nakata en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GembaKenicehi en-aut-sei=Gemba en-aut-mei=Kenicehi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SanoIsao en-aut-sei=Sano en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujinagaTakuji en-aut-sei=Fujinaga en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KataokaMasafumi en-aut-sei=Kataoka en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TerasakiYasuhiro en-aut-sei=Terasaki en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KataokaKazuhiko en-aut-sei=Kataoka en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KosakaShinji en-aut-sei=Kosaka en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=InokawaHidetoshi en-aut-sei=Inokawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakamuraHiroshige en-aut-sei=Nakamura en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamashitaYoshinori en-aut-sei=Yamashita en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakahashiYuta en-aut-sei=Takahashi en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TorigoeHidejiro en-aut-sei=Torigoe en-aut-mei=Hidejiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=SatoHiroki en-aut-sei=Sato en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=MoritaSatoshi en-aut-sei=Morita en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=MatsuoKeitaro en-aut-sei=Matsuo en-aut-mei=Keitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=SakamotoJunichi en-aut-sei=Sakamoto en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=DateHiroshi en-aut-sei=Date en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Chest Surgery, Fukushima Medical University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Hiroshima 720‑0001, Japan; 8Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, National Hospital Organization Nagara Medical Center kn-affil= affil-num=10 en-affil=Department of Surgery and Respiratory Center, Okayama Saiseikai General Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Surgery, Saga Medical Center Koseikan kn-affil= affil-num=12 en-affil=Department of Medical Oncology and Respiratory Medicine, Okayama Rosai Hospital kn-affil= affil-num=13 en-affil=Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=14 en-affil=Department of Thoracic Surgery, Shimane Prefectural Central Hospital kn-affil= affil-num=15 en-affil=Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=16 en-affil=Department of Thoracic Surgery, National Hospital Organization Yamaguchi‑Ube Medical Center kn-affil= affil-num=17 en-affil=Department of Thoracic Surgery, Shimonoseki City Hospital kn-affil= affil-num=18 en-affil=Division of General Thoracic Surgery, Tottori University Hospital kn-affil= affil-num=19 en-affil=Department of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center kn-affil= affil-num=20 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=22 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=23 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=24 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=25 en-affil=Department of Thoracic Oncology, Kansai Medical University Hospital kn-affil= affil-num=26 en-affil=Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine kn-affil= affil-num=27 en-affil=Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute kn-affil= affil-num=28 en-affil=Tokai Central Hospital kn-affil= affil-num=29 en-affil=Department of Thoracic Surgery, Kyoto University Hospital kn-affil= affil-num=30 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=non‑small cell lung cancer kn-keyword=non‑small cell lung cancer en-keyword=elderly patients kn-keyword=elderly patients en-keyword=adjuvant chemotherapy kn-keyword=adjuvant chemotherapy en-keyword=S‑1 kn-keyword=S‑1 en-keyword=EGFR kn-keyword=EGFR en-keyword=TP kn-keyword=TP en-keyword=TS kn-keyword=TS en-keyword=OPRT kn-keyword=OPRT en-keyword=ERCC1 kn-keyword=ERCC1 en-keyword=DPD kn-keyword=DPD END start-ver=1.4 cd-journal=joma no-vol=150 cd-vols= no-issue=1 article-no= start-page=19 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biallelic variants in DNAJC7 cause familial amyotrophic lateral sclerosis with the TDP-43 pathology en-subtitle= kn-subtitle= en-abstract= kn-abstract=Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. ALS pathology primarily involves the failure of protein quality control mechanisms, leading to the accumulation of misfolded proteins, particularly TAR DNA-binding protein 43 (TDP-43). TDP-43 aggregation is a central pathological feature of ALS. Maintaining protein homeostasis is critical and facilitated by heat shock proteins (HSPs), particularly the HSP40 family, which includes co-chaperones such as DNAJC7. Here, we report a family with three siblings affected by ALS who carry a homozygous c.518dupC frameshift variant in DNAJC7, a member of the HSP40 family. All three patients exhibited progressive muscle weakness, limb atrophy, bulbar palsy, and respiratory failure. Pathological examination revealed degeneration of both upper and lower motor neurons, with phosphorylated TDP-43-positive neuronal cytoplasmic inclusions in the frontal and temporal cortices. Immunoblot analysis were consistent with a type B pattern of phosphorylated TDP-43 in the precentral gyrus. Immunohistochemistry and RNA sequencing analyses demonstrated a substantial reduction in DNAJC7 expression at both the protein and RNA levels in affected brain regions. In a TDP-43 cell model, DNAJC7 knockdown impaired the disassembly of TDP-43 following arsenite-induced stress, whereas DNAJC7 overexpression suppressed the assembly and promoted the disassembly of arsenite-induced TDP-43 condensates. Furthermore, in a zebrafish ALS model, dnajc7 knockdown resulted in increased TDP-43 aggregation in motor neurons and reduced survival. To the best of our knowledge, this study provides the first evidence linking biallelic loss-of-function variants in DNAJC7 to familial ALS with TDP-43 pathology. en-copyright= kn-copyright= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokotaOsamu en-aut-sei=Yokota en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OusakaDaiki en-aut-sei=Ousaka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SunHongming en-aut-sei=Sun en-aut-mei=Hongming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiTakashi en-aut-sei=Haraguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Ota-ElliottRicardo Satoshi en-aut-sei=Ota-Elliott en-aut-mei=Ricardo Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuokaChika en-aut-sei=Matsuoka en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawanoTomohito en-aut-sei=Kawano en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Nakashima-YasudaHanae en-aut-sei=Nakashima-Yasuda en-aut-mei=Hanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukuiYusuke en-aut-sei=Fukui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakanoYumiko en-aut-sei=Nakano en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HasegawaMasato en-aut-sei=Hasegawa en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HosonoYasuyuki en-aut-sei=Hosono en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TeradaSeishi en-aut-sei=Terada en-aut-mei=Seishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurology, National Hospital Organisation Minami-Okayama Medical Centre kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Psychiatry, Zikei Hospital kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Brain and Neurosciences, Tokyo Metropolitan Institute of Medical Science kn-affil= affil-num=14 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Amyotrophic lateral sclerosis kn-keyword=Amyotrophic lateral sclerosis en-keyword=Heat shock protein kn-keyword=Heat shock protein en-keyword=DNAJC7 kn-keyword=DNAJC7 en-keyword=TDP-43 kn-keyword=TDP-43 en-keyword=Live-cell imaging kn-keyword=Live-cell imaging en-keyword=Zebrafish disease model kn-keyword=Zebrafish disease model END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=11 article-no= start-page=348 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Coronal Cementum and Reduced Enamel Epithelium on Occlusal Surface of Impacted Wisdom Tooth in a Human en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: There is only limited research on the coronal cementum of a tooth, and the mechanisms of its forming process are not well-defined. This report presents a coronal cementum on the occlusal surfaces of enamel in an impacted wisdom tooth in a human, which is not nearly the cervical portion. Materials and Methods: The tooth (Tooth #1) was derived from a 46-year-old female. Histological analysis, including hematoxylin and eosin (HE) and toluidine blue (TB) staining, and Scanning Electron Microscopy and Energy Dispersive X-ray Spectrometer (SEM-EDS) analysis of the extracted tooth were conducted. Radiographic examination showed that Tooth #1 was horizontally impacted in the maxilla and had the apex of a single root placed between the buccal and palatal roots of Tooth #2. Results: Coronal cementum was distributed widely on the enamel, and reduced enamel epithelium was also found with enamel matrix proteins histologically. The formation of acellular cementum was observed to be more predominant than that of the cellular cementum in Tooth #1. SEM showed that the occlusal cementum connected directly with enamel. Calcium mapping revealed an almost similar occlusal cementum and enamel. In addition, the spectrum of elements in coronal cementum resembled the primary cementum according to SEM-EDS. Discussion: Thus, coronal cementogenesis in impacted human teeth might be related to the existence of reduced enamel epithelium. en-copyright= kn-copyright= en-aut-name=HorieNaohiro en-aut-sei=Horie en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MurataMasaru en-aut-sei=Murata en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MinamidaYasuhito en-aut-sei=Minamida en-aut-mei=Yasuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagayasuHiroki en-aut-sei=Nagayasu en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimoTsuyoshi en-aut-sei=Shimo en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkazawaToshiyuki en-aut-sei=Akazawa en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujigiwaHidetsugu en-aut-sei=Tsujigiwa en-aut-mei=Hidetsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaikelYoussef en-aut-sei=Haikel en-aut-mei=Youssef kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=2 en-affil=Division of Regenerative Medicine, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=3 en-affil=Division of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=4 en-affil=Division of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=5 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=6 en-affil=Industrial Technology and Environment Research Development, Hokkaido Research Organization kn-affil= affil-num=7 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= affil-num=8 en-affil=Department of Biomaterials and Bioengineering, Institut National de la Santé et de la Recherche médicale Unité Mixte de Recherche (INSERM UMR) _S 1121, University of Strasbourg kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=coronal cementum kn-keyword=coronal cementum en-keyword=human kn-keyword=human en-keyword=reduced epithelium kn-keyword=reduced epithelium en-keyword=impacted tooth kn-keyword=impacted tooth END start-ver=1.4 cd-journal=joma no-vol=122 cd-vols= no-issue=32 article-no= start-page=e2501933122 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250805 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural insights into a citrate transporter that mediates aluminum tolerance in barley en-subtitle= kn-subtitle= en-abstract= kn-abstract=HvAACT1 is a major aluminum (Al)-tolerance gene in barley, encoding a citrate transporter that belongs to the multidrug and toxic compound extrusion (MATE) family. This transporter facilitates citrate secretion from the roots, thereby detoxifying external Al ions—a major constraint of crop production on acidic soils. In this study, we present the outward-facing crystal structure of HvAACT1, providing insights into a citrate transport mechanism. The putative citrate binding site consists of three basic residues—K126 in transmembrane helix 2 (TM2), R358 in TM7, and R535 in TM12—creating substantial positive charges in the C-lobe cavity. Proton coupling for substrate transport may involve two pairs of aspartate residues in the N-lobe cavity, one of which corresponds to the essential Asp pair found in prokaryotic H+-coupled MATE transporters belonging to the DinF subfamily. Structural coupling between proton uptake in the N-lobe and citrate extrusion in the C-lobe can be enabled by an extensive, unique hydrogen-bonding network at the extracellular half of the N-lobe. Mutation-based functional analysis, structural comparisons, molecular dynamics simulation, and phylogenic analysis suggest an evolutionary link between citrate MATE transporters and the DinF MATE subfamily. Our findings provide a solid structural basis for citrate transport by HvAACT1 in barley and contribute to a broader understanding of citrate transporter structures in other plant species. en-copyright= kn-copyright= en-aut-name=Nguyen ThaoTran en-aut-sei=Nguyen Thao en-aut-mei=Tran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Mitani-UenoNamiki en-aut-sei=Mitani-Ueno en-aut-mei=Namiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UranoRyo en-aut-sei=Urano en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitohYasunori en-aut-sei=Saitoh en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangPeitong en-aut-sei=Wang en-aut-mei=Peitong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamajiNaoki en-aut-sei=Yamaji en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShinodaWataru en-aut-sei=Shinoda en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaJian Feng en-aut-sei=Ma en-aut-mei=Jian Feng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugaMichihiro en-aut-sei=Suga en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Division of Superconducting and Functional Materials, Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=5 en-affil=Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=8 en-affil=Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=9 en-affil=Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=10 en-affil=Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= en-keyword=barley kn-keyword=barley en-keyword=aluminum resistance kn-keyword=aluminum resistance en-keyword=membrane protein structure kn-keyword=membrane protein structure en-keyword=citrate transporter kn-keyword=citrate transporter en-keyword=MATE transporter kn-keyword=MATE transporter END start-ver=1.4 cd-journal=joma no-vol=38 cd-vols= no-issue=9 article-no= start-page=e70105 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250724 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ultrahigh‐Field MR‐Compatible Mechanical Tactile Stimulator for Investigating Somatosensory Processing in Small‐Bodied Animals en-subtitle= kn-subtitle= en-abstract= kn-abstract=Common marmosets (Callithrix jacchus), small-bodied New World primates that share similar sensory processing pathways with human beings, have gained great interests. Their small body size allows imaging of brain activity with high spatial resolution and on a whole-brain scale using ultrahigh-field (UHF) magnetic resonance imaging (MRI) scanners. However, the strong magnetic field and the small size of the hand and forearm pose challenges in delivering tactile stimulation during fMRI experiments. In the present study, we developed an MR-compatible tactile dual-point stimulator to provide high-precision mechanical stimulation for exploring somatosensory processing in small-bodied animals. The study population consisted of a water phantom and three male common marmosets. Cerebral blood volume (CBV) weighted fMRI data were obtained with a gradient echo (GE), echo-planar imaging (EPI) sequence at 7T scanner. The output performance of the device was tested by a pressure sensor. The MR compatibility of the device was verified by measuring the temporal signal-to-noise ratio (tSNR) of a water phantom. To test the effectiveness of tactile stimulation, we conducted block designed tactile stimulation experiments on marmosets. A one-way repeated measures ANOVA was conducted for comparing the tSNR results. We performed one-sample t-tests to investigate the negative response of the forearm and hand stimulation with a threshold of t > 1.96 (p < 0.05). Performance tests revealed that mechanical stimulation (averaged force: 31.69 g) was applied with a delay of 12 ms. Phantom experiments confirmed that there was no significant difference in the tSNR among three (10 Hz, 1 Hz, and no-stimulus) conditions (F (2, 798) = 0.71, p = 0.49). The CBV activity results showed that the stimulator successfully elicited hand and forearm somatosensory activations in primary somatosensory areas. These results indicated that the device is well suited for small-bodied animal somatosensory studies. en-copyright= kn-copyright= en-aut-name=WangChenyu en-aut-sei=Wang en-aut-mei=Chenyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ImaiHirohiko en-aut-sei=Imai en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukunagaMasaki en-aut-sei=Fukunaga en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoHiroki en-aut-sei=Yamamoto en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YuYinghua en-aut-sei=Yu en-aut-mei=Yinghua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SekiKazuhiko en-aut-sei=Seki en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HanakawaTakashi en-aut-sei=Hanakawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UmedaTatsuya en-aut-sei=Umeda en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YangJiajia en-aut-sei=Yang en-aut-mei=Jiajia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Innovation Research Center for Quantum Medicine, Gifu University School of Medicine kn-affil= affil-num=3 en-affil=Section of Brain Function Information, National Institute for Physiological Sciences kn-affil= affil-num=4 en-affil=Graduate School of Human and Environmental Studies, Kyoto University kn-affil= affil-num=5 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurophysiology, National Center of Neurology and Psychiatry kn-affil= affil-num=7 en-affil=Department of Integrated Neuroanatomy and Neuroimaging, Kyoto University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Integrated Neuroanatomy and Neuroimaging, Kyoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=primary somatosensory cortex kn-keyword=primary somatosensory cortex en-keyword=small-bodied animals kn-keyword=small-bodied animals en-keyword=tactile stimulation device kn-keyword=tactile stimulation device en-keyword=ultrahigh-field magnetic resonance imaging kn-keyword=ultrahigh-field magnetic resonance imaging END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=11 article-no= start-page=6155 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Top-Down Stereolithography-Based System for Additive Manufacturing of Zirconia for Dental Applications en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigated the feasibility and effectiveness of a commercial top-down stereolithography (SLA)-based system for the additive manufacturing of zirconia dental prostheses. Yttria-stabilized zirconia–resin slurries were prepared, and zirconia objects were fabricated using a top-down SLA system. Thermogravimetric–differential thermal analysis was used to examine the resin, while X-ray fluorescence spectroscopy and X-ray diffraction were used to analyze the printed samples. The microstructures of additively manufactured and subtractively manufactured zirconia were compared using field emission scanning electron microscopy (FE-SEM) before and after sintering. Biaxial flexural strength tests were also conducted to evaluate mechanical properties. The green bodies obtained via additive manufacturing exhibited uniform layering with strong interlayer adhesion. After sintering, the structures were dense with minimal porosity. However, compared to subtractively manufactured zirconia, the additively manufactured specimens showed slightly higher porosity and lower biaxial flexural strength. The results demonstrate the potential of SLA-based additive manufacturing for dental zirconia applications while also highlighting its current mechanical limitations. The study also showed that using a blade to evenly spread viscous slurry layers in a top-down SLA system can effectively reduce oxygen inhibition at the surface and relieve internal stresses during the layer-by-layer printing process, offering a promising direction for clinical adaptation. en-copyright= kn-copyright= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SpirrettFiona en-aut-sei=Spirrett en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaruoYukinori en-aut-sei=Maruo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaYasuhiro en-aut-sei=Yoshida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Van MeerbeekBart en-aut-sei=Van Meerbeek en-aut-mei=Bart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KiriharaSoshu en-aut-sei=Kirihara en-aut-mei=Soshu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=National Institute of Advanced Industrial Science and Technology (AIST), Health and Medical Research Institute kn-affil= affil-num=2 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School kn-affil= affil-num=3 en-affil=Joining and Welding Research Institute, Osaka University kn-affil= affil-num=4 en-affil=Department of Prosthodontics, Okayama University kn-affil= affil-num=5 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=6 en-affil=BIOMAT, Department of Oral Health Sciences, KU Leuven kn-affil= affil-num=7 en-affil=Joining and Welding Research Institute, Osaka University kn-affil= en-keyword=additive manufacturing kn-keyword=additive manufacturing en-keyword=subtractive manufacturing kn-keyword=subtractive manufacturing en-keyword=dental prosthesis kn-keyword=dental prosthesis en-keyword=ceramic prosthesis kn-keyword=ceramic prosthesis en-keyword=zirconia laminates kn-keyword=zirconia laminates en-keyword=stereolithography kn-keyword=stereolithography en-keyword=thermogravimetry–differential thermal analysis kn-keyword=thermogravimetry–differential thermal analysis en-keyword=X-ray diffraction kn-keyword=X-ray diffraction en-keyword=scanning electron microscopy kn-keyword=scanning electron microscopy END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=40 article-no= start-page=3355- end-page=3364 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Plain language summary: tarlatamab for patients with previously treated small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=AhnMyung-Ju en-aut-sei=Ahn en-aut-mei=Myung-Ju kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChoByoung Chul en-aut-sei=Cho en-aut-mei=Byoung Chul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FelipEnriqueta en-aut-sei=Felip en-aut-mei=Enriqueta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KorantzisIppokratis en-aut-sei=Korantzis en-aut-mei=Ippokratis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MajemMargarita en-aut-sei=Majem en-aut-mei=Margarita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Juan-VidalOscar en-aut-sei=Juan-Vidal en-aut-mei=Oscar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HandzhievSabin en-aut-sei=Handzhiev en-aut-mei=Sabin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IzumiHiroki en-aut-sei=Izumi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LeeJong-Seok en-aut-sei=Lee en-aut-mei=Jong-Seok kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DziadziuszkoRafal en-aut-sei=Dziadziuszko en-aut-mei=Rafal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WolfJürgen en-aut-sei=Wolf en-aut-mei=Jürgen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=BlackhallFiona en-aut-sei=Blackhall en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ReckMartin en-aut-sei=Reck en-aut-mei=Martin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AlvarezJean Bustamante en-aut-sei=Alvarez en-aut-mei=Jean Bustamante kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HummelHorst-Dieter en-aut-sei=Hummel en-aut-mei=Horst-Dieter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=DingemansAnne-Marie C. en-aut-sei=Dingemans en-aut-mei=Anne-Marie C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SandsJacob en-aut-sei=Sands en-aut-mei=Jacob kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=AkamatsuHiroaki en-aut-sei=Akamatsu en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OwonikokoTaofeek K. en-aut-sei=Owonikoko en-aut-mei=Taofeek K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=RamalingamSuresh S. en-aut-sei=Ramalingam en-aut-mei=Suresh S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=BorghaeiHossein en-aut-sei=Borghaei en-aut-mei=Hossein kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=JohnsonMelissa L. en-aut-sei=Johnson en-aut-mei=Melissa L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HuangShuang en-aut-sei=Huang en-aut-mei=Shuang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=MukherjeeSujoy en-aut-sei=Mukherjee en-aut-mei=Sujoy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=MinochaMukul en-aut-sei=Minocha en-aut-mei=Mukul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=JiangTony en-aut-sei=Jiang en-aut-mei=Tony kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MartinezPablo en-aut-sei=Martinez en-aut-mei=Pablo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=AndersonErik S. en-aut-sei=Anderson en-aut-mei=Erik S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=Paz-AresLuis en-aut-sei=Paz-Ares en-aut-mei=Luis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Samsung Medical Center, Sungkyunkwan University School of Medicine kn-affil= affil-num=2 en-affil=Yonsei Cancer Center, Yonsei University College of Medicine kn-affil= affil-num=3 en-affil=Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology kn-affil= affil-num=4 en-affil=Department of Medical Oncology, Saint Loukas Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Hospital de la Santa Creu i Sant Pau kn-affil= affil-num=7 en-affil= kn-affil= affil-num=8 en-affil=Klinische Abteilung für Pneumologie, Universitätsklinikum Krems kn-affil= affil-num=9 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital East kn-affil= affil-num=10 en-affil=Seoul National University Bundang Hospital kn-affil= affil-num=11 en-affil=Department of Oncology and Radiotherapy and Early Phase Clinical Trials Center, Medical University of Gdansk kn-affil= affil-num=12 en-affil=Department of Internal Medicine, Center for Integrated Oncology, University Hospital Cologne kn-affil= affil-num=13 en-affil=Christie NHS Foundation Trust and University of Manchester kn-affil= affil-num=14 en-affil=Lungen Clinic, Airway Research Center North, German Center for Lung Research kn-affil= affil-num=15 en-affil=West Virginia University Health Sciences Center kn-affil= affil-num=16 en-affil=Translational Oncology–Early Clinical Trial Unit, Comprehensive Cancer Center Mainfranken and Bavarian Cancer Research Center, Universitätsklinikum Würzburg kn-affil= affil-num=17 en-affil=Department of Pulmonary Medicine, Erasmus MC Cancer Institute kn-affil= affil-num=18 en-affil=Dana–Farber Cancer Institute, Harvard Medical School kn-affil= affil-num=19 en-affil=Wakayama Medical University Hospital kn-affil= affil-num=20 en-affil=Division of Hematology–Oncology, Hillman Cancer Center, University of Pittsburgh Medical Center kn-affil= affil-num=21 en-affil=Winship Cancer Institute of Emory University kn-affil= affil-num=22 en-affil=Fox Chase Cancer Center kn-affil= affil-num=23 en-affil=Sarah Cannon Research Institute at Tennessee Oncology kn-affil= affil-num=24 en-affil=Amgen kn-affil= affil-num=25 en-affil=Amgen kn-affil= affil-num=26 en-affil=Amgen kn-affil= affil-num=27 en-affil=Amgen kn-affil= affil-num=28 en-affil=Amgen kn-affil= affil-num=29 en-affil=Amgen kn-affil= affil-num=30 en-affil=Hospital Universitario 12 de Octubre, CNIO-H12o Lung Cancer Unit, Complutense University and Ciberonc kn-affil= en-keyword=Clinical trials kn-keyword=Clinical trials en-keyword=DeLLphi-301 kn-keyword=DeLLphi-301 en-keyword=DLL3 kn-keyword=DLL3 en-keyword=Immunotherapy kn-keyword=Immunotherapy en-keyword=SCLC kn-keyword=SCLC en-keyword=Small cell lung cancer kn-keyword=Small cell lung cancer en-keyword=T cell kn-keyword=T cell en-keyword=Tarlatamab kn-keyword=Tarlatamab END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Employment of artificial intelligence for an unbiased evaluation regarding the recovery of right ventricular function after mitral valve transcatheter edge-to-edge repair en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims Long-standing severe mitral regurgitation (MR) leads to left atrial (LA) enlargement, elevated pulmonary artery pressures, and ultimately right heart failure. While mitral valve transcatheter edge-to-edge repair (M-TEER) alleviates left-sided volume overload, its impact on right ventricular (RV) recovery is unclear. This study aims to use both conventional echocardiography and artificial intelligence to assess the recovery of RV function in patients undergoing M-TEER for severe MR.
Methods and results The change in RV function from baseline to 3-month follow-up was analysed in a dual-centre registry of patients undergoing M-TEER for severe MR. RV function was conventionally assessed by measuring the tricuspid annular plane systolic excursion (TAPSE). Additionally, RV function was evaluated using a deep learning model that predicts RV ejection fraction (RVEF) based on two-dimensional apical four-chamber view echocardiographic videos. Among the 851 patients who underwent M-TEER, the 1-year survival rate was 86.8%. M-TEER resulted in a significant reduction in both LA volume and estimated systolic pulmonary artery pressure (sPAP) levels (median LA volume: from 123 ml [interquartile range, IQR 92–169 ml] to 104 ml [IQR 78–142 ml], p < 0.001; median sPAP: from 46 mmHg [IQR 35–58 mmHg] to 41 mmHg [IQR 32–54 mmHg], p = 0.036). In contrast, TAPSE remained unchanged (median: from 17 mm [IQR 14–21 mm] to 18 mm [IQR 15–21 mm], p = 0.603). The deep learning model confirmed this finding, showing no significant change in predicted RVEF after M-TEER (median: from 43.1% [IQR 39.1–47.4%] to 43.2% [IQR 39.2–47.2%], p = 0.475).
Conclusions While M-TEER improves left-sided haemodynamics, it does not lead to significant RV function recovery, as confirmed by both conventional echocardiography and artificial intelligence. This finding underscores the importance of treating patients before irreversible right heart damage occurs. en-copyright= kn-copyright= en-aut-name=FortmeierVera en-aut-sei=Fortmeier en-aut-mei=Vera kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HesseAmelie en-aut-sei=Hesse en-aut-mei=Amelie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TrenkwalderTeresa en-aut-sei=Trenkwalder en-aut-mei=Teresa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TokodiMárton en-aut-sei=Tokodi en-aut-mei=Márton kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KovácsAttila en-aut-sei=Kovács en-aut-mei=Attila kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=RippenElena en-aut-sei=Rippen en-aut-mei=Elena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TervoorenJule en-aut-sei=Tervooren en-aut-mei=Jule kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FettMichelle en-aut-sei=Fett en-aut-mei=Michelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HarmsenGerhard en-aut-sei=Harmsen en-aut-mei=Gerhard kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KühleinMoritz en-aut-sei=Kühlein en-aut-mei=Moritz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=CovarrubiasHéctor Alfonso Alvarez en-aut-sei=Covarrubias en-aut-mei=Héctor Alfonso Alvarez kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=von ScheidtMoritz en-aut-sei=von Scheidt en-aut-mei=Moritz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=RoskiFerdinand en-aut-sei=Roski en-aut-mei=Ferdinand kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=GerçekMuhammed en-aut-sei=Gerçek en-aut-mei=Muhammed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SchusterTibor en-aut-sei=Schuster en-aut-mei=Tibor kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MayrN. Patrick en-aut-sei=Mayr en-aut-mei=N. Patrick kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=XhepaErion en-aut-sei=Xhepa en-aut-mei=Erion kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=LaugwitzKarl‐Ludwig en-aut-sei=Laugwitz en-aut-mei=Karl‐Ludwig kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=JonerMichael en-aut-sei=Joner en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=RudolphVolker en-aut-sei=Rudolph en-aut-mei=Volker kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=LachmannMark en-aut-sei=Lachmann en-aut-mei=Mark kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of General and Interventional Cardiology, Heart and Diabetes Center Northrhine-Westfalia, Ruhr University Bochum kn-affil= affil-num=2 en-affil=Department of Internal Medicine I, Klinikum rechts der Isar, TUM University Hospital, School of Medicine and Health, Technical University of Munich kn-affil= affil-num=3 en-affil=DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance kn-affil= affil-num=4 en-affil=Heart and Vascular Center, Semmelweis University kn-affil= affil-num=5 en-affil=Heart and Vascular Center, Semmelweis University kn-affil= affil-num=6 en-affil=Department of Internal Medicine I, Klinikum rechts der Isar, TUM University Hospital, School of Medicine and Health, Technical University of Munich kn-affil= affil-num=7 en-affil=Department of Internal Medicine I, Klinikum rechts der Isar, TUM University Hospital, School of Medicine and Health, Technical University of Munich kn-affil= affil-num=8 en-affil=Department of General and Interventional Cardiology, Heart and Diabetes Center Northrhine-Westfalia, Ruhr University Bochum kn-affil= affil-num=9 en-affil=Department of Physics, University of Johannesburg kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Okayama University kn-affil= affil-num=11 en-affil=Department of Cardiovascular Diseases, German Heart Center Munich, School of Medicine and Health, TUM University Hospital, Technical University of Munich kn-affil= affil-num=12 en-affil=Department of Cardiovascular Diseases, German Heart Center Munich, School of Medicine and Health, TUM University Hospital, Technical University of Munich kn-affil= affil-num=13 en-affil=DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance kn-affil= affil-num=14 en-affil=Department of Cardiovascular Diseases, German Heart Center Munich, School of Medicine and Health, TUM University Hospital, Technical University of Munich kn-affil= affil-num=15 en-affil=Department of General and Interventional Cardiology, Heart and Diabetes Center Northrhine-Westfalia, Ruhr University Bochum kn-affil= affil-num=16 en-affil=Department of Family Medicine, McGill University kn-affil= affil-num=17 en-affil=Institute of Anesthesiology, German Heart Center Munich, School of Medicine and Health, TUM University Hospital, Technical University of Munich kn-affil= affil-num=18 en-affil=DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance kn-affil= affil-num=19 en-affil=Department of Internal Medicine I, Klinikum rechts der Isar, TUM University Hospital, School of Medicine and Health, Technical University of Munich kn-affil= affil-num=20 en-affil=DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance kn-affil= affil-num=21 en-affil=Department of General and Interventional Cardiology, Heart and Diabetes Center Northrhine-Westfalia, Ruhr University Bochum kn-affil= affil-num=22 en-affil=Department of Internal Medicine I, Klinikum rechts der Isar, TUM University Hospital, School of Medicine and Health, Technical University of Munich kn-affil= en-keyword=Echocardiography kn-keyword=Echocardiography en-keyword=Mitral regurgitation kn-keyword=Mitral regurgitation en-keyword=Right ventricular dysfunction kn-keyword=Right ventricular dysfunction en-keyword=Deep learning kn-keyword=Deep learning en-keyword=Transcatheter edge-to-edge repair kn-keyword=Transcatheter edge-to-edge repair END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=2 article-no= start-page=euaf024 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SCN5A variant type-dependent risk prediction in Brugada syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims The variant in SCN5A with the loss of function (LOF) effect in the cardiac Na+ channel (Nav1.5) is the definitive cause for Brugada syndrome (BrS), and the functional analysis data revealed that LOF variants are associated with poor prognosis. However, which variant types (e.g. missense or non-missense) affect the prognoses of those variant carriers remain unelucidated.
Methods and results We defined SCN5A LOF variants as all non-missense and missense variants that produce peak INa < 65% of wild-type previously confirmed by patch-clamp studies. The study population consisted of 76 Japanese BrS patients (74% patients were male and the median age [IQR] at diagnosis was 28 [14–45] years) with LOF type of SCN5A variants: 40 with missense and 36 with non-missense variants. Non-missense variant carriers presented significantly more severe cardiac conduction disorder compared to the missense variant carriers. During follow-up periods of 9.0 [5.0–14.0] years, compared to missense variants, non-missense variants were significant risk factors of lifetime lethal arrhythmia events (LAEs) (P = 0.023). When focusing only on the missense variants that produce no peak INa, these missense variant carriers exhibited the same clinical outcomes as those with non-missense (log-rank P = 0.325). After diagnosis, however, both variant types were comparable in risk of LAEs (P = 0.155).
Conclusion We identified, for the first time, that SCN5A non-missense variants were associated with higher probability of LAE than missense variants in BrS patients though it did not change significantly after diagnosis. en-copyright= kn-copyright= en-aut-name=AizawaTakanori en-aut-sei=Aizawa en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MakiyamaTakeru en-aut-sei=Makiyama en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuangHai en-aut-sei=Huang en-aut-mei=Hai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImamuraTomohiko en-aut-sei=Imamura en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukuyamaMegumi en-aut-sei=Fukuyama en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SonodaKeiko en-aut-sei=Sonoda en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatoKoichi en-aut-sei=Kato en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraYuko en-aut-sei=Nakamura en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HoshinoKenji en-aut-sei=Hoshino en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OzawaJunichi en-aut-sei=Ozawa en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SuzukiHiroshi en-aut-sei=Suzuki en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YasudaKazushi en-aut-sei=Yasuda en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AokiHisaaki en-aut-sei=Aoki en-aut-mei=Hisaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KuritaTakashi en-aut-sei=Kurita en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YoshidaYoko en-aut-sei=Yoshida en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SuzukiTsugutoshi en-aut-sei=Suzuki en-aut-mei=Tsugutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakamuraYoshihide en-aut-sei=Nakamura en-aut-mei=Yoshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OgawaYoshiharu en-aut-sei=Ogawa en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YamagamiShintaro en-aut-sei=Yamagami en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FukudaMasakazu en-aut-sei=Fukuda en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OnoMakoto en-aut-sei=Ono en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KondoHidekazu en-aut-sei=Kondo en-aut-mei=Hidekazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=TakahashiNaohiko en-aut-sei=Takahashi en-aut-mei=Naohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=OhnoSeiko en-aut-sei=Ohno en-aut-mei=Seiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NakagawaYoshihisa en-aut-sei=Nakagawa en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=OnoKoh en-aut-sei=Ono en-aut-mei=Koh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=HorieMinoru en-aut-sei=Horie en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine , 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 , kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= affil-num=6 en-affil=Medical Genome Center, National Cerebral and Cardiovascular Center kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= affil-num=8 en-affil=Department of Public Health, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Tsuchiura Kyodo General Hospital kn-affil= affil-num=10 en-affil=Department of Cardiology, Saitama Children’s Medical Center kn-affil= affil-num=11 en-affil=Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=12 en-affil=Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital kn-affil= affil-num=13 en-affil=Department of Pediatric Cardiology, Aichi Children’s Health and Medical Center kn-affil= affil-num=14 en-affil=Department of Pediatric Cardiology, Osaka Women’s and Children’s Hospital kn-affil= affil-num=15 en-affil=Division of Cardiovascular Center, Kindai University School of Medicine kn-affil= affil-num=16 en-affil=Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital kn-affil= affil-num=17 en-affil=Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital kn-affil= affil-num=18 en-affil=Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital kn-affil= affil-num=19 en-affil=Division of Cardiology, Hyogo Prefectural Kobe Children’s Hospital kn-affil= affil-num=20 en-affil=Department of Cardiology, Tenri Hospital kn-affil= affil-num=21 en-affil=Department of Cardiovascular Therapeutics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=22 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=24 en-affil=Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=25 en-affil=Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University kn-affil= affil-num=26 en-affil=Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University kn-affil= affil-num=27 en-affil=Medical Genome Center, National Cerebral and Cardiovascular Center kn-affil= affil-num=28 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= affil-num=29 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=30 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= en-keyword=Brugada syndrome kn-keyword=Brugada syndrome en-keyword=SCN5A kn-keyword=SCN5A en-keyword=Lethal arrhythmia event kn-keyword=Lethal arrhythmia event en-keyword=Variant type kn-keyword=Variant type en-keyword=Loss of function kn-keyword=Loss of function END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=7 article-no= start-page=002112 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) from the Animal dsRNA and ssRNA(−) Viruses Subcommittee, 2025 en-subtitle= kn-subtitle= en-abstract= kn-abstract=RNA viruses are ubiquitous in the environment and are important pathogens of humans, animals and plants. In 2024, the International Committee on Taxonomy of Viruses Animal dsRNA and ssRNA(−) Viruses Subcommittee submitted 18 taxonomic proposals for consideration. These proposals expanded the known virosphere by classifying 9 new genera and 88 species for newly detected virus genomes. Of note, newly established species expand the large family of Rhabdoviridae to 580 species. A new species in the family Arenaviridae includes a virus detected in Antarctic fish with a unique split nucleoprotein ORF. Additionally, four new species were established for historically isolated viruses with previously unsequenced genomes. Furthermore, three species were abolished due to incomplete genome sequence information, and one family was moved from being unassigned in the phylum Negarnaviricota into a subphylum and order. Herein, we summarize the 18 ratified taxonomic proposals and the general features of the current taxonomy, thereby supporting public and animal health responses. en-copyright= kn-copyright= en-aut-name=HughesHolly R. en-aut-sei=Hughes en-aut-mei=Holly R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BallingerMatthew J. en-aut-sei=Ballinger en-aut-mei=Matthew J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BaoYiming en-aut-sei=Bao en-aut-mei=Yiming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BejermanNicolas en-aut-sei=Bejerman en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BlasdellKim R. en-aut-sei=Blasdell en-aut-mei=Kim R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BrieseThomas en-aut-sei=Briese en-aut-mei=Thomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BrignoneJulia en-aut-sei=Brignone en-aut-mei=Julia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CarreraJean Paul en-aut-sei=Carrera en-aut-mei=Jean Paul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=De ConinckLander en-aut-sei=De Coninck en-aut-mei=Lander kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=de SouzaWilliam Marciel en-aut-sei=de Souza en-aut-mei=William Marciel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DebatHumberto en-aut-sei=Debat en-aut-mei=Humberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DietzgenRalf G. en-aut-sei=Dietzgen en-aut-mei=Ralf G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=DürrwaldRalf en-aut-sei=Dürrwald en-aut-mei=Ralf kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ErdinMert en-aut-sei=Erdin en-aut-mei=Mert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FooksAnthony R. en-aut-sei=Fooks en-aut-mei=Anthony R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ForbesKristian M. en-aut-sei=Forbes en-aut-mei=Kristian M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Freitas-AstúaJuliana en-aut-sei=Freitas-Astúa en-aut-mei=Juliana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=GarciaJorge B. en-aut-sei=Garcia en-aut-mei=Jorge B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=GeogheganJemma L. en-aut-sei=Geoghegan en-aut-mei=Jemma L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=GrimwoodRebecca M. en-aut-sei=Grimwood en-aut-mei=Rebecca M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HorieMasayuki en-aut-sei=Horie en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HyndmanTimothy H. en-aut-sei=Hyndman en-aut-mei=Timothy H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=JohneReimar en-aut-sei=Johne en-aut-mei=Reimar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KlenaJohn D. en-aut-sei=Klena en-aut-mei=John D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KooninEugene V. en-aut-sei=Koonin en-aut-mei=Eugene V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KostygovAlexei Y. en-aut-sei=Kostygov en-aut-mei=Alexei Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=KrupovicMart en-aut-sei=Krupovic en-aut-mei=Mart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KuhnJens H. en-aut-sei=Kuhn en-aut-mei=Jens H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=LetkoMichael en-aut-sei=Letko en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=LiJun-Min en-aut-sei=Li en-aut-mei=Jun-Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=LiuYiyun en-aut-sei=Liu en-aut-mei=Yiyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=MartinMaria Laura en-aut-sei=Martin en-aut-mei=Maria Laura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=MullNathaniel en-aut-sei=Mull en-aut-mei=Nathaniel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=NazarYael en-aut-sei=Nazar en-aut-mei=Yael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=NowotnyNorbert en-aut-sei=Nowotny en-aut-mei=Norbert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=NunesMárcio Roberto Teixeira en-aut-sei=Nunes en-aut-mei=Márcio Roberto Teixeira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=ØklandArnfinn Lodden en-aut-sei=Økland en-aut-mei=Arnfinn Lodden kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=RubbenstrothDennis en-aut-sei=Rubbenstroth en-aut-mei=Dennis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=RussellBrandy J. en-aut-sei=Russell en-aut-mei=Brandy J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=SchottEric en-aut-sei=Schott en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=SeifertStephanie en-aut-sei=Seifert en-aut-mei=Stephanie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=SenCarina en-aut-sei=Sen en-aut-mei=Carina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=ShedroffElizabeth en-aut-sei=Shedroff en-aut-mei=Elizabeth kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=SironenTarja en-aut-sei=Sironen en-aut-mei=Tarja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=SmuraTeemu en-aut-sei=Smura en-aut-mei=Teemu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=TavaresCamila Prestes Dos Santos en-aut-sei=Tavares en-aut-mei=Camila Prestes Dos Santos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=TeshRobert B. en-aut-sei=Tesh en-aut-mei=Robert B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=TilstonNatasha L. en-aut-sei=Tilston en-aut-mei=Natasha L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=TordoNoël en-aut-sei=Tordo en-aut-mei=Noël kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=VasilakisNikos en-aut-sei=Vasilakis en-aut-mei=Nikos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=WalkerPeter J. en-aut-sei=Walker en-aut-mei=Peter J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=WangFei en-aut-sei=Wang en-aut-mei=Fei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=WhitfieldAnna E. en-aut-sei=Whitfield en-aut-mei=Anna E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=WhitmerShannon L.M. en-aut-sei=Whitmer en-aut-mei=Shannon L.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= en-aut-name=WolfYuri I. en-aut-sei=Wolf en-aut-mei=Yuri I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=56 ORCID= en-aut-name=XiaHan en-aut-sei=Xia en-aut-mei=Han kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=57 ORCID= en-aut-name=YeGong-Yin en-aut-sei=Ye en-aut-mei=Gong-Yin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=58 ORCID= en-aut-name=YeZhuangxin en-aut-sei=Ye en-aut-mei=Zhuangxin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=59 ORCID= en-aut-name=YurchenkoVyacheslav en-aut-sei=Yurchenko en-aut-mei=Vyacheslav kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=60 ORCID= en-aut-name=ZhaoMingli en-aut-sei=Zhao en-aut-mei=Mingli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=61 ORCID= affil-num=1 en-affil=Centers for Disease Control and Prevention kn-affil= affil-num=2 en-affil=Biological Sciences, Mississippi State University kn-affil= affil-num=3 en-affil=National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and Instituto Nacional de Tecnología Agropecuaria (INTA) kn-affil= affil-num=5 en-affil=CSIRO Health and Biosecurity kn-affil= affil-num=6 en-affil=Center for Infection and Immunity, and Department of Epidemiology, Mailman School of Public Health, Columbia University kn-affil= affil-num=7 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=8 en-affil=Instituto Conmemorativo Gorgas de Estudios de la Salud kn-affil= affil-num=9 en-affil=Division of Clinical and Epidemiological Virology, KU Leuven kn-affil= affil-num=10 en-affil=Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky kn-affil= affil-num=11 en-affil=Instituto Nacional de Tecnología Agropecuaria (INTA) kn-affil= affil-num=12 en-affil=QAAFI, The University of Queensland kn-affil= affil-num=13 en-affil=Robert Koch Institut kn-affil= affil-num=14 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=15 en-affil=Animal and Plant Health Agency (APHA) kn-affil= affil-num=16 en-affil=Department of Biological Sciences, University of Arkansas kn-affil= affil-num=17 en-affil=Embrapa Cassava and Fruits kn-affil= affil-num=18 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=19 en-affil=Department of Microbiology and Immunology, University of Otago kn-affil= affil-num=20 en-affil=Department of Microbiology and Immunology, University of Otago kn-affil= affil-num=21 en-affil=Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University kn-affil= affil-num=22 en-affil=School of Veterinary Medicine, Murdoch University kn-affil= affil-num=23 en-affil=German Federal Institute for Risk Assessment kn-affil= affil-num=24 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=25 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=26 en-affil=Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health kn-affil= affil-num=27 en-affil=University of Ostrava kn-affil= affil-num=28 en-affil=Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit kn-affil= affil-num=29 en-affil=Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health kn-affil= affil-num=30 en-affil=Paul G. Allen School for Global Health, Washington State University kn-affil= affil-num=31 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=32 en-affil=National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences kn-affil= affil-num=33 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=34 en-affil=Department of Natural Sciences, Shawnee State University kn-affil= affil-num=35 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=36 en-affil=College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health kn-affil= affil-num=37 en-affil=Universidade Federal do Pará kn-affil= affil-num=38 en-affil=Pharmaq Analytiq kn-affil= affil-num=39 en-affil=Institute of Diagnostic Virology, Friedrich-Loeffler-Institut kn-affil= affil-num=40 en-affil=Centers for Disease Control and Prevention kn-affil= affil-num=41 en-affil=Institute of Marine and Environmental Technology, University of Maryland Center for Environmental Science kn-affil= affil-num=42 en-affil=Paul G. Allen School for Global Health, Washington State University kn-affil= affil-num=43 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=44 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=45 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=46 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=47 en-affil=Integrated Group of Aquaculture and Environmental Studies, Federal University of Paraná kn-affil= affil-num=48 en-affil=Department of Pathology, The University of Texas Medical Branch kn-affil= affil-num=49 en-affil=Department of Microbiology and Immunology, Indiana University School of Medicine kn-affil= affil-num=50 en-affil=Institut Pasteur kn-affil= affil-num=51 en-affil=Department of Pathology, The University of Texas Medical Branch kn-affil= affil-num=52 en-affil=University of Queensland kn-affil= affil-num=53 en-affil=Wuhan Institute of Virology, Chinese Academy of Sciences kn-affil= affil-num=54 en-affil=North Carolina State University kn-affil= affil-num=55 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=56 en-affil=Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health kn-affil= affil-num=57 en-affil=Wuhan Institute of Virology, Chinese Academy of Sciences kn-affil= affil-num=58 en-affil=Institute of Insect Sciences, Zhejiang University kn-affil= affil-num=59 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=60 en-affil=University of Ostrava kn-affil= affil-num=61 en-affil=Department of Pathobiology and Population Sciences, Royal Veterinary College kn-affil= END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=7 article-no= start-page=002114 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses from the Plant Viruses Subcommittee, 2025 en-subtitle= kn-subtitle= en-abstract= kn-abstract=In March 2025, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote, newly proposed taxa were added to those under the mandate of the Plant Viruses Subcommittee. In brief, 1 new order, 3 new families, 6 new genera, 2 new subgenera and 206 new species were created. Some taxa were reorganized. Genus Cytorhabdovirus in the family Rhabdoviridae was abolished and its taxa were redistributed into three new genera Alphacytorhabdovirus, Betacytorhabdovirus and Gammacytorhabdovirus. Genus Waikavirus in the family Secoviridae was reorganized into two subgenera (Actinidivirus and Ritunrivirus). One family and four previously unaffiliated genera were moved to the newly established order Tombendovirales. Twelve species not assigned to a genus were abolished. To comply with the ICTV mandate of a binomial format for virus species, eight species were renamed. Demarcation criteria in the absence of biological information were defined in the genus Ilarvirus (family Bromoviridae). This article presents the updated taxonomy put forth by the Plant Viruses Subcommittee and ratified by the ICTV. en-copyright= kn-copyright= en-aut-name=RubinoLuisa en-aut-sei=Rubino en-aut-mei=Luisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AbrahamianPeter en-aut-sei=Abrahamian en-aut-mei=Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AnWenxia en-aut-sei=An en-aut-mei=Wenxia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArandaMiguel A. en-aut-sei=Aranda en-aut-mei=Miguel A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Ascencio-IbañezJosé T. en-aut-sei=Ascencio-Ibañez en-aut-mei=José T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BejermanNicolas en-aut-sei=Bejerman en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BlouinArnaud G. en-aut-sei=Blouin en-aut-mei=Arnaud G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CandresseThierry en-aut-sei=Candresse en-aut-mei=Thierry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=CantoTomas en-aut-sei=Canto en-aut-mei=Tomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=CaoMengji en-aut-sei=Cao en-aut-mei=Mengji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=CarrJohn P. en-aut-sei=Carr en-aut-mei=John P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ChoWon Kyong en-aut-sei=Cho en-aut-mei=Won Kyong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ConstableFiona en-aut-sei=Constable en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=DasguptaIndranil en-aut-sei=Dasgupta en-aut-mei=Indranil kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=DebatHumberto en-aut-sei=Debat en-aut-mei=Humberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=DietzgenRalf G. en-aut-sei=Dietzgen en-aut-mei=Ralf G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=DigiaroMichele en-aut-sei=Digiaro en-aut-mei=Michele kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=DonaireLivia en-aut-sei=Donaire en-aut-mei=Livia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ElbeainoToufic en-aut-sei=Elbeaino en-aut-mei=Toufic kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FargetteDenis en-aut-sei=Fargette en-aut-mei=Denis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=FilardoFiona en-aut-sei=Filardo en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=FischerMatthias G. en-aut-sei=Fischer en-aut-mei=Matthias G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FontdevilaNuria en-aut-sei=Fontdevila en-aut-mei=Nuria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=FoxAdrian en-aut-sei=Fox en-aut-mei=Adrian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=Freitas-AstuaJuliana en-aut-sei=Freitas-Astua en-aut-mei=Juliana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=FuchsMarc en-aut-sei=Fuchs en-aut-mei=Marc kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=GeeringAndrew D.W. en-aut-sei=Geering en-aut-mei=Andrew D.W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=GhafariMahan en-aut-sei=Ghafari en-aut-mei=Mahan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=HafrénAnders en-aut-sei=Hafrén en-aut-mei=Anders kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=HammondJohn en-aut-sei=Hammond en-aut-mei=John kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=HammondRosemarie en-aut-sei=Hammond en-aut-mei=Rosemarie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=Hasiów-JaroszewskaBeata en-aut-sei=Hasiów-Jaroszewska en-aut-mei=Beata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=HebrardEugenie en-aut-sei=Hebrard en-aut-mei=Eugenie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=HernándezCarmen en-aut-sei=Hernández en-aut-mei=Carmen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=HilyJean-Michel en-aut-sei=Hily en-aut-mei=Jean-Michel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=HosseiniAhmed en-aut-sei=Hosseini en-aut-mei=Ahmed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=HullRoger en-aut-sei=Hull en-aut-mei=Roger kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=Inoue-NagataAlice K. en-aut-sei=Inoue-Nagata en-aut-mei=Alice K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=JordanRamon en-aut-sei=Jordan en-aut-mei=Ramon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=KreuzeJan F. en-aut-sei=Kreuze en-aut-mei=Jan F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=KrupovicMart en-aut-sei=Krupovic en-aut-mei=Mart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=KubotaKenji en-aut-sei=Kubota en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=KuhnJens H. en-aut-sei=Kuhn en-aut-mei=Jens H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=LeisnerScott en-aut-sei=Leisner en-aut-mei=Scott kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=LettJean-Michel en-aut-sei=Lett en-aut-mei=Jean-Michel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=LiChengyu en-aut-sei=Li en-aut-mei=Chengyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=LiFan en-aut-sei=Li en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=LiJun Min en-aut-sei=Li en-aut-mei=Jun Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=López-LambertiniPaola M. en-aut-sei=López-Lambertini en-aut-mei=Paola M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=Lopez-MoyaJuan J. en-aut-sei=Lopez-Moya en-aut-mei=Juan J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=MaclotFrancois en-aut-sei=Maclot en-aut-mei=Francois kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=MäkinenKristiina en-aut-sei=Mäkinen en-aut-mei=Kristiina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=MartinDarren en-aut-sei=Martin en-aut-mei=Darren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=MassartSebastien en-aut-sei=Massart en-aut-mei=Sebastien kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= en-aut-name=MillerW. Allen en-aut-sei=Miller en-aut-mei=W. Allen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=56 ORCID= en-aut-name=MohammadiMusa en-aut-sei=Mohammadi en-aut-mei=Musa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=57 ORCID= en-aut-name=MollovDimitre en-aut-sei=Mollov en-aut-mei=Dimitre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=58 ORCID= en-aut-name=MullerEmmanuelle en-aut-sei=Muller en-aut-mei=Emmanuelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=59 ORCID= en-aut-name=NagataTatsuya en-aut-sei=Nagata en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=60 ORCID= en-aut-name=Navas-CastilloJesús en-aut-sei=Navas-Castillo en-aut-mei=Jesús kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=61 ORCID= en-aut-name=NeriyaYutaro en-aut-sei=Neriya en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=62 ORCID= en-aut-name=Ochoa-CoronaFrancisco M. en-aut-sei=Ochoa-Corona en-aut-mei=Francisco M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=63 ORCID= en-aut-name=OhshimaKazusato en-aut-sei=Ohshima en-aut-mei=Kazusato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=64 ORCID= en-aut-name=PallásVicente en-aut-sei=Pallás en-aut-mei=Vicente kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=65 ORCID= en-aut-name=PappuHanu en-aut-sei=Pappu en-aut-mei=Hanu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=66 ORCID= en-aut-name=PetrzikKarel en-aut-sei=Petrzik en-aut-mei=Karel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=67 ORCID= en-aut-name=PoogginMikhail en-aut-sei=Pooggin en-aut-mei=Mikhail kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=68 ORCID= en-aut-name=PrigigalloMaria Isabella en-aut-sei=Prigigallo en-aut-mei=Maria Isabella kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=69 ORCID= en-aut-name=Ramos-GonzálezPedro L. en-aut-sei=Ramos-González en-aut-mei=Pedro L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=70 ORCID= en-aut-name=RibeiroSimone en-aut-sei=Ribeiro en-aut-mei=Simone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=71 ORCID= en-aut-name=Richert-PöggelerKatja R. en-aut-sei=Richert-Pöggeler en-aut-mei=Katja R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=72 ORCID= en-aut-name=RoumagnacPhilippe en-aut-sei=Roumagnac en-aut-mei=Philippe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=73 ORCID= en-aut-name=RoyAvijit en-aut-sei=Roy en-aut-mei=Avijit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=74 ORCID= en-aut-name=SabanadzovicSead en-aut-sei=Sabanadzovic en-aut-mei=Sead kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=75 ORCID= en-aut-name=ŠafářováDana en-aut-sei=Šafářová en-aut-mei=Dana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=76 ORCID= en-aut-name=SaldarelliPasquale en-aut-sei=Saldarelli en-aut-mei=Pasquale kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=77 ORCID= en-aut-name=SanfaçonHélène en-aut-sei=Sanfaçon en-aut-mei=Hélène kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=78 ORCID= en-aut-name=SarmientoCecilia en-aut-sei=Sarmiento en-aut-mei=Cecilia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=79 ORCID= en-aut-name=SasayaTakahide en-aut-sei=Sasaya en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=80 ORCID= en-aut-name=ScheetsKay en-aut-sei=Scheets en-aut-mei=Kay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=81 ORCID= en-aut-name=SchravesandeWillem E.W. en-aut-sei=Schravesande en-aut-mei=Willem E.W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=82 ORCID= en-aut-name=SealSusan en-aut-sei=Seal en-aut-mei=Susan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=83 ORCID= en-aut-name=ShimomotoYoshifumi en-aut-sei=Shimomoto en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=84 ORCID= en-aut-name=SõmeraMerike en-aut-sei=Sõmera en-aut-mei=Merike kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=85 ORCID= en-aut-name=StavoloneLivia en-aut-sei=Stavolone en-aut-mei=Livia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=86 ORCID= en-aut-name=StewartLucy R. en-aut-sei=Stewart en-aut-mei=Lucy R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=87 ORCID= en-aut-name=TeycheneyPierre-Yves en-aut-sei=Teycheney en-aut-mei=Pierre-Yves kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=88 ORCID= en-aut-name=ThomasJohn E. en-aut-sei=Thomas en-aut-mei=John E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=89 ORCID= en-aut-name=ThompsonJeremy R. en-aut-sei=Thompson en-aut-mei=Jeremy R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=90 ORCID= en-aut-name=TiberiniAntonio en-aut-sei=Tiberini en-aut-mei=Antonio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=91 ORCID= en-aut-name=TomitakaYasuhiro en-aut-sei=Tomitaka en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=92 ORCID= en-aut-name=TzanetakisIoannis en-aut-sei=Tzanetakis en-aut-mei=Ioannis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=93 ORCID= en-aut-name=UmberMarie en-aut-sei=Umber en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=94 ORCID= en-aut-name=UrbinoCica en-aut-sei=Urbino en-aut-mei=Cica kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=95 ORCID= en-aut-name=van den BurgHarrold A. en-aut-sei=van den Burg en-aut-mei=Harrold A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=96 ORCID= en-aut-name=Van der VlugtRené A.A. en-aut-sei=Van der Vlugt en-aut-mei=René A.A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=97 ORCID= en-aut-name=VarsaniArvind en-aut-sei=Varsani en-aut-mei=Arvind kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=98 ORCID= en-aut-name=VerhageAdriaan en-aut-sei=Verhage en-aut-mei=Adriaan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=99 ORCID= en-aut-name=VillamorDan en-aut-sei=Villamor en-aut-mei=Dan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=100 ORCID= en-aut-name=von BargenSusanne en-aut-sei=von Bargen en-aut-mei=Susanne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=101 ORCID= en-aut-name=WalkerPeter J. en-aut-sei=Walker en-aut-mei=Peter J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=102 ORCID= en-aut-name=WetzelThierry en-aut-sei=Wetzel en-aut-mei=Thierry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=103 ORCID= en-aut-name=WhitfieldAnna E. en-aut-sei=Whitfield en-aut-mei=Anna E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=104 ORCID= en-aut-name=WylieStephen J. en-aut-sei=Wylie en-aut-mei=Stephen J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=105 ORCID= en-aut-name=YangCaixia en-aut-sei=Yang en-aut-mei=Caixia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=106 ORCID= en-aut-name=ZerbiniF. Murilo en-aut-sei=Zerbini en-aut-mei=F. Murilo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=107 ORCID= en-aut-name=ZhangSong en-aut-sei=Zhang en-aut-mei=Song kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=108 ORCID= affil-num=1 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=2 en-affil=USDA-ARS, BARC, National Germplasm Resources Laboratory kn-affil= affil-num=3 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=4 en-affil=Centro de Edafología y Biología Aplicada del Segura-CSIC kn-affil= affil-num=5 en-affil=Department of Molecular and Structural Biochemistry, North Carolina State University kn-affil= affil-num=6 en-affil=Unidad de Fitopatología y Modelización Agrícola (UFYMA) INTA-CONICET kn-affil= affil-num=7 en-affil=Plant Protection Department kn-affil= affil-num=8 en-affil=UMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAE kn-affil= affil-num=9 en-affil=Margarita Salas Center for Biological Research (CIB-CSIC) Spanish Council for Scientific Research (CSIC) kn-affil= affil-num=10 en-affil=National Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest University kn-affil= affil-num=11 en-affil=Department of Plant Sciences, University of Cambridge kn-affil= affil-num=12 en-affil=Agriculture and Life Sciences Research Institute, Kangwon National University kn-affil= affil-num=13 en-affil=Agriculture Victoria Research, Department of Energy, Environment and Climate Action and School of Applied Systems Biology, La Trobe University kn-affil= affil-num=14 en-affil=University of Delhi South Campu kn-affil= affil-num=15 en-affil=Unidad de Fitopatología y Modelización Agrícola (UFYMA) INTA-CONICET kn-affil= affil-num=16 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=17 en-affil=CIHEAM, Istituto Agronomico Mediterraneo of Bari kn-affil= affil-num=18 en-affil=Centro de Edafología y Biología Aplicada del Segura-CSIC kn-affil= affil-num=19 en-affil=CIHEAM, Istituto Agronomico Mediterraneo of Bari kn-affil= affil-num=20 en-affil=Virus South Data kn-affil= affil-num=21 en-affil=Queensland Department of Primary Industries kn-affil= affil-num=22 en-affil=Max Planck Institute for Marine Microbiology kn-affil= affil-num=23 en-affil=Plant Protection Department kn-affil= affil-num=24 en-affil=Fera Science Ltd (Fera), York Biotech Campus kn-affil= affil-num=25 en-affil=Embrapa Cassava and Fruits, Brazilian Agricultural Research Corporation kn-affil= affil-num=26 en-affil=Plant Pathology, Cornell University kn-affil= affil-num=27 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=28 en-affil=Department of Biology, University of Oxford kn-affil= affil-num=29 en-affil=Swedish University of Agriculture kn-affil= affil-num=30 en-affil=USDA-ARS, USNA, Floral and Nursery Plants Research Unit kn-affil= affil-num=31 en-affil=USDA-ARS, BARC, Molecular Plant Pathology Laboratory kn-affil= affil-num=32 en-affil=Institute of Plant Protection-NRI kn-affil= affil-num=33 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro kn-affil= affil-num=34 en-affil=Instituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de Valencia-CSIC kn-affil= affil-num=35 en-affil=Institut Français de la Vigne et du Vin kn-affil= affil-num=36 en-affil=Vali-e-Asr University of Rafsanjan, Department of Plant Protection kn-affil= affil-num=37 en-affil=Retired from John Innes Centre kn-affil= affil-num=38 en-affil=Embrapa Hortaliças kn-affil= affil-num=39 en-affil=USDA-ARS, USNA, Floral and Nursery Plants Research Unit kn-affil= affil-num=40 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=41 en-affil=International Potato Center (CIP) kn-affil= affil-num=42 en-affil=Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit kn-affil= affil-num=43 en-affil=Institute for Plant Protection, NARO kn-affil= affil-num=44 en-affil=Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health kn-affil= affil-num=45 en-affil=Department of Biological Sciences, University of Toledo kn-affil= affil-num=46 en-affil=CIRAD, UMR PVBMT kn-affil= affil-num=47 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=48 en-affil=State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University kn-affil= affil-num=49 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=50 en-affil=Instituto de Patología Vegetal (IPAVE), INTA, Unidad de Fitopatología y Modelización Agrícola (UFYMA) INTA-CONICET kn-affil= affil-num=51 en-affil=Centre for Research in Agricultural Genomics, CRAG (CSIC-IRTA-UAB-UB) kn-affil= affil-num=52 en-affil=UMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAE kn-affil= affil-num=53 en-affil=Department of Agricultural Sciences, University of Helsinki kn-affil= affil-num=54 en-affil=Institute of Infectious Disease and Molecular Medicine, University of Cape Town kn-affil= affil-num=55 en-affil=Plant Pathology Laboratory, TERRA Gembloux Agro-Bio Tech, University of Liege kn-affil= affil-num=56 en-affil=Department of Plant Pathology, Entomology and Microbiology, Iowa State University kn-affil= affil-num=57 en-affil=Department of Plant Protection, Gorgan University of Agricultural Sciences and Natural Resources kn-affil= affil-num=58 en-affil=USDA-APHIS, Plant Protection and Quarantine kn-affil= affil-num=59 en-affil=CIRAD, AGAP Institut; AGAP Institut, University of Montpellier; CIRAD, INRAE kn-affil= affil-num=60 en-affil=Instituto de Ciências Biológicas, Universidade de Brasília kn-affil= affil-num=61 en-affil=Instituto de Hortofruticultura Subtropical y Mediterránea “La Mayora” (IHSM-UMA-CSIC), Consejo Superior de Investigaciones Científicas kn-affil= affil-num=62 en-affil=Utsunomiya University kn-affil= affil-num=63 en-affil=Oklahoma State University, Institute for Biosecurity & Microbial Forensics kn-affil= affil-num=64 en-affil=Saga University kn-affil= affil-num=65 en-affil=Instituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de Valencia-CSIC kn-affil= affil-num=66 en-affil=Department of Plant Pathology, Washington State University kn-affil= affil-num=67 en-affil=Institute of Plant Molecular Biology kn-affil= affil-num=68 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD kn-affil= affil-num=69 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=70 en-affil=Applied Molecular Biology Laboratory, Instituto Biológico de São Paulo kn-affil= affil-num=71 en-affil=Embrapa Recursos Genéticos e Biotecnologia kn-affil= affil-num=72 en-affil=Julius Kühn Institute, Federal Research Centre for Cultivated Plants, Institute for Epidemiology and Pathogen Diagnostics kn-affil= affil-num=73 en-affil=CIRAD, UMR PHIM kn-affil= affil-num=74 en-affil=USDA-ARS, BARC, Molecular Plant Pathology Laboratory, Beltsville, MD, USA kn-affil= affil-num=75 en-affil=Department of Agricultural Science and Plant Protection, Mississippi State University kn-affil= affil-num=76 en-affil=Department of Cell Biology and Genetics, Faculty of Science, Palacký University Olomouc kn-affil= affil-num=77 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=78 en-affil=Summerland Research and Development Centre, Agriculture and Agri-Food Canada kn-affil= affil-num=79 en-affil=Department of Chemistry and Biotechnology, Tallinn University of Technology kn-affil= affil-num=80 en-affil=Strategic Planning Headquarters, NARO kn-affil= affil-num=81 en-affil=Department of Plant Pathology, Ecology and Evolution, Oklahoma State University kn-affil= affil-num=82 en-affil=Molecular Plant Pathology, University of Amsterdam kn-affil= affil-num=83 en-affil=Natural Resources Institute, University of Greenwich kn-affil= affil-num=84 en-affil=Kochi Agricultural Research Center kn-affil= affil-num=85 en-affil=Department of Chemistry and Biotechnology, Tallinn University of Technology kn-affil= affil-num=86 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=87 en-affil=Currently unaffiliated kn-affil= affil-num=88 en-affil=CIRAD, UMR PVBMT & UMR PVBMT, Université de la Réunion kn-affil= affil-num=89 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=90 en-affil=Plant Health and Environment Laboratory kn-affil= affil-num=91 en-affil=Council for Agricultural Research and Economics, Research Centre for Plant Protection and Certification kn-affil= affil-num=92 en-affil=Institute for Plant Protection, NARO kn-affil= affil-num=93 en-affil=Department of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas System kn-affil= affil-num=94 en-affil=INRAE, UR ASTRO kn-affil= affil-num=95 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro kn-affil= affil-num=96 en-affil=Molecular Plant Pathology, University of Amsterdam kn-affil= affil-num=97 en-affil=Wageningen University and Research kn-affil= affil-num=98 en-affil=The Biodesign Center for Fundamental and Applied Microbiomics, Center for Evolution and Medicine, School of Life Sciences, Arizona State University kn-affil= affil-num=99 en-affil=Rijk Zwaan Breeding B.V. kn-affil= affil-num=100 en-affil=Department of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas System kn-affil= affil-num=101 en-affil=Humboldt-Universität zu Berlin, Thaer-Institute of Agricultural and Horticultural Sciences kn-affil= affil-num=102 en-affil=The University of Queensland kn-affil= affil-num=103 en-affil=Dienstleistungszentrum Ländlicher Raum Rheinpfalz kn-affil= affil-num=104 en-affil=North Carolina State University kn-affil= affil-num=105 en-affil=Food Futures Institute, Murdoch University kn-affil= affil-num=106 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=107 en-affil=Dep. de Fitopatologia/BIOAGRO, Universidade Federal de Viçosa kn-affil= affil-num=108 en-affil=National Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=6 article-no= start-page=466 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250617 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Artificial Intelligence Approach in Machine Learning-Based Modeling and Networking of the Coronavirus Pathogenesis Pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=The coronavirus pathogenesis pathway, which consists of severe acute respiratory syndrome (SARS) coronavirus infection and signaling pathways, including the interferon pathway, the transforming growth factor beta pathway, the mitogen-activated protein kinase pathway, the apoptosis pathway, and the inflammation pathway, is activated upon coronaviral infection. An artificial intelligence approach based on machine learning was utilized to develop models with images of the coronavirus pathogenesis pathway to predict the activation states. Data on coronaviral infection held in a database were analyzed with Ingenuity Pathway Analysis (IPA), a network pathway analysis tool. Data related to SARS coronavirus 2 (SARS-CoV-2) were extracted from more than 100,000 analyses and datasets in the IPA database. A total of 27 analyses, including nine analyses of SARS-CoV-2-infected human-induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes and fibroblasts, and a total of 22 analyses of SARS-CoV-2-infected lung adenocarcinoma (LUAD), were identified as being related to “human” and “SARS coronavirus 2” in the database. The coronavirus pathogenesis pathway was activated in SARS-CoV-2-infected iPSC-derived cells and LUAD cells. A prediction model was developed in Python 3.11 using images of the coronavirus pathogenesis pathway under different conditions. The prediction model of activation states of the coronavirus pathogenesis pathway may aid in treatment identification. en-copyright= kn-copyright= en-aut-name=TanabeShihori en-aut-sei=Tanabe en-aut-mei=Shihori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=QuaderSabina en-aut-sei=Quader en-aut-mei=Sabina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnoRyuichi en-aut-sei=Ono en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaHiroyoshi Y. en-aut-sei=Tanaka en-aut-mei=Hiroyoshi Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoAkihisa en-aut-sei=Yamamoto en-aut-mei=Akihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KojimaMotohiro en-aut-sei=Kojima en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PerkinsEdward J. en-aut-sei=Perkins en-aut-mei=Edward J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CabralHoracio en-aut-sei=Cabral en-aut-mei=Horacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=2 en-affil=Innovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion kn-affil= affil-num=3 en-affil=Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=4 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Mechanical Systems Engineering, Graduate School of Systems Design Tokyo Metropolitan University kn-affil= affil-num=6 en-affil=Department of Surgical Pathology, Kyoto Prefecture University of Medicine kn-affil= affil-num=7 en-affil=US Army Engineer Research and Development Center kn-affil= affil-num=8 en-affil=Department of Bioengineering, Graduate School of Engineering, The University of Tokyo kn-affil= en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=coronavirus kn-keyword=coronavirus en-keyword=coronaviral infection kn-keyword=coronaviral infection en-keyword=machine learning kn-keyword=machine learning en-keyword=pathway analysis kn-keyword=pathway analysis en-keyword=predictionmodel kn-keyword=predictionmodel en-keyword=molecular network kn-keyword=molecular network en-keyword=molecular pathway image kn-keyword=molecular pathway image en-keyword=network analysis kn-keyword=network analysis END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=7 article-no= start-page=001430 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250707 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genomic features of three major diarrhoeagenic Escherichia coli pathotypes in India en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background. Diarrhoea remains a major threat to children in developing nations, with diarrhoeagenic Escherichia coli (DEC) being the primary causative agent. Characterizing prevalent DEC strains is crucial, yet comprehensive genomic analyses of major DEC strains, including enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC) and enterotoxigenic E. coli (ETEC), are lacking in India.
Methods. We sequenced 24 EAEC and 23 EPEC strains from Indian patients with diarrhoea and conducted an extensive database search for DEC human isolates from India. Detailed phylogenetic analyses, virulence gene subtyping and examinations of accessory virulence and antimicrobial resistance (AMR) genes were performed.
Results. The analysed DEC strains included 32 EAEC, 25 EPEC, 32 ETEC and 1 each of the EPEC/ETEC-hybrid and ETEC/EAEC-hybrid pathotypes. These strains were predominantly classified into phylogroups A (35.2%) and B1 (41.8%) and dispersed within these phylogroups without pathotype-specific clustering. One ETEC strain was classified into cryptic clade 1. Subtypes of hallmark virulence genes varied substantially amongst strains in each pathotype, and 31 accessory virulence genes were detected either specifically within certain pathotypes or across multiple pathotypes at varying frequencies, indicating diversification of the virulence gene repertoire within each pathotype. Acquired AMR genes were found in 73.6% of the strains, with frequent identification of AMR genes for aminoglycosides (40.0%), β-lactams (64.8%), sulphonamides (49.5%) and trimethoprim (42.9%). Known quinolone-resistant mutations were found in 74.7% of the strains, whereas AMR genes for macrolide (30.8%), phenicol (11.0%) and tetracycline (27.4%) were less frequent.
Conclusions. The diverse virulence potential and trends in AMR gene prevalence amongst major DEC strains in India are highlighted in this study. Continuous monitoring of DEC strain characteristics is essential for the effective control and treatment of DEC infections in India. en-copyright= kn-copyright= en-aut-name=HoshikoYuki en-aut-sei=Hoshiko en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChowdhuryGoutam en-aut-sei=Chowdhury en-aut-mei=Goutam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitaharaKei en-aut-sei=Kitahara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GhoshDebjani en-aut-sei=Ghosh en-aut-mei=Debjani kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaganoDebora Satie en-aut-sei=Nagano en-aut-mei=Debora Satie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhnoAyumu en-aut-sei=Ohno en-aut-mei=Ayumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkunoMiki en-aut-sei=Okuno en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoTakeshi en-aut-sei=Yamamoto en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=DuttaShanta en-aut-sei=Dutta en-aut-mei=Shanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MukhopadhyayAsish K. en-aut-sei=Mukhopadhyay en-aut-mei=Asish K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OguraYoshitoshi en-aut-sei=Ogura en-aut-mei=Yoshitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=​Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine kn-affil= affil-num=2 en-affil=Collaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=3 en-affil=Collaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=4 en-affil=Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=5 en-affil=​Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine kn-affil= affil-num=6 en-affil=Collaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=7 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=​Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine kn-affil= affil-num=9 en-affil=​Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine kn-affil= affil-num=10 en-affil=​Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=11 en-affil=​Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=12 en-affil=​Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine kn-affil= en-keyword=antimicrobial resistance kn-keyword=antimicrobial resistance en-keyword=diarrhoeagenic Escherichia coli kn-keyword=diarrhoeagenic Escherichia coli en-keyword=genome kn-keyword=genome en-keyword=India kn-keyword=India en-keyword=virulence gene kn-keyword=virulence gene END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=7 article-no= start-page=902 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250711 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of an Antimicrobial Coating Film for Denture Lining Materials en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Denture hygiene is essential for the prevention of oral candidiasis, a condition frequently associated with Candida albicans colonization on denture surfaces. Cetylpyridinium chloride (CPC)-loaded montmorillonite (CPC-Mont) has demonstrated antimicrobial efficacy in tissue conditioners and demonstrates potential for use in antimicrobial coatings. In this study, we aimed to develop and characterize CPC-Mont-containing coating films for dentures, focusing on their physicochemical behaviors and antifungal efficacies. Methods: CPC was intercalated into sodium-type montmorillonite to prepare CPC-Mont; thereafter, films containing CPC-Mont were fabricated using emulsions of different polymer types (nonionic, cationic, and anionic). CPC loading, release, and recharging behaviors were assessed at various temperatures, and activation energies were calculated using Arrhenius plots. Antimicrobial efficacy against Candida albicans was evaluated for each film using standard microbial assays. Results: X-ray diffraction analysis confirmed the expansion of montmorillonite interlayer spacing by approximately 3 nm upon CPC loading. CPC-Mont showed temperature-dependent release and recharging behavior, with higher temperatures enhancing its performance. The activation energy for CPC release was 38 kJ/mol, while that for recharging was 26 kJ/mol. Nonionic emulsions supported uniform CPC-Mont dispersion and successful film formation, while cationic and anionic emulsions did not. CPC-Mont-containing coatings maintained antimicrobial activity against Candida albicans on dentures. Conclusions: CPC-Mont can be effectively incorporated into nonionic emulsion-based films to create antimicrobial coatings for denture applications. The films exhibited temperature-responsive, reversible CPC release and recharging behaviors, while maintaining antifungal efficacy, findings which suggest the potential utility of CPC-Mont-containing films as a practical strategy to prevent denture-related candidiasis. en-copyright= kn-copyright= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KameyamaTakeru en-aut-sei=Kameyama en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaruoYukinori en-aut-sei=Maruo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaYasuhiro en-aut-sei=Yoshida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Van MeerbeekBart en-aut-sei=Van Meerbeek en-aut-mei=Bart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkiharaTakumi en-aut-sei=Okihara en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=National Institute of Advanced Industrial Science and Technology (AIST), Health and Medical Research Institute kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Dental School, Advanced Research Center for Oral and Craniofacial Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Prosthodontics, Okayama University kn-affil= affil-num=5 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=6 en-affil=BIOMAT, Department of Oral Health Sciences, KU Leuvem kn-affil= affil-num=7 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=antimicrobial kn-keyword=antimicrobial en-keyword=denture liner kn-keyword=denture liner en-keyword=cetylpyridiniumchloride kn-keyword=cetylpyridiniumchloride en-keyword=drug release kn-keyword=drug release en-keyword=drug recharge kn-keyword=drug recharge END start-ver=1.4 cd-journal=joma no-vol=637 cd-vols= no-issue=8046 article-no= start-page=744 end-page=748 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Centrophilic retrotransposon integration via CENH3 chromatin in Arabidopsis en-subtitle= kn-subtitle= en-abstract= kn-abstract=In organisms ranging from vertebrates to plants, major components of centromeres are rapidly evolving repeat sequences, such as tandem repeats (TRs) and transposable elements (TEs), which harbour centromere-specific histone H3 (CENH3)1,2. Complete centromere structures recently determined in human and Arabidopsis suggest frequent integration and purging of retrotransposons within the TR regions of centromeres3,4,5. Despite the high impact of ‘centrophilic’ retrotransposons on the paradox of rapid centromere evolution, the mechanisms involved in centromere targeting remain poorly understood in any organism. Here we show that both Ty3 and Ty1 long terminal repeat retrotransposons rapidly turnover within the centromeric TRs of Arabidopsis species. We demonstrate that the Ty1/Copia element Tal1 (Transposon of Arabidopsis lyrata 1) integrates de novo into regions occupied by CENH3 in Arabidopsis thaliana, and that ectopic expansion of the CENH3 region results in spread of Tal1 integration regions. The integration spectra of chimeric TEs reveal the key structural variations responsible for contrasting chromatin-targeting specificities to centromeres versus gene-rich regions, which have recurrently converted during the evolution of these TEs. Our findings show the impact of centromeric chromatin on TE-mediated rapid centromere evolution, with relevance across eukaryotic genomes. en-copyright= kn-copyright= en-aut-name=TsukaharaSayuri en-aut-sei=Tsukahara en-aut-mei=Sayuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BousiosAlexandros en-aut-sei=Bousios en-aut-mei=Alexandros kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Perez-RomanEstela en-aut-sei=Perez-Roman en-aut-mei=Estela kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamaguchiSota en-aut-sei=Yamaguchi en-aut-mei=Sota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LeduqueBasile en-aut-sei=Leduque en-aut-mei=Basile kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoAimi en-aut-sei=Nakano en-aut-mei=Aimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaishMatthew en-aut-sei=Naish en-aut-mei=Matthew kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OsakabeAkihisa en-aut-sei=Osakabe en-aut-mei=Akihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ToyodaAtsushi en-aut-sei=Toyoda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoHidetaka en-aut-sei=Ito en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EderaAlejandro en-aut-sei=Edera en-aut-mei=Alejandro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TominagaSayaka en-aut-sei=Tominaga en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Juliarni en-aut-sei=Juliarni en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatoKae en-aut-sei=Kato en-aut-mei=Kae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OdaShoko en-aut-sei=Oda en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=InagakiSoichi en-aut-sei=Inagaki en-aut-mei=Soichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=LorkovićZdravko en-aut-sei=Lorković en-aut-mei=Zdravko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NagakiKiyotaka en-aut-sei=Nagaki en-aut-mei=Kiyotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=BergerFrédéric en-aut-sei=Berger en-aut-mei=Frédéric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KawabeAkira en-aut-sei=Kawabe en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=QuadranaLeandro en-aut-sei=Quadrana en-aut-mei=Leandro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HendersonIan en-aut-sei=Henderson en-aut-mei=Ian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KakutaniTetsuji en-aut-sei=Kakutani en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=2 en-affil=School of Life Sciences, University of Sussex kn-affil= affil-num=3 en-affil=School of Life Sciences, University of Sussex kn-affil= affil-num=4 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=5 en-affil=Institute of Plant Sciences Paris‐Saclay (IPS2), Centre National de la Recherche Scientifique, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement, Université Evry, Université Paris kn-affil= affil-num=6 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Plant Sciences, University of Cambridge kn-affil= affil-num=8 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=9 en-affil=Center for Genetic Resource Information, National Institute of Genetics kn-affil= affil-num=10 en-affil=Faculty of Science, Hokkaido University kn-affil= affil-num=11 en-affil=Institute of Plant Sciences Paris‐Saclay (IPS2), Centre National de la Recherche Scientifique, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement, Université Evry, Université Paris kn-affil= affil-num=12 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=13 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=14 en-affil=Department of Integrated Genetics, National Institute of Genetics kn-affil= affil-num=15 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=16 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=17 en-affil=Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna BioCenter (VBC) kn-affil= affil-num=18 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=19 en-affil=Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna BioCenter (VBC) kn-affil= affil-num=20 en-affil=Faculty of Life Sciences, Kyoto Sangyo University kn-affil= affil-num=21 en-affil=Institute of Plant Sciences Paris‐Saclay (IPS2), Centre National de la Recherche Scientifique, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement, Université Evry, Université Paris kn-affil= affil-num=22 en-affil=Department of Plant Sciences, University of Cambridge kn-affil= affil-num=23 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=18 article-no= start-page=2413456 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250320 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cryo-EM Analysis of a Tri-Heme Cytochrome-Associated RC-LH1 Complex from the Marine Photoheterotrophic Bacterium Dinoroseobacter Shibae en-subtitle= kn-subtitle= en-abstract= kn-abstract=The reaction center-light harvesting 1 (RC-LH1) complex converts solar energy into electrical energy, driving the initiation of photosynthesis. The authors present a cryo-electron microscopy structure of the RC-LH1 isolated from a marine photoheterotrophic bacterium Dinoroseobacter shibae. The RC comprises four subunits, including a three-heme cytochrome (Cyt) c protein, and is surrounded by a closed LH ring composed of 17 pairs of antenna subunits. Notably, a novel subunit with an N-terminal “helix-turn-helix” motif embedded in the gap between the RC and the LH ring is identified. The purified RC-LH1 complex exhibits high stability in solutions containing Mg2+ or Ca2+. The periplasmic Cyt c2 is predicted to bind at the junction between the Cyt subunit and the membrane plane, enabling electron transfer from Cyt c2 to the proximal heme of the tri-heme Cyt, and subsequently to the special pair of bacteriochlorophylls. These findings provide structural insights into the efficient energy and electron transfer processes within a distinct type of RC-LH1, and shed light on evolutionary adaptations of photosynthesis. en-copyright= kn-copyright= en-aut-name=WangWeiwei en-aut-sei=Wang en-aut-mei=Weiwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiuYanting en-aut-sei=Liu en-aut-mei=Yanting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GuJiayi en-aut-sei=Gu en-aut-mei=Jiayi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AnShaoya en-aut-sei=An en-aut-mei=Shaoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaCheng en-aut-sei=Ma en-aut-mei=Cheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GaoHaichun en-aut-sei=Gao en-aut-mei=Haichun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=JiaoNianzhi en-aut-sei=Jiao en-aut-mei=Nianzhi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShenJian‐Ren en-aut-sei=Shen en-aut-mei=Jian‐Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BeattyJohn Thomas en-aut-sei=Beatty en-aut-mei=John Thomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KoblížekMichal en-aut-sei=Koblížek en-aut-mei=Michal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ZhangXing en-aut-sei=Zhang en-aut-mei=Xing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ZhengQiang en-aut-sei=Zheng en-aut-mei=Qiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ChenJing‐Hua en-aut-sei=Chen en-aut-mei=Jing‐Hua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=College of Life Sciences, Zhejiang University kn-affil= affil-num=2 en-affil=State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University kn-affil= affil-num=3 en-affil=College of Life Sciences, Zhejiang University kn-affil= affil-num=4 en-affil=Department of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of Medicine kn-affil= affil-num=5 en-affil=Department of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of Medicine kn-affil= affil-num=6 en-affil=College of Life Sciences, Zhejiang University kn-affil= affil-num=7 en-affil=State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University kn-affil= affil-num=8 en-affil=Research Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Department of Microbiology & Immunology, University of British Columbia kn-affil= affil-num=10 en-affil=Laboratory of Anoxygenic Phototrophs, Institute of Microbiology, Czech Academy of Science kn-affil= affil-num=11 en-affil=Department of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of Medicine kn-affil= affil-num=12 en-affil=State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University kn-affil= affil-num=13 en-affil=College of Life Sciences, Zhejiang University kn-affil= en-keyword=energy transfer kn-keyword=energy transfer en-keyword=photoheterotrophic bacteria kn-keyword=photoheterotrophic bacteria en-keyword=photosynthesis kn-keyword=photosynthesis en-keyword=reaction center kn-keyword=reaction center en-keyword=structure kn-keyword=structure END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=4 article-no= start-page=773 end-page=782 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Japanese translation of the Functional Assessment of Cancer Therapy-Breast + 4 (FACT-B + 4) following international guidelines: a verification of linguistic validity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background For breast cancer patients, postoperative lymphedema and upper limb movement disorders are serious complications that absolutely reduce their quality of life (QOL). To evaluate this serious complication, we used “Quick Dash” or “FACT-B”, which can assess a patient's physical, social, emotional, and functional health status. To evaluate their breast cancer surgery-related dysfunction correctly, “FACT-B + 4” was created by adding four questions about “arm swelling'' and “tenderness”. We have translated it into Japanese according to international translation guidelines.
Methods At the beginning, we contacted FACT headquarters that we would like to create a Japanese version of FACT-B + 4. They formed the FACIT Trans Team (FACIT) following international translation procedures, and then, we began translating according to them. The steps are 1: perform “Forward and Reverse translations” to create a “Preliminary Japanese version”, 2: request the cooperation of 5 breast cancer patients and “conduct a pilot study” and “questionnaire survey”, and 3: amendments and final approval based on pilot study results and clinical perspectives.
Result In Step1, FACIT requested faithful translation of the words, verbs, and nouns from the original text. In Step2, patients reported that they felt uncomfortable with the Japanese version words such as “numb'' and “stiffness'' and felt that it might be difficult to describe their symptoms accurately. In Step3, we readjusted the translation to be more concise and closer to common Japanese language, and performed “Step1” again to ensure that the translation definitely retained the meaning of the original.
Conclusion A Japanese version of FACT has existed until now, but there was no Japanese version of FACT-B + 4, which adds four additional items to evaluate swelling and pain in the upper limbs. This time, we have created a Japanese version that has been approved by FACT. en-copyright= kn-copyright= en-aut-name=TsukiokiTakahiro en-aut-sei=Tsukioki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakataNozomu en-aut-sei=Takata en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DennisSaya R. en-aut-sei=Dennis en-aut-mei=Saya R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TerataKaori en-aut-sei=Terata en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SagaraYasuaki en-aut-sei=Sagara en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakaiTakehiko en-aut-sei=Sakai en-aut-mei=Takehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakayamaShin en-aut-sei=Takayama en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KitagawaDai en-aut-sei=Kitagawa en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KikawaYuichiro en-aut-sei=Kikawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakahashiYuko en-aut-sei=Takahashi en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwataniTsuguo en-aut-sei=Iwatani en-aut-mei=Tsuguo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujisawaTomomi en-aut-sei=Fujisawa en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Simpson Querrey Biomedical Research Center, Northwestern University kn-affil= affil-num=3 en-affil=Department of Preventive Medicine Feinberg School of Medicine, Northwestern University kn-affil= affil-num=4 en-affil=Department of Breast and Endocrine Surgery, Akita University Hospital kn-affil= affil-num=5 en-affil=Department of Breast Surgical Oncology, Social Medical Corporation Hakuaikai Sagara Hospital kn-affil= affil-num=6 en-affil=Department of Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital of JFCR kn-affil= affil-num=7 en-affil=Department of Breast Surgery, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Breast Surgical Oncology, National Center for Global Health and Medicine kn-affil= affil-num=9 en-affil=Department of Breast Surgery, Kansai Medical University Hospital kn-affil= affil-num=10 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=13 en-affil=Department of Breast Cancer, Gunma Prefectural Cancer Center kn-affil= affil-num=14 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=FACT-B kn-keyword=FACT-B en-keyword=FACT-B+4 kn-keyword=FACT-B+4 en-keyword=QOL kn-keyword=QOL END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=6 article-no= start-page=388.e1 end-page=388.e14 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical effects of granulocyte colony-stimulating factor administration and the timing of its initiation on allogeneic hematopoietic cell transplantation outcomes for myelodysplastic syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Granulocyte colony-stimulating factor (G-CSF) accelerates neutrophil recovery after allogeneic hematopoietic cell transplantation (HCT). However, the optimal use of G-CSF and the timing of its initiation after allogeneic HCT for myelodysplastic syndrome (MDS) according to graft type have not been determined. This retrospective study aimed to investigate the effects of using G-CSF administration and the timing of its initiation on transplant outcomes in adult patients with MDS undergoing allogeneic HCT. Using Japanese registry data, we retrospectively investigated the effects of G-CSF administration and the timing of its initiation on transplant outcomes among 4140 adults with MDS after bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), or single-unit cord blood transplantation (CBT) between 2013 and 2022. Multivariate analysis showed that early (days 0 to 4) and late (days 5 to 10) G-CSF administration significantly accelerated neutrophil recovery compared with no G-CSF administration following BMT, PBSCT, and CBT, but there was no benefit of early G-CSF initiation for early neutrophilic recovery regardless of graft type. Late G-CSF initiation was significantly associated with a higher risk of overall chronic GVHD following PBSCT (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.18 to 2.24; P = .002) and CBT (HR, 2.09; 95% CI, 1.21 to 3.60; P = .007) compared with no G-CSF administration. Late G-CSF initiation significantly improved OS compared with no G-CSF administration only following PBSCT (HR, 0.74; 95% CI, 0.58 to 0.94; P = .015). However, G-CSF administration and the timing of its initiation did not affect acute GVHD, relapse, or non-relapse mortality, irrespective of graft type. These results suggest that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT, but increased risk of overall chronic GVHD after PBSCT and CBT. However, the effect of early and late G-CSF initiation on transplant outcomes needs further study in adult patients with MDS. en-copyright= kn-copyright= en-aut-name=KonumaTakaaki en-aut-sei=Konuma en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiokaMachiko en-aut-sei=Fujioka en-aut-mei=Machiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FuseKyoko en-aut-sei=Fuse en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HosoiHiroki en-aut-sei=Hosoi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasamotoYosuke en-aut-sei=Masamoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UchidaNaoyuki en-aut-sei=Uchida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaMasatsugu en-aut-sei=Tanaka en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SawaMasashi en-aut-sei=Sawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishidaTetsuya en-aut-sei=Nishida en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshikawaJun en-aut-sei=Ishikawa en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakamaeHirohisa en-aut-sei=Nakamae en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HasegawaYuta en-aut-sei=Hasegawa en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OnizukaMakoto en-aut-sei=Onizuka en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MaedaTakeshi en-aut-sei=Maeda en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FukudaTakahiro en-aut-sei=Fukuda en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawamuraKoji en-aut-sei=Kawamura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KandaYoshinobu en-aut-sei=Kanda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhbikiMarie en-aut-sei=Ohbiki en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ItonagaHidehiro en-aut-sei=Itonaga en-aut-mei=Hidehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Hematology, Sasebo City General Hospital kn-affil= affil-num=3 en-affil=Faculty of Medicine, Department of Hematology, Endocrinology and Metabolism, Niigata University kn-affil= affil-num=4 en-affil=Department of Hematology/Oncology, Wakayama Medical University kn-affil= affil-num=5 en-affil=Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital kn-affil= affil-num=6 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=7 en-affil=Department of Hematology, Toranomon Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Kanagawa Cancer Center kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Anjo Kosei Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital kn-affil= affil-num=11 en-affil=Department of Hematology, Osaka International Cancer Institute kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Hematology, Hokkaido University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Tokai University School of Medicine kn-affil= affil-num=16 en-affil=Department of Hematology and oncology, Kurashiki Central Hospital kn-affil= affil-num=17 en-affil=Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital kn-affil= affil-num=18 en-affil=Department of Hematology, Tottori University Hospital kn-affil= affil-num=19 en-affil=Division of Hematology, Jichi Medical University kn-affil= affil-num=20 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=21 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=22 en-affil=Transfusion and Cell Therapy Unit, Nagasaki University Hospital kn-affil= en-keyword=Granulocyte colony-stimulating factor kn-keyword=Granulocyte colony-stimulating factor en-keyword=Graft-versus-host disease kn-keyword=Graft-versus-host disease en-keyword=Bone marrow transplantation kn-keyword=Bone marrow transplantation en-keyword=Peripheral blood stem cell transplantation kn-keyword=Peripheral blood stem cell transplantation en-keyword=Cord blood transplantation kn-keyword=Cord blood transplantation en-keyword=Myelodysplastic syndrome kn-keyword=Myelodysplastic syndrome END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=78 end-page=85 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Standardization of radiation therapy quality control system through mutual quality control based on failure mode and effects analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=The advancement of irradiation technology has increased the demand for quality control of radiation therapy equipment. Consequently, the number of quality control items and required personnel have also increased. However, differences in the proportion of qualified personnel to irradiation techniques have caused bias in quality control systems among institutions. To standardize the quality across institutions, researchers should conduct mutual quality control by analyzing the quality control data of one institution at another institution and comparing the results with those of their own institutions. This study uses failure mode and effects analysis (FMEA) to identify potential risks in 12 radiation therapy institutions, compares the results before and after implementation of mutual quality control, and examines the utility of mutual quality control in risk reduction. Furthermore, a cost-effectiveness factor is introduced into FMEA to evaluate the utility of mutual quality control. en-copyright= kn-copyright= en-aut-name=TanimotoYuki en-aut-sei=Tanimoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OitaMasataka en-aut-sei=Oita en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KoshiKazunobu en-aut-sei=Koshi en-aut-mei=Kazunobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshiwakiKiyoshi en-aut-sei=Ishiwaki en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HiramatsuFutoshi en-aut-sei=Hiramatsu en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SasakiToshihisa en-aut-sei=Sasaki en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IseHiroki en-aut-sei=Ise en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyagawaTakashi en-aut-sei=Miyagawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaedaTakeshi en-aut-sei=Maeda en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkahiraShinsuke en-aut-sei=Okahira en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HamaguchiTakashi en-aut-sei=Hamaguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawaguchiTatsuya en-aut-sei=Kawaguchi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FunadaNorihiro en-aut-sei=Funada en-aut-mei=Norihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamamotoShuhei en-aut-sei=Yamamoto en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HiroshigeAkira en-aut-sei=Hiroshige en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MukaiYuki en-aut-sei=Mukai en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YoshidaShohei en-aut-sei=Yoshida en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FujitaYoshiki en-aut-sei=Fujita en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=NakahiraAtsuki en-aut-sei=Nakahira en-aut-mei=Atsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HondaHirofumi en-aut-sei=Honda en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems, Department of Healthcare Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiology, NHO Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Radiology, NHO Iwakuni Medical Center kn-affil= affil-num=5 en-affil=Department of Radiology, NHO Hamada Medical Center kn-affil= affil-num=6 en-affil=Department of Radiology, NHO Higashi-Hiroshima Medical Center kn-affil= affil-num=7 en-affil=Department of Radiology, NHO Iwakuni Medical Center kn-affil= affil-num=8 en-affil=Department of Radiology, NHO Kanmon Medical Center kn-affil= affil-num=9 en-affil=Department of Radiology, NHO Kochi National Hospital kn-affil= affil-num=10 en-affil=Department of Radiology, NHO Yamaguchi-Ube Medical Center kn-affil= affil-num=11 en-affil=Department of Radiology, NHO Okayama Medical Center kn-affil= affil-num=12 en-affil=Department of Radiology, NHO Shikoku Medical Center for Children and Adults kn-affil= affil-num=13 en-affil=Department of Radiology, NHO Hamada Medical Center kn-affil= affil-num=14 en-affil=Department of Radiology, NHO Fukuyama Medical Center kn-affil= affil-num=15 en-affil=Department of Radiology, NHO Shikoku Cancer Center kn-affil= affil-num=16 en-affil=Department of Radiology, NHO Shikoku Cancer Center kn-affil= affil-num=17 en-affil=Department of Radiology, NHO Shikoku Cancer Center kn-affil= affil-num=18 en-affil=Department of Radiology, NHO Shikoku Cancer Center kn-affil= affil-num=19 en-affil=Department of Radiology, NHO Shikoku Cancer Center kn-affil= affil-num=20 en-affil=Department of Radiological Technology, Ehime University Hospital kn-affil= en-keyword=Radiation therapy kn-keyword=Radiation therapy en-keyword=Quality control kn-keyword=Quality control en-keyword=Failure mode and effects analysis kn-keyword=Failure mode and effects analysis en-keyword=Cost-effectiveness kn-keyword=Cost-effectiveness END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=9 article-no= start-page=1983 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250427 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Initial Bonding Performance to CAD/CAM Restorative Materials: The Impact of Stepwise Concentration Variation in 8-Methacryloxyoctyl Trimethoxy Silane and 3-Methacryloxypropyl Trimethoxy Silane on Feldspathic Ceramic, Lithium Disilicate Glass-Ceramic, and Polymer-Infiltrated Ceramic en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigated the effects of varying concentrations of two distinct silane agents, 8-methacryloxyoctyl trimethoxy silane (8-MOTS) and 3-methacryloxypropyl trimethoxy silane (γ-MPTS), on their initial bonding efficacy to feldspathic ceramic (FC), lithium disilicate glass-ceramic (LD) and polymer-infiltrated ceramic (PIC) specimens, in 10% increments for concentrations ranging from 10% to 40%. Shear bond strengths between the ceramic substrates and the luting material were assessed following 24 h incubation in distilled water. For FC, the median value of shear bond strength peaked at 20% of γ-MPTS (7.4 MPa), while 8-MOTS exhibited a concentration-dependent increase, reaching its highest value at 40% (13.1 MPa). For LD, γ-MPTS above 10% yielded similar strength median values (10.2 MPa), whereas 8-MOTS at 30% (15.8 MPa) and 40% (13.4 MPa) yielded higher strength values than at 10% (2.9 MPa) and 20% (4.1 MPa), with the highest median value exhibited at 30%. For PIC, both γ-MPTS and 8-MOTS demonstrated similarly low bond strength values which were not significantly different from the non-silane-treated specimens. When applied on silica-based FC and LD, silane revealed a concentration-dependent bonding effect, with 8-MOTS exhibiting superior bond strength to γ-MPTS. However, PIC, characterized by a high inorganic filler content, demonstrated limited bondability with both silanes. en-copyright= kn-copyright= en-aut-name=MaruoYukinori en-aut-sei=Maruo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuwaharaMiho en-aut-sei=Kuwahara en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IrieMasao en-aut-sei=Irie en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshizaneMai en-aut-sei=Yoshizane en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoTakuya en-aut-sei=Matsumoto en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AkiyamaKentaro en-aut-sei=Akiyama en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Prosthodontics, Okayama University kn-affil= affil-num=2 en-affil=Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Health Research Institute, National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=4 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School kn-affil= affil-num=6 en-affil=Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=silane coupling kn-keyword=silane coupling en-keyword=bond strength kn-keyword=bond strength en-keyword=ceramic kn-keyword=ceramic en-keyword=feldspathic kn-keyword=feldspathic en-keyword=lithium kn-keyword=lithium en-keyword=polymer-infiltrated ceramic kn-keyword=polymer-infiltrated ceramic en-keyword=CAD/CAM kn-keyword=CAD/CAM END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High-Resolution HPLC for Separating Peptide-Oligonucleotide Conjugates en-subtitle= kn-subtitle= en-abstract= kn-abstract=Peptide-oligonucleotide conjugates (POCs) are chimeric molecules that combine the specificity of oligonucleotides with the functionality of peptides, improving the delivery and therapeutic potential of nucleic acid-based drugs. However, the analysis of POCs, particularly those containing arginine-rich sequences, poses major challenges because of aggregation caused by electrostatic interactions. In this study, we developed an optimized high-performance liquid chromatography (HPLC) method for analyzing POCs. Using a conjugate of DNA and nona-arginine as a model compound, we systematically investigated the effects of various analytical parameters, including column type, column temperature, mobile-phase composition, and pH. A column packed with C18 resin with wide pores combined with butylammonium acetate as the ion-pairing reagent and an optimal column temperature of 80 degrees C provided superior peak resolution and sensitivity. The optimized conditions gave clear separation of POCs from unlinked oligonucleotides and enabled the detection of nucleic acid fragments lacking an alkyne moiety as a linkage part, which is critical for quality control. Our HPLC method is robust and reproducible and substantially reduces the complexity, time, and cost associated with the POC analysis. The method may improve the efficiency of quality control in the production of POCs, thereby supporting their development as promising therapeutic agents for clinical applications. en-copyright= kn-copyright= en-aut-name=NaganumaMiyako en-aut-sei=Naganuma en-aut-mei=Miyako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiGenichiro en-aut-sei=Tsuji en-aut-mei=Genichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AmiyaMisato en-aut-sei=Amiya en-aut-mei=Misato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiraiReira en-aut-sei=Hirai en-aut-mei=Reira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HiguchiYuki en-aut-sei=Higuchi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HataNaoko en-aut-sei=Hata en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NozawaSaoko en-aut-sei=Nozawa en-aut-mei=Saoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeDaishi en-aut-sei=Watanabe en-aut-mei=Daishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakajimaTaeko en-aut-sei=Nakajima en-aut-mei=Taeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=DemizuYosuke en-aut-sei=Demizu en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Organic Chemistry, National Institute of Health Sciences kn-affil= affil-num=2 en-affil=Division of Organic Chemistry, National Institute of Health Sciences kn-affil= affil-num=3 en-affil=YMC CO., LTD. kn-affil= affil-num=4 en-affil=YMC CO., LTD. kn-affil= affil-num=5 en-affil=YMC CO., LTD. kn-affil= affil-num=6 en-affil=YMC CO., LTD. kn-affil= affil-num=7 en-affil=YMC CO., LTD. kn-affil= affil-num=8 en-affil=Division of Organic Chemistry, National Institute of Health Sciences kn-affil= affil-num=9 en-affil=YMC CO., LTD. kn-affil= affil-num=10 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Division of Pharmaceutical Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=214 cd-vols= no-issue= article-no= start-page=32 end-page=41 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Medaka approach to evolutionary social neuroscience en-subtitle= kn-subtitle= en-abstract= kn-abstract=Previously, the integration of comparative biological and neuroscientific approaches has led to significant advancements in social neuroscience. This review highlights the potential and future directions of evolutionary social neuroscience research utilizing medaka fishes (the family Adrianichthyidae) including Japanese medaka (Oryzias latipes). We focus on medaka social cognitive capabilities and mate choice behavior, particularly emphasizing mate preference using visual cues. Medaka fishes are also advantageous due to their abundant genetic resources, extensive genomic information, and the relative ease of laboratory breeding and genetic manipulation. Here we present some research examples of both the conventional neuroscience approach and evolutionary approach involving medaka fishes and other species. We also discuss the prospects of uncovering the molecular and cellular mechanisms underlying the diversity of visual mate preference among species. Especially, we introduce that the single-cell transcriptome technology, particularly in conjunction with 'Adaptive Circuitry Census', is an innovative tool that bridges comparative biological methods and neuroscientific approaches. Evolutionary social neuroscience research using medaka has the potential to unveil fundamental principles in neuroscience and elucidate the mechanisms responsible for generating diversity in mating strategies. en-copyright= kn-copyright= en-aut-name=AnsaiSatoshi en-aut-sei=Ansai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Hiraki-KajiyamaTowako en-aut-sei=Hiraki-Kajiyama en-aut-mei=Towako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UedaRyutaro en-aut-sei=Ueda en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekiTakahide en-aut-sei=Seki en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YokoiSaori en-aut-sei=Yokoi en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatsumuraTakafumi en-aut-sei=Katsumura en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeuchiHideaki en-aut-sei=Takeuchi en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=3 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=4 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=5 en-affil=School of Pharmaceutical Sciences, Hokkaido University kn-affil= affil-num=6 en-affil=School of Medicine, Kitasato University kn-affil= affil-num=7 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= en-keyword=Evolutionary neuroscience kn-keyword=Evolutionary neuroscience en-keyword=Comparative neuroscience kn-keyword=Comparative neuroscience en-keyword=Medaka bioresource kn-keyword=Medaka bioresource en-keyword=Visual mate preference kn-keyword=Visual mate preference en-keyword=Sexual selection kn-keyword=Sexual selection en-keyword=Genetic manipulation kn-keyword=Genetic manipulation END start-ver=1.4 cd-journal=joma no-vol=2024 cd-vols= no-issue=12 article-no= start-page=135 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241217 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Elliptic virtual structure constants and generalizations of BCOV-Zinger formula to projective Fano hypersurfaces en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this paper, we propose a method for computing genus 1 Gromov-Witten invariants of Calabi-Yau and Fano projective hypersurfaces using the B-model. Our formalism is applicable to both Calabi-Yau and Fano cases. In the Calabi-Yau case, significant cancellation of terms within our formalism occurs, resulting in an alternative representation of the BCOV-Zinger formula for projective Calabi-Yau hypersurfaces. en-copyright= kn-copyright= en-aut-name=JinzenjiMasao en-aut-sei=Jinzenji en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuwataKen en-aut-sei=Kuwata en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Mathematics, Okayama University kn-affil= affil-num=2 en-affil=Department of General Education, National Institute of Technology, Kagawa College kn-affil= en-keyword=Nonperturbative Effects kn-keyword=Nonperturbative Effects en-keyword=String Duality kn-keyword=String Duality en-keyword=Topological Field Theories kn-keyword=Topological Field Theories en-keyword=Topological Strings kn-keyword=Topological Strings END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=1757 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Keratinocyte-driven dermal collagen formation in the axolotl skin en-subtitle= kn-subtitle= en-abstract= kn-abstract=Type I collagen is a major component of the dermis and is formed by dermal fibroblasts. The development of dermal collagen structures has not been fully elucidated despite the major presence and importance of the dermis. This lack of understanding is due in part to the opacity of mammalian skin and it has been an obstacle to cosmetic and medical developments. We reveal the process of dermal collagen formation using the highly transparent skin of the axolotl and fluorescent collagen probes. We clarify that epidermal cells, not dermal fibroblasts, contribute to dermal collagen formation. Mesenchymal cells (fibroblasts) play a role in modifying the collagen fibers already built by keratinocytes. We confirm that collagen production by keratinocytes is a widely conserved mechanism in other model organisms. Our findings warrant a change in the current consensus about dermal collagen formation and could lead to innovations in cosmetology and skin medication. en-copyright= kn-copyright= en-aut-name=OhashiAyaka en-aut-sei=Ohashi en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakamotoHirotaka en-aut-sei=Sakamoto en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurodaJunpei en-aut-sei=Kuroda en-aut-mei=Junpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoYohei en-aut-sei=Kondo en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KameiYasuhiro en-aut-sei=Kamei en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NonakaShigenori en-aut-sei=Nonaka en-aut-mei=Shigenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FurukawaSaya en-aut-sei=Furukawa en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoSakiya en-aut-sei=Yamamoto en-aut-mei=Sakiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatohAkira en-aut-sei=Satoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Frontier Biosciences, Osaka University kn-affil= affil-num=4 en-affil=Center for One Medicine Innovative Translational Research (COMIT), Nagoya University kn-affil= affil-num=5 en-affil=Laboratory for Biothermology, National Institute for Basic Biology kn-affil= affil-num=6 en-affil=The Graduate University for Advanced Studies (SOKENDAI) kn-affil= affil-num=7 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=3 article-no= start-page=32 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250307 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rapid development of naked malting barley germplasm through targeted mutagenesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Covered barley (Hordeum vulgare) has historically been preferred for malting, as the husk in this plant protects the embryo during harvest and acts as a filter during brewing. Naked barley, which is typically used as food, has the potential to be used in brewing due to recent technical advances, but the grains contain higher levels of β-glucan and polyphenols, which are undesirable in brewing. Introducing the naked trait into brewing cultivars through crossing is time-consuming due to the need to eliminate these undesirable traits. In this study, we rapidly developed naked barley that is potentially suitable for malting by introducing targeted mutations into Nudum (NUD) using CRISPR/Cas9-mediated targeted mutagenesis. The doubled haploid line ‘DH120366’, which was used as the parental line, was derived from a cross between two covered malting barley cultivars. We generated CRISPR/Cas9-mediated targeted mutagenized barley harboring mutations in NUD via Agrobacterium tumefaciens-mediated transformation and confirmed the presence of mosaic mutations in one individual from among 16 T0 transformants. We sowed T1 grains exhibiting the naked trait and sequenced the NUD gene in these T1 seedlings, identifying two types of mutations. Shotgun high-throughput whole-genome sequencing confirmed the absence of the transgene in at least one nud mutant line following k-mer-based analysis. Cultivation in a closed growth chamber revealed no significant differences in agronomic traits between the nud mutants and the wild type. This study demonstrates the feasibility of rapidly developing naked barley with potential use for malting and brewing by targeting only NUD via targeted mutagenesis. en-copyright= kn-copyright= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakaiHiroaki en-aut-sei=Sakai en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamaokaMika en-aut-sei=Hamaoka en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MunemoriHiromi en-aut-sei=Munemori en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AbeFumitaka en-aut-sei=Abe en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MeintsBrigid en-aut-sei=Meints en-aut-mei=Brigid kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HayesPatrick M. en-aut-sei=Hayes en-aut-mei=Patrick M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Research Center for Advanced Analysis, National Agriculture and Food Research Organization kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Institute of Crop Science, National Agriculture and Food Research Organization kn-affil= affil-num=6 en-affil=Department Crop and Soil Science, Oregon State University kn-affil= affil-num=7 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=8 en-affil=Department Crop and Soil Science, Oregon State University kn-affil= en-keyword=Hordeum vulgare kn-keyword=Hordeum vulgare en-keyword=Covered (hulled) kn-keyword=Covered (hulled) en-keyword=Naked (hull-less) kn-keyword=Naked (hull-less) en-keyword=Genome editing kn-keyword=Genome editing en-keyword=CRISPR/Cas9 kn-keyword=CRISPR/Cas9 en-keyword=Transformation amenability kn-keyword=Transformation amenability END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=2 article-no= start-page=235 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Distinct Infection Mechanisms of Rhizoctonia solani AG-1 IA and AG-4 HG-I+II in Brachypodium distachyon and Barley en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rhizoctonia solani is a basidiomycete phytopathogenic fungus that causes rapid necrosis in a wide range of crop species, leading to substantial agricultural losses worldwide. The species complex is divided into 13 anastomosis groups (AGs) based on hyphal fusion compatibility and further subdivided by culture morphology. While R. solani classifications were shown to be independent of host specificity, it remains unclear whether different R. solani isolates share similar virulence mechanisms. Here, we investigated the infectivity of Japanese R. solani isolates on Brachypodium distachyon and barley. Two isolates, AG-1 IA (from rice) and AG-4 HG-I+II (from cauliflower), infected leaves of both plants, but only AG-4 HG-I+II infected roots. B. distachyon accessions Bd3-1 and Gaz-4 and barley cultivar 'Morex' exhibited enhanced resistance to both isolates compared to B. distachyon Bd21 and barley cultivars 'Haruna Nijo' and 'Golden Promise'. During AG-1 IA infection, but not AG-4 HG-I+II infection, resistant Bd3-1 and Morex induced genes for salicylic acid (SA) and N-hydroxypipecolic acid (NHP) biosynthesis. Pretreatment with SA or NHP conferred resistance to AG-1 IA, but not AG-4 HG-I+II, in susceptible B. distachyon Bd21 and barley Haruna Nijo. On the leaves of susceptible Bd21 and Haruna Nijo, AG-1 IA developed extensive mycelial networks with numerous infection cushions, which are specialized infection structures well-characterized in rice sheath blight. In contrast, AG-4 HG-I+II formed dispersed mycelial masses associated with underlying necrosis. We propose that the R. solani species complex encompasses at least two distinct infection strategies: AG-1 IA exhibits a hemibiotrophic lifestyle, while AG-4 HG-I+II follows a predominantly necrotrophic strategy. en-copyright= kn-copyright= en-aut-name=MahadevanNiranjan en-aut-sei=Mahadevan en-aut-mei=Niranjan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FernandaRozi en-aut-sei=Fernanda en-aut-mei=Rozi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KouzaiYusuke en-aut-sei=Kouzai en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KohnoNatsuka en-aut-sei=Kohno en-aut-mei=Natsuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagaoReiko en-aut-sei=Nagao en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NyeinKhin Thida en-aut-sei=Nyein en-aut-mei=Khin Thida kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeMegumi en-aut-sei=Watanabe en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SakataNanami en-aut-sei=Sakata en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuiHidenori en-aut-sei=Matsui en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ToyodaKazuhiro en-aut-sei=Toyoda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IchinoseYuki en-aut-sei=Ichinose en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MochidaKeiichi en-aut-sei=Mochida en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NoutoshiYoshiteru en-aut-sei=Noutoshi en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Crop Stress Management Group, Division of Plant Molecular Regulation Research, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO) kn-affil= affil-num=4 en-affil=Faculty of Agriculture, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Agriculture, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=12 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=13 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=14 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Rhizoctonia solani species complex kn-keyword=Rhizoctonia solani species complex en-keyword=virulence mechanism kn-keyword=virulence mechanism en-keyword=infection behavior kn-keyword=infection behavior en-keyword=salicylic acid kn-keyword=salicylic acid en-keyword=N-hydroxypipecolic acid kn-keyword=N-hydroxypipecolic acid END start-ver=1.4 cd-journal=joma no-vol=96 cd-vols= no-issue=10 article-no= start-page=1241 end-page=1252 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric Castleman disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly (TAFRO) syndrome is a heterogeneous entity manifesting with a constellation of symptoms described above that can occur in the context of idiopathic multicentric Castleman disease (iMCD) as well as infectious diseases, malignancies, and rheumatologic disorders. So, iMCD-TAFRO is an aggressive subtype of iMCD with TAFRO syndrome and often hyper-vascularized lymph nodes. Since we proposed diagnostic criteria of iMCD-TAFRO in 2016, we have accumulated new insights on the disorder and additional cases have been reported worldwide. In this systematic review and cohort analysis, we established and validated a definition for iMCD-TAFRO. First, we searched PubMed and Japan Medical Abstracts Society databases using the keyword “TAFRO” to extract cases. Patients with possible systemic autoimmune diseases and hematologic malignancies were excluded. Our search identified 54 cases from 50 articles. We classified cases into three categories: (1) iMCD-TAFRO (TAFRO syndrome with lymph node histopathology consistent with iMCD), (2) possible iMCD-TAFRO (TAFRO syndrome with no lymph node biopsy performed and no other co-morbidities), and (3) TAFRO without iMCD or other co-morbidities (TAFRO syndrome with lymph node histopathology not consistent with iMCD or other comorbidities). Based on the findings, we propose an international definition requiring four clinical criteria (thrombocytopenia, anasarca, fever/hyperinflammatory status, organomegaly), renal dysfunction or characteristic bone marrow findings, and lymph node features consistent with iMCD. The definition was validated with an external cohort (the ACCELERATE Natural History Registry). The present international definition will facilitate a more precise and comprehensive approach to the diagnosis of iMCD-TAFRO. en-copyright= kn-copyright= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FajgenbaumDavid C. en-aut-sei=Fajgenbaum en-aut-mei=David C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PiersonSheila K. en-aut-sei=Pierson en-aut-mei=Sheila K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwakiNoriko en-aut-sei=Iwaki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawanoMitsuhiro en-aut-sei=Kawano en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraNaoya en-aut-sei=Nakamura en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IzutsuKoji en-aut-sei=Izutsu en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakeuchiKengo en-aut-sei=Takeuchi en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YoshizakiKazuyuki en-aut-sei=Yoshizaki en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OksenhendlerEric en-aut-sei=Oksenhendler en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=van RheeFrits en-aut-sei=van Rhee en-aut-mei=Frits kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Cytokine Storm Treatment & Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=3 en-affil=Center for Cytokine Storm Treatment & Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=4 en-affil=Hematology/Respiratory Medicine, Kanazawa University Graduate School of Medical Science kn-affil= affil-num=5 en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Rheumatology, Kanazawa University Graduate School of Medical Science kn-affil= affil-num=7 en-affil=Department of Pathology, Tokai University School of Medicine kn-affil= affil-num=8 en-affil=Department of Hematology, National Cancer Center Hospital kn-affil= affil-num=9 en-affil=Department of Pathology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=10 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Organic Fine Chemicals, Institute of Scientific and Industrial Research, Osaka University kn-affil= affil-num=14 en-affil=Department of Clinical Immunology, Hôpital Saint-Louis kn-affil= affil-num=15 en-affil=Myeloma Center, University of Arkansas for Medical Sciences kn-affil= affil-num=16 en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=121 cd-vols= no-issue=35 article-no= start-page=e2320189121 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240821 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Somatic mutations in tumor-infiltrating lymphocytes impact on antitumor immunity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immune checkpoint inhibitors (ICIs) exert clinical efficacy against various types of cancers by reinvigorating exhausted CD8+ T cells that can expand and directly attack cancer cells (cancer-specific T cells) among tumor-infiltrating lymphocytes (TILs). Although some reports have identified somatic mutations in TILs, their effect on antitumor immunity remains unclear. In this study, we successfully established 18 cancer-specific T cell clones, which have an exhaustion phenotype, from the TILs of four patients with melanoma. We conducted whole-genome sequencing for these T cell clones and identified various somatic mutations in them with high clonality. Among the somatic mutations, an SH2D2A loss-of-function frameshift mutation and TNFAIP3 deletion could activate T cell effector functions in vitro. Furthermore, we generated CD8+ T cell–specific Tnfaip3 knockout mice and showed that Tnfaip3 function loss in CD8+ T cell increased antitumor immunity, leading to remarkable response to PD-1 blockade in vivo. In addition, we analyzed bulk CD3+ T cells from TILs in additional 12 patients and identified an SH2D2A mutation in one patient through amplicon sequencing. These findings suggest that somatic mutations in TILs can affect antitumor immunity and suggest unique biomarkers and therapeutic targets. en-copyright= kn-copyright= en-aut-name=MukoharaFumiaki en-aut-sei=Mukohara en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwataKazuma en-aut-sei=Iwata en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UenoToshihide en-aut-sei=Ueno en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IkedaHideki en-aut-sei=Ikeda en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawaseKatsushige en-aut-sei=Kawase en-aut-mei=Katsushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SaekiYuka en-aut-sei=Saeki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawashimaShusuke en-aut-sei=Kawashima en-aut-mei=Shusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamashitaKazuo en-aut-sei=Yamashita en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawaharaYu en-aut-sei=Kawahara en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakamuraYasuhiro en-aut-sei=Nakamura en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Honobe-TabuchiAkiko en-aut-sei=Honobe-Tabuchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WatanabeHiroko en-aut-sei=Watanabe en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=DansakoHiromichi en-aut-sei=Dansako en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KawamuraTatsuyoshi en-aut-sei=Kawamura en-aut-mei=Tatsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SuzukiYutaka en-aut-sei=Suzuki en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HondaHiroaki en-aut-sei=Honda en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ManoHiroyuki en-aut-sei=Mano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KawazuMasahito en-aut-sei=Kawazu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University kn-affil= affil-num=8 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=9 en-affil=Division of Cell Therapy, Chiba Cancer Research Institute kn-affil= affil-num=10 en-affil=Division of Cell Therapy, Chiba Cancer Research Institute kn-affil= affil-num=11 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=13 en-affil=KOTAI Biotechnologies, Inc. kn-affil= affil-num=14 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=16 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=17 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=18 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=19 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=20 en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa kn-affil= affil-num=21 en-affil=Department of Pathology, Tokyo Women's Medical University kn-affil= affil-num=22 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=23 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University kn-affil= affil-num=24 en-affil=Division of Cell Therapy, Chiba Cancer Research Institute kn-affil= affil-num=25 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=cancer immunology kn-keyword=cancer immunology en-keyword=somatic mutation kn-keyword=somatic mutation en-keyword=T cell kn-keyword=T cell en-keyword=tumor-infiltrating lymphocytes kn-keyword=tumor-infiltrating lymphocytes END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=1 article-no= start-page=e70062 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trends in uptake of cancer screening among people with severe mental illness before and after the COVID-19 pandemic in Japan: A repeated cross-sectional study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim: The aim of this study was to investigate trends in cancer screening participation among people with severe mental illness (PSMI) from periods before and after the COVID-19 pandemic.
Methods: In this repeated cross-sectional study, we used anonymized datasets on municipal cancer screening participation among PSMI in Okayama City. The data covered fiscal year (FY) 2018 to FY2022; we used the municipal cancer screening database and Medical Payment for Services and Supports for Persons with Disabilities. PSMI were defined as those with schizophrenia or related psychotic disorders (F20-29) or bipolar disorder (F30 or F31), identified using International Classification of Diseases, Tenth Revision, codes. The analysis included men and women aged 40-69 years for colorectal and lung cancer screening; men and women aged 50-69 years for gastric cancer screening; women aged 40-69 years for breast cancer screening; and women aged 20-69 years for cervical cancer screening. Municipal cancer screening rates among PSMI were calculated for each FY.
Results: For all cancer types, cancer screening rates for PSMI in FY2020 (colorectal: 9.0%; lung: 11.6%; gastric: 4.9%; breast: 6.2%; and cervical: 6.1%) were lower than the rates in FY2019 (11.5%, 14.0%, 6.5%, 9.3%, and 8.3%, respectively). In FY2022, the rates (9.9%, 12.9%; 5.3%; 8.0%, and 6.9%, respectively) recovered, but remained low.
Conclusion: This study showed that cancer screening rates among PSMI were very low, both before and after the COVID-19 pandemic. Efforts to encourage participation in cancer screening in this population are urgently needed. en-copyright= kn-copyright= en-aut-name=YamadaYuto en-aut-sei=Yamada en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakayaNaoki en-aut-sei=Nakaya en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtsukiKoji en-aut-sei=Otsuki en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimazuTaichi en-aut-sei=Shimazu en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimoriMaiko en-aut-sei=Fujimori en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HinotsuShiro en-aut-sei=Hinotsu en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagoshiKiwamu en-aut-sei=Nagoshi en-aut-mei=Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchitomiYosuke en-aut-sei=Uchitomi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=InagakiMasatoshi en-aut-sei=Inagaki en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=4 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= affil-num=5 en-affil=Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=6 en-affil=Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=7 en-affil=Department of Biostatistics and Data Management, Sapporo Medical University kn-affil= affil-num=8 en-affil=Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University kn-affil= affil-num=9 en-affil=Department of Cancer Survivorship and Digital Medicine, The Jikei University School of Medicine kn-affil= affil-num=10 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= en-keyword=bipolar disorder kn-keyword=bipolar disorder en-keyword=cancer screening kn-keyword=cancer screening en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=healthcare disparities kn-keyword=healthcare disparities en-keyword=schizophrenia kn-keyword=schizophrenia END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=3267 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250125 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel treatment strategy targeting interleukin-6 induced by cancer associated fibroblasts for peritoneal metastasis of gastric cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer-associated fibroblasts (CAFs) are a crucial component in the tumor microenvironment (TME) of peritoneal metastasis (PM), where they contribute to tumor progression and metastasis via secretion of interleukin-6 (IL-6). Here, we investigated the role of IL-6 in PM of gastric cancer (GC) and assessed whether anti-IL-6 receptor antibody (anti-IL-6R Ab) could inhibit PM of GC. We conducted immunohistochemical analysis of IL-6 and alpha-smooth muscle (alpha-SMA) expressions in clinical samples of GC and PM, and investigated the interactions between CAFs and GC cells in vitro. Anti-tumor effects of anti-IL-6R Ab on PM of GC were investigated in an orthotopic murine PM model. IL-6 expression was significantly correlated with alpha-SMA expression in clinical samples of GC, and higher IL-6 expression in the primary tumor was associated with poor prognosis of GC. Higher IL-6 and alpha-SMA expressions were also observed in PM of GC. In vitro, differentiation of fibroblasts into CAFs and chemoresistance were observed in GC cells cocultured with fibroblasts. Anti-IL-6R Ab inhibited the progression of PM in GC cells cocultured with fibroblasts in the orthotopic mouse model but could not inhibit the progression of PM consisting of GC cells alone. IL-6 expression in the TME was associated with poor prognosis of GC, and CAFs were associated with establishment and progression of PM via IL-6. Anti-IL-6R Ab could inhibit PM of GC by the blockade of IL-6 secreted by CAFs, which suggests its therapeutic potential for PM of GC. en-copyright= kn-copyright= en-aut-name=MitsuiEma en-aut-sei=Mitsui en-aut-mei=Ema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkuraTomohiro en-aut-sei=Okura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UneYuta en-aut-sei=Une en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiwakiNoriyuki en-aut-sei=Nishiwaki en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhtsukaJunko en-aut-sei=Ohtsuka en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhkiRieko en-aut-sei=Ohki en-aut-mei=Rieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute kn-affil= affil-num=12 en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Peritoneal metastasis kn-keyword=Peritoneal metastasis en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=Interleukin-6 kn-keyword=Interleukin-6 en-keyword=Cancer-associated fibroblasts kn-keyword=Cancer-associated fibroblasts en-keyword=Interleukin-6 receptor antibody kn-keyword=Interleukin-6 receptor antibody END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=1 article-no= start-page=4 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Differentially Expressed Nedd4-binding Protein Ndfip1 Protects Neurons Against Methamphetamine-induced Neurotoxicity en-subtitle= kn-subtitle= en-abstract= kn-abstract=To identify factors involved in methamphetamine (METH) neurotoxicity, we comprehensively searched for genes which were differentially expressed in mouse striatum after METH administration using differential display (DD) reverse transcription-PCR method and sequent single-strand conformation polymorphism analysis, and found two DD cDNA fragments later identified as mRNA of Nedd4 (neural precursor cell expressed developmentally downregulated 4) WW domain-binding protein 5 (N4WBP5), later named Nedd4 family-interacting protein 1 (Ndfip1). It is an adaptor protein for the binding between Nedd4 of ubiquitin ligase (E3) and target substrate protein for ubiquitination. Northern blot analysis confirmed drastic increases in Ndfip1 mRNA in the striatum after METH injections, and in situ hybridization histochemistry showed that the mRNA expression was increased in the hippocampus and cerebellum at 2 h-2 days, in the cerebral cortex and striatum at 18 h-2 days after single METH administration. The knockdown of Ndfip1 expression with Ndfip1 siRNA significantly aggravated METH-induced neurotoxicity in the cultured monoaminergic neuronal cells. These results suggest that drastic increases in Ndfip1 mRNA is compensatory reaction to protect neurons against METH-induced neurotoxicity. en-copyright= kn-copyright= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=CadetJean Lud en-aut-sei=Cadet en-aut-mei=Jean Lud kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Molecular Neuropsychiatry Section, Intramural Research Program, NIH/ NIDA kn-affil= en-keyword=Methamphetamine kn-keyword=Methamphetamine en-keyword=Neurotoxicity kn-keyword=Neurotoxicity en-keyword=Nedd4 kn-keyword=Nedd4 en-keyword=Ndfip1 kn-keyword=Ndfip1 en-keyword=Differential display kn-keyword=Differential display END start-ver=1.4 cd-journal=joma no-vol=125 cd-vols= no-issue= article-no= start-page=106672 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways en-subtitle= kn-subtitle= en-abstract= kn-abstract=Resveratrol, a polyphenol found in grapes and peanuts, is known for diverse biological activities, yet its effects on dermal hyperpigmentation (so-called dark spots) remain unexplored. We investigated resveratrol's ability to enhance melanosomal degradation in human dermal fibroblasts. At concentrations of 25-50 mu M, resveratrol increased autophagy as measured by microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I ratio and enhanced lysosomal activity as assessed by a lysosomal activity reporter system. RNA sequencing revealed upregulation of lysosomal and autophagy-related genes, including cathepsins. Furthermore, reporter assays showed resveratrol's activation of antioxidant response via nuclear factor erythroid 2-related factor 2 (NRF2)mediated, leading to upregulation of transcription factor EB/transcription factor E3 (TFEB/TFE3), master regulators of lysosomal function. In fibroblasts pre-loaded with melanosomes, resveratrol reduced melanosome content compared to control by day 3. The findings reveal the activation of interconnected autophagy, lysosomal, and antioxidant pathways by resveratrol, suggesting potential applications in functional foods targeting dermal hyperpigmentation. en-copyright= kn-copyright= en-aut-name=OkamotoSaki en-aut-sei=Okamoto en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KakimaruSaya en-aut-sei=Kakimaru en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KoreishiMayuko en-aut-sei=Koreishi en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoMika en-aut-sei=Sakamoto en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraYoshimasa en-aut-sei=Nakamura en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AndoHideya en-aut-sei=Ando en-aut-mei=Hideya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujinoYoshio en-aut-sei=Tsujino en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=National Institute of Genetics, ROIS kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Applied Chemistry and Biotechnology, Okayama University of Science kn-affil= affil-num=7 en-affil=Graduate School of Science, Technology, and Innovation, Kobe University kn-affil= affil-num=8 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=Antioxidant kn-keyword=Antioxidant en-keyword=Lysosomes kn-keyword=Lysosomes en-keyword=Autophagy kn-keyword=Autophagy en-keyword=Resveratrol kn-keyword=Resveratrol en-keyword=Skin fibroblasts kn-keyword=Skin fibroblasts en-keyword=Bioactive compounds kn-keyword=Bioactive compounds END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=29 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Three-Class Annotation Method Improves the AI Detection of Early-Stage Osteosarcoma on Plain Radiographs: A Novel Approach for Rare Cancer Diagnosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Developing high-performance artificial intelligence (AI) models for rare diseases is challenging owing to limited data availability. This study aimed to evaluate whether a novel three-class annotation method for preparing training data could enhance AI model performance in detecting osteosarcoma on plain radiographs compared to conventional single-class annotation. Methods: We developed two annotation methods for the same dataset of 468 osteosarcoma X-rays and 378 normal radiographs: a conventional single-class annotation (1C model) and a novel three-class annotation method (3C model) that separately labeled intramedullary, cortical, and extramedullary tumor components. Both models used identical U-Net-based architectures, differing only in their annotation approaches. Performance was evaluated using an independent validation dataset. Results: Although both models achieved high diagnostic accuracy (AUC: 0.99 vs. 0.98), the 3C model demonstrated superior operational characteristics. At a standardized cutoff value of 0.2, the 3C model maintained balanced performance (sensitivity: 93.28%, specificity: 92.21%), whereas the 1C model showed compromised specificity (83.58%) despite high sensitivity (98.88%). Notably, at the 25th percentile threshold, both models showed identical false-negative rates despite significantly different cutoff values (3C: 0.661 vs. 1C: 0.985), indicating the ability of the 3C model to maintain diagnostic accuracy at substantially lower thresholds. Conclusions: This study demonstrated that anatomically informed three-class annotation can enhance AI model performance for rare disease detection without requiring additional training data. The improved stability at lower thresholds suggests that thoughtful annotation strategies can optimize the AI model training, particularly in contexts where training data are limited. en-copyright= kn-copyright= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaharaRyuichi en-aut-sei=Nakahara en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaYujiro en-aut-sei=Otsuka en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamuraYusuke en-aut-sei=Nakamura en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkutaKunihiro en-aut-sei=Ikuta en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OsakiShuhei en-aut-sei=Osaki en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HironariTamiya en-aut-sei=Hironari en-aut-mei=Tamiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiwaShinji en-aut-sei=Miwa en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhshikaShusa en-aut-sei=Ohshika en-aut-mei=Shusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishimuraShunji en-aut-sei=Nishimura en-aut-mei=Shunji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KaharaNaoaki en-aut-sei=Kahara en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Medical Information and Assistive Technology Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiology, Juntendo University School of Medicine kn-affil= affil-num=4 en-affil=Plusman LCC kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Graduate School of Medicine, Nagoya University kn-affil= affil-num=6 en-affil=Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital kn-affil= affil-num=7 en-affil=Department of Musculoskeletal Oncology Service, Osaka International Cancer Institute kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Kanazawa University Graduate School of Medical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Kindai University Hospital kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery, Mizushima Central Hospital kn-affil= affil-num=12 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=osteosarcoma kn-keyword=osteosarcoma en-keyword=medical image annotation kn-keyword=medical image annotation en-keyword=anatomical annotation method kn-keyword=anatomical annotation method en-keyword=rare cancer kn-keyword=rare cancer END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=52 article-no= start-page=35202 end-page=35213 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bright Quantum-Grade Fluorescent Nanodiamonds en-subtitle= kn-subtitle= en-abstract= kn-abstract=Optically accessible spin-active nanomaterials are promising as quantum nanosensors for probing biological samples. However, achieving bioimaging-level brightness and high-quality spin properties for these materials is challenging and hinders their application in quantum biosensing. Here, we demonstrate bright fluorescent nanodiamonds (NDs) containing 0.6–1.3-ppm negatively charged nitrogen-vacancy (NV) centers by spin-environment engineering via enriching spin-less 12C-carbon isotopes and reducing substitutional nitrogen spin impurities. The NDs, readily introduced into cultured cells, exhibited improved optically detected magnetic resonance (ODMR) spectra; peak splitting (E) was reduced by 2–3 MHz, and microwave excitation power required was 20 times lower to achieve a 3% ODMR contrast, comparable to that of conventional type-Ib NDs. They show average spin-relaxation times of T1 = 0.68 ms and T2 = 3.2 μs (1.6 ms and 5.4 μs maximum) that were 5- and 11-fold longer than those of type-Ib, respectively. Additionally, the extended T2 relaxation times of these NDs enable shot-noise-limited temperature measurements with a sensitivity of approximately 0.28K/√Hz. The combination of bulk-like NV spin properties and enhanced fluorescence significantly improves the sensitivity of ND-based quantum sensors for biological applications. en-copyright= kn-copyright= en-aut-name=OshimiKeisuke en-aut-sei=Oshimi en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshiwataHitoshi en-aut-sei=Ishiwata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakashimaHiromu en-aut-sei=Nakashima en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MandićSara en-aut-sei=Mandić en-aut-mei=Sara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiHina en-aut-sei=Kobayashi en-aut-mei=Hina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TeramotoMinori en-aut-sei=Teramoto en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujiHirokazu en-aut-sei=Tsuji en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishibayashiYoshiki en-aut-sei=Nishibayashi en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShikanoYutaka en-aut-sei=Shikano en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AnToshu en-aut-sei=An en-aut-mei=Toshu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiwaraMasazumi en-aut-sei=Fujiwara en-aut-mei=Masazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=The National Institutes for Quantum Science and Technology (QST), Institute for Quantum Life Science (iQLS) kn-affil= affil-num=3 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Advanced Materials Laboratory, Sumitomo Electric Industries, Ltd. kn-affil= affil-num=7 en-affil=Advanced Materials Laboratory, Sumitomo Electric Industries, Ltd. kn-affil= affil-num=8 en-affil=Advanced Materials Laboratory, Sumitomo Electric Industries, Ltd. kn-affil= affil-num=9 en-affil=Institute of Systems and Information Engineering, University of Tsukuba kn-affil= affil-num=10 en-affil=School of Materials Science, Japan Advanced Institute of Science and Technology kn-affil= affil-num=11 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= en-keyword=nanodiamonds kn-keyword=nanodiamonds en-keyword=nitrogen-vacancy centers kn-keyword=nitrogen-vacancy centers en-keyword=spins kn-keyword=spins en-keyword=spin-relaxation times kn-keyword=spin-relaxation times en-keyword=quantum biosensor kn-keyword=quantum biosensor en-keyword=cellular probes kn-keyword=cellular probes END start-ver=1.4 cd-journal=joma no-vol=222 cd-vols= no-issue= article-no= start-page=115374 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Environmental water in Kolkata is suitable for the survival of Vibrio cholerae O1 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Many patients with cholera emerge in Kolkata, India throughout the year. Such emergency indicates that cholera toxin-producing Vibrio cholerae O1 (toxigenic V. cholerae O1) are widespread in Kolkata. This suggests that the suitable conditions for replication of toxigenic V. cholerae O1 is provided in Kolkata. In previous studies, we found that the replication rate of toxigenic V. cholerae O1 is low in the low ionic aqueous solution. Then we measured the ion concentration in the environmental water of Kolkata. As a control, we measured them in Japanese environmental water. The ion concentration in the environmental water of Kolkata was significantly high. Then, we examined the survival of toxigenic V. cholerae O1 in groundwater from Kolkata and found that V. cholerae O1 survive for long time in the solution but not in the solution diluted with Milli Q water. In addition, we found that V. cholerae O1 proliferated in environmental water of Kolkata to which a small amount of nutrient was added, but did not grow in the environmental water diluted with water to which the same amount of nutrient was added. These results indicate that the environmental water from Kolkata is suitable for survival of V. cholerae O1. en-copyright= kn-copyright= en-aut-name=TakahashiEizo en-aut-sei=Takahashi en-aut-mei=Eizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitaharaKei en-aut-sei=Kitahara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChowdhuryGoutam en-aut-sei=Chowdhury en-aut-mei=Goutam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MukhopadhyayAsish K. en-aut-sei=Mukhopadhyay en-aut-mei=Asish K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DuttaShanta en-aut-sei=Dutta en-aut-mei=Shanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OchiSadayuki en-aut-sei=Ochi en-aut-mei=Sadayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoKeinosuke en-aut-sei=Okamoto en-aut-mei=Keinosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Collaborative Research Center of Okayama University for Infectious Diseases in India kn-affil= affil-num=2 en-affil=Collaborative Research Center of Okayama University for Infectious Diseases in India kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences of Okayama University kn-affil= affil-num=4 en-affil=National Institute of Cholera and Enteric Diseases kn-affil= affil-num=5 en-affil=National Institute of Cholera and Enteric Diseases kn-affil= affil-num=6 en-affil=National Institute of Cholera and Enteric Diseases kn-affil= affil-num=7 en-affil=Department of Health Pharmacy, Yokohama University of Pharmacy kn-affil= affil-num=8 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences of Okayama University kn-affil= en-keyword=Environmental water kn-keyword=Environmental water en-keyword=Ion kn-keyword=Ion en-keyword=Prevalence kn-keyword=Prevalence en-keyword=Survival kn-keyword=Survival en-keyword=Vibrio cholerae kn-keyword=Vibrio cholerae END start-ver=1.4 cd-journal=joma no-vol=145 cd-vols= no-issue=8 article-no= start-page=881 end-page=896 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oral Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-versus-host Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated antigen-presenting cells, thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increase in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD. en-copyright= kn-copyright= en-aut-name=KambaraYui en-aut-sei=Kambara en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoAkira en-aut-sei=Yamamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KunihiroMari en-aut-sei=Kunihiro en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OyamaTadashi en-aut-sei=Oyama en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TeraoToshiki en-aut-sei=Terao en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoAyame en-aut-sei=Sato en-aut-mei=Ayame kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=PeltierDaniel en-aut-sei=Peltier en-aut-mei=Daniel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SogaYoshihiko en-aut-sei=Soga en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ReddyPavan en-aut-sei=Reddy en-aut-mei=Pavan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YoshinobuMaeda en-aut-sei=Yoshinobu en-aut-mei=Maeda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Medical School kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Microbiology and Genetics, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Simon Cancer Center, Indiana University School of Medicine kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=17 en-affil=Division of Blood Transfusion, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=19 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=20 en-affil=Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine kn-affil= affil-num=21 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=391 cd-vols= no-issue= article-no= start-page=158 end-page=176 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Magnesium isotope composition of volcanic rocks from cold and warm subduction zones: Implications for the recycling of subducted serpentinites and carbonates en-subtitle= kn-subtitle= en-abstract= kn-abstract=Magnesium (Mg) isotopes are regarded as a sensitive tracer to the contribution from subducted serpentinites and carbonates. However, the source, distribution, and controlling factors of the Mg isotope composition of arc magmas remain unclear. In this study, we investigated the intra-arc and inter-arc variations in Mg isotope compositions of volcanic rocks from two typical cold subduction zones [NE Japan (NEJ) and Izu arcs] and a typical hot subduction zone [SW Japan (SWJ) arc] to address the question. The volcanic rocks from the frontal-arc regions of NEJ and Izu have isotopically heavy Mg (δ26Mg = –0.20 to –0.08 ‰) compared to the mantle-like δ26Mg values of most of volcanic rocks from SWJ and the rear regions of NEJ and Izu arcs (–0.28 to –0.17 ‰). It is also worth noting that NEJ arc includes samples with δ26Mg values (–0.61 to –0.39 ‰) significantly lower than the mantle, but similar to the < 110 Ma intra-continental basalts from eastern China, which is the first observation in modern arc rocks. No obvious effects of post-eruptive alteration, fractional crystallization, partial melting, or the addition of silicate-rich sediment and oceanic crust components could be identified in the Mg isotope compositions of these volcanic rocks. By contrast, the correlations between the δ26Mg values and the proxy for serpentinite component (i.e., 11B/10B and Nb/B ratios) indicate that the component exerts a strong control on the Mg-isotopic signature of these arc rocks. Considering metamorphic reactions in subduction lithologies under P-T conditions postulated for these arcs, the variations in δ26Mg values of these arc magmas are unlikely to have been controlled by dehydration of serpentinites in subducted oceanic lithosphere (slab serpentinite). Instead, the high-δ26Mg values of frontal-arc rocks are delivered by the fluids from serpentinite formed in the lowermost part of the sub-arc mantle (mantle wedge serpentinite) in channelized flow. Comparatively, such a high-δ26Mg signature is invisible in volcanic rocks from rear-arc regions of NEJ and Izu, and the entire SWJ, suggesting that the major Mg carriers in subducted serpentinites (e.g., talc, chlorite, and serpentine) were broken down completely before subducted slabs reached the depth beneath these volcanoes. Moreover, the volcanic rocks with low δ26Mg values from the rear arc of NEJ are characterized by high La/Yb and U/Nb ratios as well as low Ti/Eu, Ti/Ti*, and Hf/Hf* ratios, suggesting the involvements of carbonates in their magma sources. The quantitative modeling suggests that < 20 % of sedimentary carbonate (dolomite) was recycled into their mantle source, revealing that Mg-rich carbonate could be incorporated into a deep mantle wedge at rear-arc depths of 150–400 km in subduction zones. en-copyright= kn-copyright= en-aut-name=ZhangWei en-aut-sei=Zhang en-aut-mei=Wei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitagawaHiroshi en-aut-sei=Kitagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuangFang en-aut-sei=Huang en-aut-mei=Fang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=CAS Key Laboratory of Crust-Mantle Materials and Environments, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= en-keyword=Magnesium isotopes kn-keyword=Magnesium isotopes en-keyword=Arc magmas kn-keyword=Arc magmas en-keyword=Mantle wedge serpentinite kn-keyword=Mantle wedge serpentinite en-keyword=Slab serpentinite kn-keyword=Slab serpentinite en-keyword=Carbonate recycle kn-keyword=Carbonate recycle END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=3-4 article-no= start-page=116 end-page=125 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Deep Reinforcement Learning Enabled Adaptive Virtual Machine Migration Control in Multi-Stage Information Processing Systems en-subtitle= kn-subtitle= en-abstract= kn-abstract=This paper tackles a Virtual Machine (VM) migration control problem to maximize the progress (accuracy) of information processing tasks in multi-stage information processing systems. The conventional methods for this problem are effective only for specific situations, such as when the system load is high. In this paper, in order to adaptively achieve high accuracy in various situations, we propose a VM migration method using a Deep Reinforcement Learning (DRL) algorithm. It is difficult to directly apply a DRL algorithm to the VM migration control problem because the size of the solution space of the problem dynamically changes according to the number of VMs staying in the system while the size of the agent’s action space is fixed in DRL algorithms. To cope with this difficulty, the proposed method divides the VM migration control problem into two problems: the problem of determining only the VM distribution (i.e., the proportion of the number of VMs deployed on each edge server) and the problem of determining the locations of all the VMs so that it follows the determined VM distribution. The former problem is solved by a DRL algorithm, and the latter by a heuristic method. This approach makes it possible to apply a DRL algorithm to the VM migration control problem because the VM distribution is expressed by a vector with a fixed number of dimensions and can be directly outputted by the agent. The simulation results confirm that our proposed method can adaptively achieve quasi-optimal accuracy in various situations with different link delays, types of the information processing tasks and the number of VMs. en-copyright= kn-copyright= en-aut-name=FukushimaYukinobu en-aut-sei=Fukushima en-aut-mei=Yukinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KoujitaniYuki en-aut-sei=Koujitani en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakaneKazutoshi en-aut-sei=Nakane en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TarutaniYuya en-aut-sei=Tarutani en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WuCelimuge en-aut-sei=Wu en-aut-mei=Celimuge kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JiYusheng en-aut-sei=Ji en-aut-mei=Yusheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YokohiraTokumi en-aut-sei=Yokohira en-aut-mei=Tokumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MuraseTutomu en-aut-sei=Murase en-aut-mei=Tutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Information Science Nagoya University kn-affil= affil-num=4 en-affil=Graduate School of Engineering Osaka University kn-affil= affil-num=5 en-affil=Graduate School of Informatics and Engineering The Univ. of Electro-Commun. kn-affil= affil-num=6 en-affil=Information Systems Architecture Research Division National Institute of Informatics kn-affil= affil-num=7 en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Information Science Nagoya University kn-affil= en-keyword=Multi-stage information processing system kn-keyword=Multi-stage information processing system en-keyword=VM migration control kn-keyword=VM migration control en-keyword=Deep reinforcement learning kn-keyword=Deep reinforcement learning en-keyword=Deep Deterministic Policy Gradient (DDPG) kn-keyword=Deep Deterministic Policy Gradient (DDPG) END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=48 end-page=53 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effectiveness of oral health care intervention for stroke patients following the introduction of Oral Health Assessment Tool en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim: This study aimed to evaluate the effectiveness of oral health assessment tools in facilitating oral health care interventions by dental care providers for acute stroke patients within 48 h of admission, following a reform of the nursing system.
Methods: Data were gathered from a retrospective cohort study conducted at a stroke center, comparing 10 months before and after the implementation of the reformed system, with a 2-month interval. Parameters assessed included stroke type, severity measured using the National Institutes of Health Stroke Scale, stroke history, stroke-related factors, number of teeth, hospitalization cost and duration, occurrence of fever and pneumonia, stroke treatment, days from admission to dental intervention, and intervention frequency.
Results: Implementation of the new system significantly reduced the time before dental intervention (P < 0.001), increased the frequency of interventions (P < 0.001), and allowed for the management of more severe cases (P = 0.007). However, there was a slight increase in the occurrence of fevers and the days of fever (P = 0.039 and P = 0.015, respectively). Multiple regression analysis showed that fever days were positively correlated with stroke severity and the number of days from admission to dental intervention (P < 0.001 and P = 0.013, respectively). Even after propensity score matching adjusting for stroke severity, these associations persisted. Additional multiple regression analysis was performed after this, but fever days were positively correlated with stroke severity and sex (P < 0.001 and P = 0.008, respectively), as well as with the presence of other factors affecting the occurrence of fever.
Conclusions: Although the frequency and duration of fevers increased slightly, this approach, incorporating oral health assessment tools, made it possible to provide early dental intervention, particularly for patients with severe strokes. Geriatr Gerontol Int 2025; 25: 48–53. en-copyright= kn-copyright= en-aut-name=MatsunagaKazuyuki en-aut-sei=Matsunaga en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Yoshida‐TsuboiAyaka en-aut-sei=Yoshida‐Tsuboi en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoharaKen en-aut-sei=Inohara en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaYasuko en-aut-sei=Yoshida en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakahamaKanako en-aut-sei=Nakahama en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SasakiKazuki en-aut-sei=Sasaki en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SoudaFumie en-aut-sei=Souda en-aut-mei=Fumie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TerasawaYuka en-aut-sei=Terasawa en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimoeYutaka en-aut-sei=Shimoe en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Takeuchi‐HatanakaKazu en-aut-sei=Takeuchi‐Hatanaka en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KohriyamaTatsuo en-aut-sei=Kohriyama en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Brain Attack Center, Ota Memorial Hospital kn-affil= affil-num=4 en-affil=Brain Attack Center, Ota Memorial Hospital kn-affil= affil-num=5 en-affil=Brain Attack Center, Ota Memorial Hospital kn-affil= affil-num=6 en-affil=Brain Attack Center, Ota Memorial Hospital kn-affil= affil-num=7 en-affil=Brain Attack Center, Ota Memorial Hospital kn-affil= affil-num=8 en-affil=Brain Attack Center, Ota Memorial Hospital kn-affil= affil-num=9 en-affil=Brain Attack Center, Ota Memorial Hospital kn-affil= affil-num=10 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=11 en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Pathophysiology – Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Brain Attack Center, Ota Memorial Hospital kn-affil= affil-num=14 en-affil=Department of Pathophysiology – Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=acute stroke kn-keyword=acute stroke en-keyword=dental intervention kn-keyword=dental intervention en-keyword=medical and dental cooperation kn-keyword=medical and dental cooperation en-keyword=oral health assessment tool kn-keyword=oral health assessment tool en-keyword=severity kn-keyword=severity END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=23 article-no= start-page=4089 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Frequency and Significance of Body Weight Loss During Immunochemotherapy in Patients with Advanced Non-Small Cell Lung Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Limited data are available on the frequency and significance of body weight loss during cancer therapy. This study investigated the frequency of patients who experienced body weight loss during immune checkpoint inhibitor (ICI) plus chemotherapy for advanced non-small cell lung cancer (NSCLC) and the impact of weight loss on treatment outcomes. Methods: Using the clinical data of 370 patients with NSCLC who received a combination of ICI and chemotherapy at 13 institutions, this study investigated the frequency of body weight loss > 5% during treatment and determined the impact of body weight loss on patient outcomes. Results: Of the 370 included patients, 141 (38.1%) lost more than 5% of their body weight during ICI plus chemotherapy (WL group). The 2-month landmark analysis showed that patients who experienced body weight loss of >5% during treatment had worse overall survival (OS) and progression-free survival (PFS) than those who did not (OS 14.0 and 31.1 months in the WL non-WL groups, respectively, p < 0.001; PFS 6.8 and 10.9 months in the WL non-WL groups, respectively, p = 0.002). Furthermore, a negative impact of body weight loss on survival was observed even in those who had obesity (body mass index [BMI] >= 25.0) at the start of therapy (OS 12.8 and 25.4 months in the WL non-WL groups, respectively, p < 0.001; PFS 5.7 and 10.7 months in the WL non-WL groups, respectively, p = 0.038). Conclusions: In conclusion, weight loss of >5% during ICI plus chemotherapy negatively influenced patient outcomes. Further and broader studies should investigate the role of nutritional status, specifically weight change and nutritional support, in responsiveness to ICI plus chemotherapy. en-copyright= kn-copyright= en-aut-name=TaokaMasataka en-aut-sei=Taoka en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokoyamaToshihide en-aut-sei=Yokoyama en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueKoji en-aut-sei=Inoue en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TamuraTomoki en-aut-sei=Tamura en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoAkiko en-aut-sei=Sato en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanoHirohisa en-aut-sei=Kano en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraKayo en-aut-sei=Nakamura en-aut-mei=Kayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawaiHaruyuki en-aut-sei=Kawai en-aut-mei=Haruyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OchiNobuaki en-aut-sei=Ochi en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IchikawaHirohisa en-aut-sei=Ichikawa en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AndoChihiro en-aut-sei=Ando en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OzeIsao en-aut-sei=Oze en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center kn-affil= affil-num=6 en-affil=Department of Internal Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Fukuyama City Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Japanese Red Cross Himeji Hospital kn-affil= affil-num=10 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=11 en-affil=Department of Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=12 en-affil=Department of General Internal Medicine 4 , Kawasaki Medical School kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Okayama Rosai Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, KKR Takamatsu Hospital kn-affil= affil-num=15 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=16 en-affil=Division of Cancer Information and Control, Aichi Cancer Center Research Institute kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=body weight loss kn-keyword=body weight loss en-keyword=immune checkpoint inhibitors kn-keyword=immune checkpoint inhibitors en-keyword=chemotherapy kn-keyword=chemotherapy END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue= article-no= start-page=1468230 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Perspectives of traditional herbal medicines in treating retinitis pigmentosa en-subtitle= kn-subtitle= en-abstract= kn-abstract=Medicinal plants, also known as herbs, have been discovered and utilized in traditional medical practice since prehistoric times. Medicinal plants have been proven rich in thousands of natural products that hold great potential for the development of new drugs. Previously, we reviewed the types of Chinese traditional medicines that a Tang Dynasty monk Jianzhen (Japanese: Ganjin) brought to Japan from China in 742. This article aims to review the origin of Kampo (Japanese traditional medicine), and to present the overview of neurodegenerative diseases and retinitis pigmentosa as well as medicinal plants in some depth. Through the study of medical history of the origin of Kampo, we found that herbs medicines contain many neuroprotective ingredients. It provides us a new perspective on extracting neuroprotective components from herbs medicines to treat neurodegenerative diseases. Retinitis pigmentosa (one of the ophthalmic neurodegenerative diseases) is an incurable blinding disease and has become a popular research direction in global ophthalmology. To date, treatments for retinitis pigmentosa are very limited worldwide. Therefore, we intend to integrate the knowledge and skills from different disciplines, such as medical science, pharmaceutical science and plant science, to take a new therapeutic approach to treat neurodegenerative diseases. In the future, we will use specific active ingredients extracted from medicinal plants to treat retinitis pigmentosa. By exploring the potent bioactive ingredients present in medicinal plants, a valuable opportunity will be offered to uncover novel approaches for the development of drugs which target for retinitis pigmentosa. en-copyright= kn-copyright= en-aut-name=LiuShihui en-aut-sei=Liu en-aut-mei=Shihui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuoChie en-aut-sei=Matsuo en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeTakumi en-aut-sei=Abe en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChenJinghua en-aut-sei=Chen en-aut-mei=Jinghua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SunChi en-aut-sei=Sun en-aut-mei=Chi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhaoQing en-aut-sei=Zhao en-aut-mei=Qing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Ophthalmology, University of Florida, College of Medicine kn-affil= affil-num=6 en-affil=Department of Ophthalmology and Visual Sciences, Washington University in St. Louis kn-affil= affil-num=7 en-affil=National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= en-keyword=retinitis pigmentosa kn-keyword=retinitis pigmentosa en-keyword=ophthalmology kn-keyword=ophthalmology en-keyword=botany kn-keyword=botany en-keyword=pharmacology kn-keyword=pharmacology en-keyword=medical history kn-keyword=medical history en-keyword=compound kn-keyword=compound en-keyword=drug discovery kn-keyword=drug discovery en-keyword=degenerative diseases kn-keyword=degenerative diseases END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue= article-no= start-page=58 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=2023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association and dose-response relationship between exposure to alcohol advertising media and current drinking: a nationwide cross-sectional study of Japanese adolescents en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Underage drinking is a public health concern. However, few studies have examined the association between alcoholic beverage advertising and underage drinking, particularly in countries with low underage drinking rates, such as Japan. Therefore, we aimed to investigate the relationship between exposure to advertising in various media and alcohol drinking among Japanese adolescents.
Methods: We conducted a cross-sectional study involving 15,683 adolescents (51% girls) using data from a nationwide lifestyle survey in 2021 among junior and senior high schools across Japan. Media types were websites, stores, and public transportation. We defined current drinking as alcohol consumption of ≥1 day in the 30 days preceding the survey. Multivariable logistic regression was used to examine the association between exposure to alcohol advertisements and current drinking, adjusting for sex, grades, school area, lifestyle (bedtime and having fun at school), and addictive behaviors (smoking status and parents’ alcohol consumption).
Results: The prevalence of current drinking was 2.2% (2.3% of boys and 2.0% of girls). Students who were exposed to any alcohol advertising media had higher odds of current drinking compared with those who were not (odds ratio, 1.48; 95% confidence interval [CI], 1.18–1.87). Students who were exposed to web, in-store, and public transportation advertisements had odds ratios of 1.44 (95% CI, 1.14–1.81), 1.62 (1.28–2.05), and 1.45 (1.06–1.98) of current drinking, respectively, compared with those who were not. The association of exposure to alcohol advertising media with the prevalence of current drinking was similar among boys and girls (all p for sex interaction >0.1), except for that of exposure to web advertisements; its association with current drinking was more pronounced in girls (p for sex interaction = 0.046). Exposure to a larger cumulative number of different alcohol advertising media was independently associated with a higher prevalence of current drinking among all students, boys, and girls (p-values for trend <0.001, 0.031, and <0.001, respectively; p for sex interaction = 0.085).
Conclusions: We found an association with a dose-response relationship between exposure to alcohol advertisements and current drinking among adolescents in junior and senior high schools across Japan. Our findings highlight the need for further advertising regulations to prevent underage drinking. en-copyright= kn-copyright= en-aut-name=YoshidaKeita en-aut-sei=Yoshida en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KandaHideyuki en-aut-sei=Kanda en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuwabaraYuki en-aut-sei=Kuwabara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KinjoAya en-aut-sei=Kinjo en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshimotoHisashi en-aut-sei=Yoshimoto en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItoTeruna en-aut-sei=Ito en-aut-mei=Teruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KasugaHideaki en-aut-sei=Kasuga en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MinobeRuriko en-aut-sei=Minobe en-aut-mei=Ruriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MaesatoHitoshi en-aut-sei=Maesato en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=JikeMaki en-aut-sei=Jike en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsumotoYuuki en-aut-sei=Matsumoto en-aut-mei=Yuuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OtsukaYuichiro en-aut-sei=Otsuka en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ItaniOsamu en-aut-sei=Itani en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KaneitaYoshitaka en-aut-sei=Kaneita en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HiguchiSusumu en-aut-sei=Higuchi en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OsakiYoneatsu en-aut-sei=Osaki en-aut-mei=Yoneatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=5 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=6 en-affil=Department of Family Medicine, General Practice and Community Health, Institute of Medicine, University of Tsukuba kn-affil= affil-num=7 en-affil=Department of Food and Nutrition, Koriyama Women’s University kn-affil= affil-num=8 en-affil=Department of Hygiene and Preventive Medicine, Fukushima Medical University kn-affil= affil-num=9 en-affil=National Institute of Alcoholism, Kurihama National Hospital kn-affil= affil-num=10 en-affil=National Institute of Alcoholism, Kurihama National Hospital kn-affil= affil-num=11 en-affil=Department of Food Science and Nutrition, Faculty of Life and Environmental Science, Showa Women’s University kn-affil= affil-num=12 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=13 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=14 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=15 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=16 en-affil=National Institute of Alcoholism, Kurihama National Hospital kn-affil= affil-num=17 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= en-keyword=Underage drinking kn-keyword=Underage drinking en-keyword=Alcohol kn-keyword=Alcohol en-keyword=Adolescents kn-keyword=Adolescents en-keyword=Advertisement kn-keyword=Advertisement END start-ver=1.4 cd-journal=joma no-vol=99 cd-vols= no-issue=2 article-no= start-page=563 end-page=574 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241027 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Therapeutic potential of 4-phenylbutyric acid against methylmercury-induced neuronal cell death in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Methylmercury (MeHg) is an environmental neurotoxin that induces damage to the central nervous system and is the causative agent in Minamata disease. The mechanisms underlying MeHg neurotoxicity remain largely unknown, and there is a need for effective therapeutic agents, such as those that target MeHg-induced endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), which is activated as a defense mechanism. We investigated whether intraperitoneal administration of the chemical chaperone, 4-phenylbutyric acid (4-PBA), at 120 mg/kg/day can alleviate neurotoxicity in the brains of mice administered 50 ppm MeHg in drinking water for 5 weeks. 4-PBA significantly reduced MeHg-induced ER stress, neuronal apoptosis, and neurological symptoms. Furthermore, 4-PBA was effective even when administered 2 weeks after the initiation of exposure to 30 ppm MeHg in drinking water. Our results strongly indicate that ER stress and the UPR are key processes involved in MeHg toxicity, and that 4-PBA is a novel therapeutic candidate for MeHg-induced neurotoxicity. en-copyright= kn-copyright= en-aut-name=MikiRyohei en-aut-sei=Miki en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomuraRyosuke en-aut-sei=Nomura en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IijimaYuta en-aut-sei=Iijima en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KubotaSho en-aut-sei=Kubota en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakasugiNobumasa en-aut-sei=Takasugi en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwawakiTakao en-aut-sei=Iwawaki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujimuraMasatake en-aut-sei=Fujimura en-aut-mei=Masatake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UeharaTakashi en-aut-sei=Uehara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Division of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University kn-affil= affil-num=7 en-affil=Department of International Affairs and Research, National Institute for Minamata Disease kn-affil= affil-num=8 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Methylmercury kn-keyword=Methylmercury en-keyword=Neuronal cell death kn-keyword=Neuronal cell death en-keyword=Endoplasmic reticulum stress kn-keyword=Endoplasmic reticulum stress en-keyword=Unfolded protein response kn-keyword=Unfolded protein response END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=20 article-no= start-page=1677 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241018 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Colossal Dielectric Constant of Nanocrystalline/Amorphous Homo-Composite BaTiO3 Films Deposited via Pulsed Laser Deposition Technique en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report the pulsed laser deposition (PLD) of nanocrystalline/amorphous homo-composite BaTiO3 (BTO) films exhibiting an unprecedented combination of a colossal dielectric constant (epsilon(r)) and extremely low dielectric loss (tan delta). By varying the substrate deposition temperature (T-d) over a wide range (300-800 degrees C), we identified T-d = 550 degrees C as the optimal temperature for growing BTO films with an epsilon(r) as high as similar to 3060 and a tan delta as low as 0.04 (at 20 kHz). High-resolution transmission electron microscopy revealed that the PLD-BTO films consist of BTO nanocrystals (similar to 20-30 nm size) embedded within an otherwise amorphous BTO matrix. The impressive dielectric behavior is attributed to the combination of highly crystallized small BTO nanograins, which amplify interfacial polarization, and the surrounding amorphous matrix, which effectively isolates the nanograins from charge carrier transport. Our findings could facilitate the development of next-generation integrated dielectric devices. en-copyright= kn-copyright= en-aut-name=KondoShinya en-aut-sei=Kondo en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MurakamiTaichi en-aut-sei=Murakami en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PichonLoick en-aut-sei=Pichon en-aut-mei=Loick kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Leblanc-LavoieJoel en-aut-sei=Leblanc-Lavoie en-aut-mei=Joel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TeranishiTakashi en-aut-sei=Teranishi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KishimotoAkira en-aut-sei=Kishimoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=El KhakaniKhakani, My Ali en-aut-sei=El Khakani en-aut-mei=Khakani, My Ali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Institut National de la Recherche Scientifique (INRS), Centre Énergie, Matériaux et Télécommunications kn-affil= affil-num=4 en-affil=Institut National de la Recherche Scientifique (INRS), Centre Énergie, Matériaux et Télécommunications kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Institut National de la Recherche Scientifique (INRS), Centre Énergie, Matériaux et Télécommunications kn-affil= en-keyword=BaTiO3 kn-keyword=BaTiO3 en-keyword=thin film kn-keyword=thin film en-keyword=colossal dielectric constant kn-keyword=colossal dielectric constant en-keyword=nanocrystalline/amorphous homo-composite kn-keyword=nanocrystalline/amorphous homo-composite en-keyword=pulsed laser deposition kn-keyword=pulsed laser deposition END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue= article-no= start-page=153285 end-page=153294 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Detecting Unintended Redirects to Malicious Websites on Android Devices Based on URL-Switching Interval en-subtitle= kn-subtitle= en-abstract= kn-abstract=Website clicks that redirect Android-phone users to malicious websites with fake virus alerts or phishing attacks are increasing exponentially. Although a uniform resource locator (URL) blocklist is considered a suitable countermeasure to such attacks, it is difficult to efficiently identify malicious websites. To the best of our knowledge, no research has focused on detecting attacks that redirect Android-phone users to malicious websites. Therefore, we propose a redirect-detection method that focuses on the URL bar-switching interval of Android-based Google Chrome browser. The proposed method, which can be easily installed as an Android application, uses the Android accessibility service to detect unintended redirects to malicious websites without collecting information about these websites in advance. This paper details the design, implementation, and evaluation results of the proposed application on an actual Android device. We determined the threshold values for the number of times the URL bar switches and the elapsed time to determine redirects to malicious websites for the proposed method. Based on the results, we investigated the causes of false-positive detection of redirects to benign websites and offer solutions on handling them. We also present the threshold values that can minimize the false positive and negative rates, as well as the detection accuracy of the proposed method based on these threshold values. Additionally, we present the evaluations results based on the access logs of actual users participating in the WarpDrive project experiment, which indicate that the proposed method minimizes false positives and successfully detects most redirects to malicious websites. en-copyright= kn-copyright= en-aut-name=YamauchiToshihiro en-aut-sei=Yamauchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OritoRintaro en-aut-sei=Orito en-aut-mei=Rintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EbisuKoji en-aut-sei=Ebisu en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoMasaya en-aut-sei=Sato en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Faculty of Computer Science and Systems Engineering, Okayama Prefectural University kn-affil= en-keyword=Android kn-keyword=Android en-keyword=accessibility services kn-keyword=accessibility services en-keyword=malicious websites kn-keyword=malicious websites en-keyword=web-based attacks kn-keyword=web-based attacks en-keyword=web security kn-keyword=web security END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue= article-no= start-page=142592 end-page=142605 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241001 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=MUSIC Spectrum Based Interference Detection, Localization, and Interference Arrival Prediction for mmWave IRS-MIMO System en-subtitle= kn-subtitle= en-abstract= kn-abstract=For a millimeter wave (mmWave) intelligent re-configurable surface (IRS)-MIMO system, if it can correctly detect the interference occurrence and their locations, the patterns of interference signal can be collected and learned using machine learning for the prediction of interference arrival. With the information of interference location and activity pattern, the capacity of the system can be largely improved using many techniques such as beamforming, interference cancellation, and transmission scheduling. This paper aims to detect interference occurrence using a low-complexity MUSIC (MUSIC: multiple signal classification) spectrum-based method, and then localize their sources for mmWave IRS-MIMO system. The MUSIC spectrum of wireless system can be regarded as somehow the 'signature' related to the signals transmitted from different users or interference. We utilize such property to detect the occurrence of interference, and then localize their sources in a low-complexity way. Finally, the pattern of interference occurrence can be learned to predict the interference arrival from the collected data. This paper also proposed an efficient probabilistic neural network (PNN)-based predictor for the interference arrival prediction and showed its prediction accuracy. From simulated results, our proposed method can achieve the correct results with the accuracy near to 100% when the fingerprint samples is over 10. In addition, the localization error can be within 1 m with more than 65% and 43% for Y-axis and X-axis, respectively. Finally, based on the results of the interference occurrence, the proposed PNN-based predictor for the interference arrival prediction can capture correctly the similar distribution function of the coming continuous idle status. en-copyright= kn-copyright= en-aut-name=HouYafei en-aut-sei=Hou en-aut-mei=Yafei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YanoKazuto en-aut-sei=Yano en-aut-mei=Kazuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugaNorisato en-aut-sei=Suga en-aut-mei=Norisato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WebberJulian en-aut-sei=Webber en-aut-mei=Julian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DennoSatoshi en-aut-sei=Denno en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakanoToshikazu en-aut-sei=Sakano en-aut-mei=Toshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Wave Engineering Laboratories, Advanced Telecommunications Research Institute International kn-affil= affil-num=3 en-affil=Wave Engineering Laboratories, Advanced Telecommunications Research Institute International kn-affil= affil-num=4 en-affil=Wave Engineering Laboratories, Advanced Telecommunications Research Institute International kn-affil= affil-num=5 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Wave Engineering Laboratories, Advanced Telecommunications Research Institute International kn-affil= en-keyword=Interference detection kn-keyword=Interference detection en-keyword=MUSIC spectrum kn-keyword=MUSIC spectrum en-keyword=interference localization kn-keyword=interference localization en-keyword=prediction of interference arrival kn-keyword=prediction of interference arrival en-keyword=probabilistic neural network kn-keyword=probabilistic neural network END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=9 article-no= start-page=1781 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Novel C-Terminal Truncated Bacteriocin Found by Comparison between Leuconostoc mesenteroides 406 and 213M0 Isolated from Mongolian Traditional Fermented Milk, Airag en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bacteriocins produced by lactic acid bacteria are known to be useful tools for food biopreservation and fermentation control. Leuconostoc mesenteroides subsp. mesenteroides 406 and 213M0 isolated from different samples of Mongolian traditional fermented milk, airag, had been reported to produce listericidal bacteriocin-like inhibitory substances with similar but slightly different properties. In this study, the antibacterial properties and the related gene sequences of both strains were compared, and then their bacteriocins were purified and identified. Strain 406 was superior to strain 213M0 in cell growth and antibacterial activity against many strains. However, the activity of 213M0 was stronger than that of 406 against a few strains. DNA sequencing revealed two and three plasmids in 406 and 213M0, respectively, and each one of them harbored an almost identical mesentericin Y105-B105 gene cluster. Removal of these plasmids resulted in a complete loss of activity, indicating that the antibacterial activity of both strains was generated by bacteriocins encoded on the plasmids. Mesentericins Y105 and B105 were purified from both cultures, and another novel bacteriocin, named mesentericin M, was identified from the 213M0 culture only. Its structural gene was coded on a 213M0 plasmid and, surprisingly, its C-terminal three amino acid residues were post-translationally cleaved. To our knowledge, this is the first report of a C-terminal truncated bacteriocin. In conclusion, the novel bacteriocin should be mainly responsible for the difference in antibacterial properties between the two strains. en-copyright= kn-copyright= en-aut-name=HasiqimugeChihiro en-aut-sei=Hasiqimuge en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HanoChihiro en-aut-sei=Hano en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ArakawaKensuke en-aut-sei=Arakawa en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaSaki en-aut-sei=Yoshida en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhaoJunliang en-aut-sei=Zhao en-aut-mei=Junliang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TohHidehiro en-aut-sei=Toh en-aut-mei=Hidehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MoritaHidetoshi en-aut-sei=Morita en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyamotoTaku en-aut-sei=Miyamoto en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Advanced Genomics Center, National Institute of Genetics kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=Leuconostoc mesenteroides kn-keyword=Leuconostoc mesenteroides en-keyword=antimicrobial peptide kn-keyword=antimicrobial peptide en-keyword=bacteriocin kn-keyword=bacteriocin en-keyword=Listeria monocytogenes kn-keyword=Listeria monocytogenes en-keyword=fermented milk kn-keyword=fermented milk en-keyword=biopreservation kn-keyword=biopreservation en-keyword=fermentation control kn-keyword=fermentation control en-keyword=post-translational modification kn-keyword=post-translational modification en-keyword=C-terminal cleavage kn-keyword=C-terminal cleavage END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=018003 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Design and performance of a gain calibration system for the POLARBEAR-2a receiver system at the Simons Array cosmic microwave background experiment en-subtitle= kn-subtitle= en-abstract= kn-abstract=We present an advanced system for calibrating the detector gain responsivity with a chopped thermal source for POLARBEAR-2a, which is the first receiver system of a cosmic microwave background (CMB) polarimetry experiment: the Simons Array. Intensity-to-polarization leakage due to calibration errors between detectors can be a significant source of systematic error for a polarization-sensitive experiment. To suppress this systematic uncertainty, POLARBEAR-2a calibrates the detector gain responsivities by observing a chopped thermal source before and after each period of science observations. The system includes a high-temperature ceramic heater that emits blackbody radiation covering a wide frequency range and an optical chopper to modulate the radiation signal. We discuss the experimental requirements of gain calibration and system design to calibrate POLARBEAR-2a. We evaluate the performance of our system during the early commissioning of the receiver system. This calibration system is promising for the future generation of CMB ground-based polarization observations. en-copyright= kn-copyright= en-aut-name=KanekoDaisuke en-aut-sei=Kaneko en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakatoriSayuri en-aut-sei=Takatori en-aut-mei=Sayuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasegawaMasaya en-aut-sei=Hasegawa en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HazumiMasashi en-aut-sei=Hazumi en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueYuki en-aut-sei=Inoue en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JeongOliver en-aut-sei=Jeong en-aut-mei=Oliver kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatayamaNobuhiko en-aut-sei=Katayama en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LeeAdrian T. en-aut-sei=Lee en-aut-mei=Adrian T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsudaFrederick en-aut-sei=Matsuda en-aut-mei=Frederick kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishinoHaruki en-aut-sei=Nishino en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SiritanasakPraween en-aut-sei=Siritanasak en-aut-mei=Praween kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SuzukiAritoki en-aut-sei=Suzuki en-aut-mei=Aritoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakakuraSatoru en-aut-sei=Takakura en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TomaruTakayuki en-aut-sei=Tomaru en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=High Energy Accelerator Research Organization, International Center for Quantum-field Measurement Systems for Studies of the Universe and Particles kn-affil= affil-num=2 en-affil=Okayama University, Research Institute for Interdisciplinary Science kn-affil= affil-num=3 en-affil=High Energy Accelerator Research Organization, International Center for Quantum-field Measurement Systems for Studies of the Universe and Particles kn-affil= affil-num=4 en-affil=High Energy Accelerator Research Organization, International Center for Quantum-field Measurement Systems for Studies of the Universe and Particles kn-affil= affil-num=5 en-affil=National Central University, Center for High Energy and High Field Physics, Department of Physics kn-affil= affil-num=6 en-affil=University of California, Department of Physics kn-affil= affil-num=7 en-affil=University of Tokyo, Kavli Institute for the Physics and Mathematics of the Universe kn-affil= affil-num=8 en-affil=University of California, Department of Physics kn-affil= affil-num=9 en-affil=Japan Aerospace Exploration Agency, Institute of Space and Astronautical Science kn-affil= affil-num=10 en-affil=The University of Tokyo, Graduate School of Science, Research Center for the Early Universe kn-affil= affil-num=11 en-affil=National Astronomical Research Institute of Thailand kn-affil= affil-num=12 en-affil=Lawrence Berkeley National Laboratory, Physics Division kn-affil= affil-num=13 en-affil=Kyoto University, Department of Physics, Faculty of Science kn-affil= affil-num=14 en-affil=National Astronomical Observatory of Japan, Gravitational Wave Project Office kn-affil= en-keyword=cosmic microwave background kn-keyword=cosmic microwave background en-keyword=gain calibrator kn-keyword=gain calibrator en-keyword=detector calibration kn-keyword=detector calibration en-keyword=transition edge sensor kn-keyword=transition edge sensor END start-ver=1.4 cd-journal=joma no-vol=115 cd-vols= no-issue=11 article-no= start-page=3660 end-page=3671 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of ENO-1 positive extracellular vesicles as a circulating biomarker for monitoring of Ewing sarcoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=The lack of circulating biomarkers for tumor monitoring is a major problem in Ewing sarcoma management. The development of methods for accurate tumor monitoring is required, considering the high recurrence rate of drug- resistant Ewing sarcoma. Here, we describe a sensitive analytical technique for tumor monitoring of Ewing sarcoma by detecting circulating extracellular vesicles secreted from Ewing sarcoma cells. Proteomic analysis of Ewing sarcoma cell-derived extracellular vesicles identi-fied 564 proteins prominently observed in extracellular vesicles from three Ewing sarcoma cell lines. Among these, CD99, SLC1A5, and ENO-1 were identified on extra-cellular vesicles purified from sera of patients with Ewing sarcoma before treatment but not on extracellular vesicles from those after treatment and healthy individuals. Notably, not only Ewing sarcoma-derived extracellular vesicles but also Ewing sar-coma cells demonstrated proteomic expression of CD99 and ENO-1 on their surface membranes. ENO-1(+)CD6(3+) extracellular vesicle detection was reduced after tumor resection while both CD99+CD63+ and ENO-1(+)CD6(3+) extracellular vesicles were detected in serum from Ewing sarcoma- bearing mice. Finally, the accuracy of liquid biopsy targeting these candidates was assessed using extracellular vesicles from the sera of patients with Ewing sarcoma. Elevated ENO-1+CD81+ extracellular vesicles in the serum of patients before treatments distinguished patients with Ewing sarcoma from healthy individuals with an area under the curve value of 0.92 (P< 0.001) and reflected the tumor burden in patients with Ewing sarcoma during multidisciplinary treatments. Collectively, circulating ENO-1(+)CD81(+) extracellular vesicle detection could represent a novel tool for tumor monitoring of Ewing sarcoma. en-copyright= kn-copyright= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UedaKoji en-aut-sei=Ueda en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwataShintaro en-aut-sei=Iwata en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoritaTakuya en-aut-sei=Morita en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KiyonoMasahiro en-aut-sei=Kiyono en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakedaKen en-aut-sei=Takeda en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshiokaYusuke en-aut-sei=Yoshioka en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OchiyaTakahiro en-aut-sei=Ochiya en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Cancer Precision Medicine Center, Japanese Foundation for Cancer Research kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Musculoskeletal Oncology, National Cancer Center Hospital kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Intelligent Orthopedic System, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University kn-affil= affil-num=12 en-affil=Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University kn-affil= affil-num=13 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=circulating biomarker kn-keyword=circulating biomarker en-keyword=Ewing sarcoma kn-keyword=Ewing sarcoma en-keyword=extracellular vesicles kn-keyword=extracellular vesicles en-keyword=liquid biopsy kn-keyword=liquid biopsy en-keyword=proteome kn-keyword=proteome END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=8 article-no= start-page=1835 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240812 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Surface Pre-Reacted Glass-Ionomer Eluate Suppresses Osteoclastogenesis through Downregulation of the MAPK Signaling Pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=Surface pre-reacted glass-ionomer (S-PRG) is a new bioactive filler utilized for the restoration of decayed teeth by its ability to release six bioactive ions that prevent the adhesion of dental plaque to the tooth surface. Since ionic liquids are reported to facilitate transepithelial penetration, we reasoned that S-PRG applied to root caries could impact the osteoclasts (OCs) in the proximal alveolar bone. Therefore, this study aimed to investigate the effect of S-PRG eluate solution on RANKL-induced OC-genesis and mineral dissolution in vitro. Using RAW264.7 cells as OC precursor cells (OPCs), TRAP staining and pit formation assays were conducted to monitor OC-genesis and mineral dissolution, respectively, while OC-genesis-associated gene expression was measured using quantitative real-time PCR (qPCR). Expression of NFATc1, a master regulator of OC differentiation, and the phosphorylation of MAPK signaling molecules were measured using Western blotting. S-PRG eluate dilutions at 1/200 and 1/400 showed no cytotoxicity to RAW264.7 cells but did significantly suppress both OC-genesis and mineral dissolution. The same concentrations of S-PRG eluate downregulated the RANKL-mediated induction of OCSTAMP and CATK mRNAs, as well as the expression of NFATc1 protein and the phosphorylation of ERK, JNK, and p38. These results demonstrate that S-PRG eluate can downregulate RANKL-induced OC-genesis and mineral dissolution, suggesting that its application to root caries might prevent alveolar bone resorption. en-copyright= kn-copyright= en-aut-name=ChandraJanaki en-aut-sei=Chandra en-aut-mei=Janaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraShin en-aut-sei=Nakamura en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShindoSatoru en-aut-sei=Shindo en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LeonElizabeth en-aut-sei=Leon en-aut-mei=Elizabeth kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CastellonMaria en-aut-sei=Castellon en-aut-mei=Maria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=PastoreMaria Rita en-aut-sei=Pastore en-aut-mei=Maria Rita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HeidariAlireza en-aut-sei=Heidari en-aut-mei=Alireza kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WitekLukasz en-aut-sei=Witek en-aut-mei=Lukasz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=CoelhoPaulo G. en-aut-sei=Coelho en-aut-mei=Paulo G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakatsukaToshiyuki en-aut-sei=Nakatsuka en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawaiToshihisa en-aut-sei=Kawai en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=2 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=4 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=5 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=6 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=7 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=8 en-affil=Biomaterials Division, NYU Dentistry kn-affil= affil-num=9 en-affil=Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami kn-affil= affil-num=10 en-affil=R&D Department, Shofu Inc. kn-affil= affil-num=11 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= en-keyword=S-PRG kn-keyword=S-PRG en-keyword=osteoclast kn-keyword=osteoclast en-keyword=hydroxyapatite kn-keyword=hydroxyapatite en-keyword=TRAP staining kn-keyword=TRAP staining en-keyword=bioactive filler kn-keyword=bioactive filler END start-ver=1.4 cd-journal=joma no-vol=115 cd-vols= no-issue=11 article-no= start-page=3695 end-page=3704 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High-quality expert annotations enhance artificial intelligence model accuracy for osteosarcoma X-ray diagnosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Primary malignant bone tumors, such as osteosarcoma, significantly affect the pediatric and young adult populations, necessitating early diagnosis for effective treatment. This study developed a high-performance artificial intelligence (AI) model to detect osteosarcoma from X-ray images using highly accurate annotated data to improve diagnostic accuracy at initial consultations. Traditional models trained on unannotated data have shown limited success, with sensitivities of approximately 60%–70%. In contrast, our model used a data-centric approach with annotations from an experienced oncologist, achieving a sensitivity of 95.52%, specificity of 96.21%, and an area under the curve of 0.989. The model was trained using 468 X-ray images from 31 osteosarcoma cases and 378 normal knee images with a strategy to maximize diversity in the training and validation sets. It was evaluated using an independent dataset of 268 osteosarcoma and 554 normal knee images to ensure generalizability. By applying the U-net architecture and advanced image processing techniques such as renormalization and affine transformations, our AI model outperforms existing models, reducing missed diagnoses and enhancing patient outcomes by facilitating earlier treatment. This study highlights the importance of high-quality training data and advocates a shift towards data-centric AI development in medical imaging. These insights can be extended to other rare cancers and diseases, underscoring the potential of AI in transforming diagnostic processes in oncology. The integration of this AI model into clinical workflows could support physicians in early osteosarcoma detection, thereby improving diagnostic accuracy and patient care. en-copyright= kn-copyright= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaharaRyuichi en-aut-sei=Nakahara en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaYujiro en-aut-sei=Otsuka en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamuraYusuke en-aut-sei=Nakamura en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HironariTamiya en-aut-sei=Hironari en-aut-mei=Tamiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KaharaNaoaki en-aut-sei=Kahara en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiwaShinji en-aut-sei=Miwa en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhshikaShusa en-aut-sei=Ohshika en-aut-mei=Shusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishimuraShunji en-aut-sei=Nishimura en-aut-mei=Shunji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IkutaKunihiro en-aut-sei=Ikuta en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OsakiShuhei en-aut-sei=Osaki en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Medical Information and Assistive Technology Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Radiology, Juntendo University School of Medicine kn-affil= affil-num=4 en-affil=Department of Radiology, Juntendo University School of Medicine kn-affil= affil-num=5 en-affil=Department of Musculoskeletal Oncology Service, Osaka International Cancer Institute kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Mizushima Central Hospital kn-affil= affil-num=7 en-affil= Department of Orthopedic Surgery, Kanazawa University Graduate School of Medical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Kindai University Hospital kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Musculoskeletal Oncology, National Cancer Center Hospital kn-affil= affil-num=12 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=clinical decision support kn-keyword=clinical decision support en-keyword=diagnostic imaging kn-keyword=diagnostic imaging en-keyword=image annotation kn-keyword=image annotation en-keyword=osteosarcoma detection kn-keyword=osteosarcoma detection END start-ver=1.4 cd-journal=joma no-vol=62 cd-vols= no-issue=5 article-no= start-page=897 end-page=900 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202409 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A randomized, open-label phase II study on the preventive effect of goshajinkigan against peripheral neuropathy induced by paclitaxel-containing chemotherapy: The OLCSG2101 study protocol en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Paclitaxel (PTX) is an essential cytotoxic anticancer agent and a standard treatment regimen component for various malignant tumors, including advanced unresectable non-small cell lung cancer, thymic cancer, and primary unknown cancers. However, chemotherapy-induced peripheral neuropathy (CIPN) caused by PTX is a significant adverse event that may lead to chemotherapy discontinuation and deterioration of the quality of life (QOL). Although treatment modalities such as goshajinkigan (GJG), pregabalin, and duloxetine are empirically utilized for CIPN, there is no established evidence for an agent as a preventive measure. We designed a randomized phase II trial (OLCSG2101) to investigate whether prophylactic GJG administration can prevent the onset of CIPN induced by PTX.
Methods: This study was designed as a two-arm, prospective, randomized, multicenter phase II trial. The patients will be randomly assigned to either the GJG prophylaxis arm (Arm A) or the GJG non-prophylaxis arm (Arm B), using cancer type (lung cancer or not) and age (<70 years or not) as adjustment factors. A total of 66 patients (33 in each arm) will be enrolled.
Discussion: The results of this study may contribute to better management of CIPN, which can enable the continuation of chemotherapy and maintenance of the patient's QOL.
Ethics and dissemination: Ethical approval was obtained from the certified review board of Okayama University (approval no. CRB21-005) on September 28, 2021. Results will be published in peer-reviewed journals and presented at national and international conferences.
Trial registration: Japan Registry of Clinical Trials (registration number jRCTs061210047). en-copyright= kn-copyright= en-aut-name=NakamuraNaoki en-aut-sei=Nakamura en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaTakaaki en-aut-sei=Tanaka en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatoYuka en-aut-sei=Kato en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OzeIsao en-aut-sei=Oze en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KozukiToshiyuki en-aut-sei=Kozuki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YokoyamaToshihide en-aut-sei=Yokoyama en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IchikawaHirohisa en-aut-sei=Ichikawa en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaraNaofumi en-aut-sei=Hara en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Center of Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Shikoku Cancer Center kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Kurashiki Central Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, KKR Takamatsu Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Iwakuni Clinical Center kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Okayama Rosai Hospital kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Center of Innovative Clinical Medicine, Okayama University Hospital kn-affil= en-keyword=Kampo kn-keyword=Kampo en-keyword=CIPN kn-keyword=CIPN en-keyword=prophylaxis kn-keyword=prophylaxis en-keyword=neuropathy kn-keyword=neuropathy en-keyword=taxane kn-keyword=taxane END start-ver=1.4 cd-journal=joma no-vol=38 cd-vols= no-issue=2 article-no= start-page=394 end-page=408 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200221 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The neurotoxicity of psychoactive phenethylamines “2C series” in cultured monoaminergic neuronal cell lines en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose The aim of this study was to evaluate the neurotoxicity of psychoactive abused 2,5-dimethoxy-substituted phenethylamines “2C series” in monoaminergic neurons.
Methods After the exposure to “2C series”, 2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7), 2,5-dimethoxy-4-isopropylthiophenethylamine (2C-T-4), 2,5-dimethoxy-4-ethylthiophenthylamine (2C-T-2), 2,5-dimethoxy-4-iodophenethylamine (2C-I) or 2,5-dimethoxy-4-chlorophenethylamine (2C-C), we examined their neurotoxicity, morphological changes, and effects of concomitant exposure to 3,4-methylenedioxymethamphetamine (MDMA) or methamphetamine (METH), using cultured neuronal dopaminergic CATH.a cells and serotonin-containing B65 cells.
Results Single dose exposure to “2C series” for 24 h showed significant cytotoxicity as increase in lactate dehydrogenase (LDH) release from both monoaminergic neurons: 2C-T-7, 2C-C (EC50; 100 µM) > 2C-T-2 (150 µM), 2C-T-4 (200 µM) > 2C-I (250 µM) in CATH.a cells and 2C-T-7, 2C-I (150 µM) > 2C-T-2 (250 µM) > 2C-C, 2C-T-4 (300 µM) in B65 cells. The “2C series”-induced neurotoxicity in both cells was higher than that of MDMA or METH (EC50: ≥ 1–2 mM). In addition, apoptotic morphological changes were observed at relatively lower concentrations of “2C series”. The concomitant exposure to non-toxic dose of MDMA or METH synergistically enhanced 2C series drugs-induced LDH release and apoptotic changes in B65 cells, but to a lesser extent in CATH.a cells. In addition, the lower dose of 2C-T-7, 2C-T-2 or 2C-I promoted reactive oxygen species production in the mitochondria of B65 cells, even at the early stages (3 h) without apparent morphological changes.
Conclusion The 2,5-dimethoxy-substitution of “2C series” induced severe neurotoxicity in both dopaminergic and serotonin-containing neurons. The non-toxic dose of MDMA or METH synergistically enhanced its neurotoxicity in serotonergic neurons. en-copyright= kn-copyright= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FunadaMasahiko en-aut-sei=Funada en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Division of Drug Dependence, National Institute of Mental Health, National Center of Neurology and Psychiatry kn-affil= en-keyword=Psychoactive drugs kn-keyword=Psychoactive drugs en-keyword=2,5-Dimethoxy-substituted phenethylamines kn-keyword=2,5-Dimethoxy-substituted phenethylamines en-keyword=Neurotoxicity kn-keyword=Neurotoxicity en-keyword=Serotonin-containing neurons kn-keyword=Serotonin-containing neurons en-keyword=Dopamine neurons kn-keyword=Dopamine neurons en-keyword=Reactive oxygen species kn-keyword=Reactive oxygen species END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue= article-no= start-page=100347 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Reduction with zinc - Impact on the determination of nitrite and nitrate ions using microfluidic paper-based analytical devices en-subtitle= kn-subtitle= en-abstract= kn-abstract=We used a microfluidic paper-based analytical device (mu PAD) to investigate the influence that zinc reduction exerts on the determination of nitrite and nitrate ions in natural water samples. The mu PAD consists of layered channels for the reduction of nitrate to nitrite with zinc powder and the subsequent detection of nitrite with Griess reagent. The amount of zinc, number of layers, and reaction time for the reduction were optimized to obtain an intense signal for nitrate. Initially, the sensitivity to nitrate corresponded to 55% that of nitrite, which implied an incomplete reduction. We found, however, that zinc decreased the sensitivity to nitrite in both the mu PAD and spectrophotometry. The sensitivity to nitrite was decreased by 48% in spectrophotometry and 68% in the mu PAD following the reaction with zinc. One of the reasons for the decreased sensitivity is attributed to the production of ammonia, as we elucidated that both nitrite and nitrate produced ammonia via the reaction with zinc. The results suggest that the total concentration of nitrite and nitrate must be corrected by constructing a calibration curve for nitrite with zinc, in addition to developing curves for nitrate with zinc and for nitrite without zinc. Using these calibration curves, the absorbance at different concentration ratios of nitrite and nitrate ions could be reproduced via calculation using the calibration curves with zinc for nitrite and nitrate. Eventually, the developed mu PAD was applied to the determination of nitrite and nitrate ions in natural water samples, and the results were compared with those using a conventional spectrophotometric method. The results of the mu PAD are in good agreement with those of conventional spectrophotometry, which suggests that the mu PAD is reliable for the measurement of nitrite and nitrate ions in natural water samples. en-copyright= kn-copyright= en-aut-name=UmedaMika I. en-aut-sei=Umeda en-aut-mei=Mika I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DanchanaKaewta en-aut-sei=Danchana en-aut-mei=Kaewta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiiTakatoshi en-aut-sei=Fujii en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HinoEiichi en-aut-sei=Hino en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DateYusuke en-aut-sei=Date en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AokiKaoru en-aut-sei=Aoki en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KanetaTakashi en-aut-sei=Kaneta en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Okayama University kn-affil= affil-num=3 en-affil=National Institute of Technology, Yonago College kn-affil= affil-num=4 en-affil=National Institute of Technology, Yonago College kn-affil= affil-num=5 en-affil=National Institute of Technology, Yonago College kn-affil= affil-num=6 en-affil=National Institute of Technology, Yonago College kn-affil= affil-num=7 en-affil=Okayama University kn-affil= en-keyword=Microfluidic paper-based analytical device kn-keyword=Microfluidic paper-based analytical device en-keyword=Nitrite ion kn-keyword=Nitrite ion en-keyword=Nitrate ion kn-keyword=Nitrate ion en-keyword=On-site analysis kn-keyword=On-site analysis en-keyword=Environmental analysis kn-keyword=Environmental analysis END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=121 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240731 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pure argyrophilic grain disease revisited: independent effects on limbic, neocortical, and striato-pallido-nigral degeneration and the development of dementia in a series with a low to moderate Braak stage en-subtitle= kn-subtitle= en-abstract= kn-abstract=Agyrophilic grains (AGs) are age-related limbic-predominant lesions in which four-repeat tau is selectively accumulated. Because previous methodologically heterogeneous studies have demonstrated inconsistent findings on the relationship between AGs and dementia, whether AGs affect cognitive function remains unclear. To address this question, we first comprehensively evaluated the distribution and quantity of Gallyas-positive AGs and the severity of neuronal loss in the limbic, neocortical, and subcortical regions in 30 cases of pure argyrophilic grain disease (pAGD) in Braak stages I-IV and without other degenerative diseases, and 34 control cases that had only neurofibrillary tangles with Braak stages I-IV and no or minimal A beta deposits. Then, we examined whether AGs have independent effects on neuronal loss and dementia by employing multivariate ordered logistic regression and binomial logistic regression. Of 30 pAGD cases, three were classified in diffuse form pAGD, which had evident neuronal loss not only in the limbic region but also in the neocortex and subcortical nuclei. In all 30 pAGD cases, neuronal loss developed first in the amygdala, followed by temporo-frontal cortex, hippocampal CA1, substantia nigra, and finally, the striatum and globus pallidus with the progression of Saito AG stage. In multivariate analyses of 30 pAGD and 34 control cases, the Saito AG stage affected neuronal loss in the amygdala, hippocampal CA1, temporo-frontal cortex, striatum, globus pallidus, and substantia nigra independent of the age, Braak stage, and limbic-predominant age-related TDP-43 encephalopathy (LATE-NC) stage. In multivariate analyses of 23 pAGD and 28 control cases that lacked two or more lacunae and/or one or more large infarctions, 100 or more AGs per x 400 visual field in the amygdala (OR 10.02, 95% CI 1.12-89.43) and hippocampal CA1 (OR 12.22, 95% CI 1.70-87.81), and the presence of AGs in the inferior temporal cortex (OR 8.18, 95% CI 1.03-65.13) affected dementia independent of age, moderate Braak stages (III-IV), and LATE-NC. Given these findings, the high density of limbic AGs and the increase of AGs in the inferior temporal gyrus may contribute to the occurrence of dementia through neuronal loss, at least in cases in a low to moderate Braak stage. en-copyright= kn-copyright= en-aut-name=YokotaOsamu en-aut-sei=Yokota en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MikiTomoko en-aut-sei=Miki en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Nakashima-YasudaHanae en-aut-sei=Nakashima-Yasuda en-aut-mei=Hanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshizuHideki en-aut-sei=Ishizu en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiTakashi en-aut-sei=Haraguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkedaChikako en-aut-sei=Ikeda en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HasegawaMasato en-aut-sei=Hasegawa en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyashitaAkinori en-aut-sei=Miyashita en-aut-mei=Akinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IkeuchiTakeshi en-aut-sei=Ikeuchi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishikawaNaoto en-aut-sei=Nishikawa en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakenoshitaShintaro en-aut-sei=Takenoshita en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SudoKoichiro en-aut-sei=Sudo en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TeradaSeishi en-aut-sei=Terada en-aut-mei=Seishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Okayama University Medical School kn-affil= affil-num=4 en-affil=Okayama University Medical School kn-affil= affil-num=5 en-affil=Department of Neurology, National Hospital Organization Minami Okayama Medical Center kn-affil= affil-num=6 en-affil=Okayama University Medical School kn-affil= affil-num=7 en-affil=Dementia Research Project, Tokyo Metropolitan Institute of Medical Science kn-affil= affil-num=8 en-affil=Department of Molecular Genetics, Brain Research Institute, Niigata University kn-affil= affil-num=9 en-affil=Department of Molecular Genetics, Brain Research Institute, Niigata University kn-affil= affil-num=10 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Psychiatry, Tosa Hospital kn-affil= affil-num=13 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Argyrophilic grain kn-keyword=Argyrophilic grain en-keyword=Globus pallidus kn-keyword=Globus pallidus en-keyword=Hippocampal sclerosis kn-keyword=Hippocampal sclerosis en-keyword=Striatum kn-keyword=Striatum en-keyword=Substantia nigra kn-keyword=Substantia nigra en-keyword=Subthalamic nucleus kn-keyword=Subthalamic nucleus END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=15 article-no= start-page=2617 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240723 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Utilizing the Metaverse to Provide Innovative Psychosocial Support for Pediatric, Adolescent, and Young Adult Patients with Rare Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigated the potential of the metaverse in providing psychological support for pediatric and AYA cancer patients, with a focus on those with rare cancers. The research involved ten cancer patients and survivors from four distinct regions in Japan, who participated in metaverse sessions using customizable avatars, facilitating interactions across geographical and temporal barriers. Surveys and qualitative feedback were collected to assess the psychosocial impact of the intervention. The results demonstrated that the metaverse enabled patients to connect with peers, share experiences, and receive emotional support. The anonymity provided by avatars helped reduce appearance-related anxiety and stigma associated with cancer treatment. A case study of a 19-year-old male with spinal Ewing’s sarcoma highlighted the profound emotional relief fostered by metaverse interactions. The findings suggest that integrating virtual spaces into healthcare models can effectively address the unique needs of pediatric and AYA cancer patients, offering a transformative approach to delivering psychosocial support and fostering a global patient community. This innovative intervention has the potential to revolutionize patient care in the digital age. en-copyright= kn-copyright= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshidaHisashi en-aut-sei=Ishida en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatayamaHideki en-aut-sei=Katayama en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaedaNaoko en-aut-sei=Maeda en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaganoAkihito en-aut-sei=Nagano en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OchiMotoharu en-aut-sei=Ochi en-aut-mei=Motoharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkamuraMasako en-aut-sei=Okamura en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwataShintaro en-aut-sei=Iwata en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IkutaKunihiro en-aut-sei=Ikuta en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshidaShinichirou en-aut-sei=Yoshida en-aut-mei=Shinichirou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakaharaRyuichi en-aut-sei=Nakahara en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Medical Information and Assistive Technology Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Palliative and Supportive Care, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, NHO National Hospital Organization Nagoya Medical Center kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Graduate School of Medicine, Gifu University kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Survivorship, Institute for Cancer Control, National Cancer Center kn-affil= affil-num=8 en-affil=Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Graduate School of Medicine, Nagoya University kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery, Graduate School of Medicine, Tohoku University kn-affil= affil-num=11 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=virtual reality kn-keyword=virtual reality en-keyword=metaverse kn-keyword=metaverse en-keyword=adolescent and young adult kn-keyword=adolescent and young adult en-keyword=rare cancer kn-keyword=rare cancer en-keyword=mental health kn-keyword=mental health END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=5536 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240716 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Controlling 229Th isomeric state population in a VUV transparent crystal en-subtitle= kn-subtitle= en-abstract= kn-abstract=The radioisotope thorium-229 (Th-229) is renowned for its extraordinarily low-energy, long-lived nuclear first-excited state. This isomeric state can be excited by vacuum ultraviolet (VUV) lasers and Th-229 has been proposed as a reference transition for ultra-precise nuclear clocks. To assess the feasibility and performance of the nuclear clock concept, time-controlled excitation and depopulation of the Th-229 isomer are imperative. Here we report the population of the Th-229 isomeric state through resonant X-ray pumping and detection of the radiative decay in a VUV transparent Th-229-doped CaF2 crystal. The decay half-life is measured to 447(25) s, with a transition wavelength of 148.18(42) nm and a radiative decay fraction consistent with unity. Furthermore, we report a new "X-ray quenching" effect which allows to de-populate the isomer on demand and effectively reduce the half-life. Such controlled quenching can be used to significantly speed up the interrogation cycle in future nuclear clock schemes. en-copyright= kn-copyright= en-aut-name=HirakiTakahiro en-aut-sei=Hiraki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkaiKoichi en-aut-sei=Okai en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BartokosMichael en-aut-sei=Bartokos en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BeeksKjeld en-aut-sei=Beeks en-aut-mei=Kjeld kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujimotoHiroyuki en-aut-sei=Fujimoto en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukunagaYuta en-aut-sei=Fukunaga en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HabaHiromitsu en-aut-sei=Haba en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KasamatsuYoshitaka en-aut-sei=Kasamatsu en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KitaoShinji en-aut-sei=Kitao en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LeitnerAdrian en-aut-sei=Leitner en-aut-mei=Adrian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MasudaTakahiko en-aut-sei=Masuda en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GuanMing en-aut-sei=Guan en-aut-mei=Ming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NagasawaNobumoto en-aut-sei=Nagasawa en-aut-mei=Nobumoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OgakeRyoichiro en-aut-sei=Ogake en-aut-mei=Ryoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=PimonMartin en-aut-sei=Pimon en-aut-mei=Martin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=PresslerMartin en-aut-sei=Pressler en-aut-mei=Martin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SasaoNoboru en-aut-sei=Sasao en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SchadenFabian en-aut-sei=Schaden en-aut-mei=Fabian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SchummThorsten en-aut-sei=Schumm en-aut-mei=Thorsten kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SetoMakoto en-aut-sei=Seto en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=ShigekawaYudai en-aut-sei=Shigekawa en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ShimizuKotaro en-aut-sei=Shimizu en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SikorskyTomas en-aut-sei=Sikorsky en-aut-mei=Tomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TamasakuKenji en-aut-sei=Tamasaku en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=TakatoriSayuri en-aut-sei=Takatori en-aut-mei=Sayuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=WatanabeTsukasa en-aut-sei=Watanabe en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=YamaguchiAtsushi en-aut-sei=Yamaguchi en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=YodaYoshitaka en-aut-sei=Yoda en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=YoshimiAkihiro en-aut-sei=Yoshimi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=YoshimuraKoji en-aut-sei=Yoshimura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=3 en-affil=Institute for Atomic and Subatomic Physics, TU Wien kn-affil= affil-num=4 en-affil=Institute for Atomic and Subatomic Physics, TU Wien kn-affil= affil-num=5 en-affil=National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=7 en-affil=RIKEN kn-affil= affil-num=8 en-affil=Graduate School of Science, Osaka University kn-affil= affil-num=9 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=10 en-affil=Institute for Atomic and Subatomic Physics, TU Wien kn-affil= affil-num=11 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=12 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=13 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=14 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=15 en-affil=Institute for Atomic and Subatomic Physics, TU Wien kn-affil= affil-num=16 en-affil=Institute for Atomic and Subatomic Physics, TU Wien kn-affil= affil-num=17 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=18 en-affil=Institute for Atomic and Subatomic Physics, TU Wien kn-affil= affil-num=19 en-affil=Institute for Atomic and Subatomic Physics, TU Wien kn-affil= affil-num=20 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=21 en-affil=RIKEN kn-affil= affil-num=22 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=23 en-affil=Institute for Atomic and Subatomic Physics, TU Wien kn-affil= affil-num=24 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=25 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=26 en-affil=National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=27 en-affil=RIKEN kn-affil= affil-num=28 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=29 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=30 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=10 article-no= start-page=1594 end-page=1601 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240713 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Re-administration of platinum-based chemotherapy for recurrent endometrial cancer: an ancillary analysis of the SGSG-012/GOTIC-004/Intergroup study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background We previously demonstrated the applicability of the concept of “platinum sensitivity” in recurrent endometrial cancer. Although immune checkpoint inhibitors have been widely incorporated into endometrial cancer treatment, the debate continues regarding treatment options in patients with recurrent endometrial cancer who have previously received platinum-based chemotherapy. In this study, we assessed the duration of response to secondary platinum-based treatment using pooled data from the SGSG-012/GOTIC-004/Intergroup study.
Methods Among the 279 participants in the SGSG-012/GOTIC-004/Intergroup study wherein platinum-based chemotherapy was re-administered for managing recurrent endometrial cancer between January 2005 and December 2009, 130 (47%) responded to chemotherapy. We compared the relationship between platinum-free interval and duration of secondary platinum-based treatment using pooled data.
Results In 40 patients (31%), the duration of response to secondary platinum-based treatment exceeded the platinum-free interval. The duration of response to secondary platinum-based treatment exceeded 12 months in 51 patients (39%) [platinum-free interval: < 12 months, 14/48 (29%); 12–23 months, 18/43 (42%); 24–35 months, 8/19 (42%); ≥ 36 months, 11/20 (55%)]. In particular, in eight patients (6%), the duration of response to secondary platinum-based treatment exceeded 36 months [platinum-free interval: < 12 months, 3/48 (6%); 12–23 months, 0/19 (0%); 24–35 months, 2/19 (11%); ≥ 36 months, 3/20 (15%)].
Conclusions Re-administration of platinum-based chemotherapy for recurrent endometrial cancer may result in a long-term response exceeding the platinum-free interval in some patients. Even in the current situation, where immune checkpoint inhibitors have been introduced, re-administration of platinum-based chemotherapy is worth considering. en-copyright= kn-copyright= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishioShin en-aut-sei=Nishio en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakeharaKazuhiro en-aut-sei=Takehara en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoShinya en-aut-sei=Sato en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatohToyomi en-aut-sei=Satoh en-aut-mei=Toyomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimadaMuneaki en-aut-sei=Shimada en-aut-mei=Muneaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamaguchiSatoshi en-aut-sei=Yamaguchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanabeHiroshi en-aut-sei=Tanabe en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakanoMasashi en-aut-sei=Takano en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HorieKouji en-aut-sei=Horie en-aut-mei=Kouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakeiYuji en-aut-sei=Takei en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ImaiYuichi en-aut-sei=Imai en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HibinoYumi en-aut-sei=Hibino en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HasegawaKosei en-aut-sei=Hasegawa en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakekumaMunetaka en-aut-sei=Takekuma en-aut-mei=Munetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NakamuraKazuto en-aut-sei=Nakamura en-aut-mei=Kazuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakanoHirokuni en-aut-sei=Takano en-aut-mei=Hirokuni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FujiwaraKeiichi en-aut-sei=Fujiwara en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Kurume University School of Medicine kn-affil= affil-num=3 en-affil=Department of Gynecologic Oncology, NHO Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Tottori University kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Institute of Medicine, University of Tsukuba kn-affil= affil-num=6 en-affil=Department of Gynecology, Tohoku University Hospital kn-affil= affil-num=7 en-affil=Department of Medical Oncology, Hyogo Cancer Center kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Jikei University School of Medicine kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, National Defense Medical College kn-affil= affil-num=10 en-affil=Department of Gynecologic Oncology, Saitama Cancer Center kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Jichi Medical University kn-affil= affil-num=12 en-affil=Department of Obstetrics and Gynecology, Yokohama City University Hospital kn-affil= affil-num=13 en-affil=Department of Gynecologic Oncology, NHO Shikoku Cancer Center kn-affil= affil-num=14 en-affil=Department of Gynecologic Oncology, Saitama Medical University International Medical Center kn-affil= affil-num=15 en-affil=Department of Gynecology, Shizuoka Cancer Center kn-affil= affil-num=16 en-affil=Department of Gynecology, Gunma Prefectural Cancer Center kn-affil= affil-num=17 en-affil=Department of Obstetrics and Gynecology, Jikei University School of Medicine kn-affil= affil-num=18 en-affil=Department of Gynecologic Oncology, Saitama Medical University International Medical Center kn-affil= affil-num=19 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Recurrent endometrial cancer kn-keyword=Recurrent endometrial cancer en-keyword=Re-administration of platinum-based chemotherapy kn-keyword=Re-administration of platinum-based chemotherapy en-keyword=Platinum-free interval kn-keyword=Platinum-free interval en-keyword=Secondary platinum response kn-keyword=Secondary platinum response END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=43 article-no= start-page=eadi8446 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structure of a diatom photosystem II supercomplex containing a member of Lhcx family and dimeric FCPII en-subtitle= kn-subtitle= en-abstract= kn-abstract=Diatoms rely on fucoxanthin chlorophyll a/c-binding proteins (FCPs) for their great success in oceans, which have a great diversity in their pigment, protein compositions, and subunit organizations. We report a unique structure of photosystem II (PSII)-FCPII supercomplex from Thalassiosira pseudonana at 2.68-angstrom resolution by cryo-electron microscopy. FCPIIs within this PSII-FCPII supercomplex exist in dimers and monomers, and a homodimer and a heterodimer were found to bind to a PSII core. The FCPII homodimer is formed by Lhcf7 and associates with PSII through an Lhcx family antenna Lhcx6_1, whereas the heterodimer is formed by Lhcf6 and Lhcf11 and connects to the core together with an Lhcf5 monomer through Lhca2 monomer. An extended pigment network consisting of diatoxanthins, diadinoxanthins, fucoxanthins, and chlorophylls a/c is revealed, which functions in efficient light harvesting, energy transfer, and dissipation. These results provide a structural basis for revealing the energy transfer and dissipation mechanisms and also for the structural diversity of FCP antennas in diatoms. en-copyright= kn-copyright= en-aut-name=FengYue en-aut-sei=Feng en-aut-mei=Yue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiZhenhua en-aut-sei=Li en-aut-mei=Zhenhua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiXiaoyi en-aut-sei=Li en-aut-mei=Xiaoyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShenLili en-aut-sei=Shen en-aut-mei=Lili kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiuXueyang en-aut-sei=Liu en-aut-mei=Xueyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZhouCuicui en-aut-sei=Zhou en-aut-mei=Cuicui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhangJinyang en-aut-sei=Zhang en-aut-mei=Jinyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SangMin en-aut-sei=Sang en-aut-mei=Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HanGuangye en-aut-sei=Han en-aut-mei=Guangye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YangWenqiang en-aut-sei=Yang en-aut-mei=Wenqiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KuangTingyun en-aut-sei=Kuang en-aut-mei=Tingyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WangWenda en-aut-sei=Wang en-aut-mei=Wenda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=2 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=3 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=5 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=6 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=7 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=8 en-affil=China National Botanical Garden kn-affil= affil-num=9 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=10 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=11 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=12 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=13 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue= article-no= start-page=1560 end-page=1571 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240711 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor en-subtitle= kn-subtitle= en-abstract= kn-abstract=An electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines using a proton-exchange membrane (PEM) reactor was developed. Cyanoarenes were then reduced to the corresponding benzylamines at room temperature in the presence of ethyl phosphate. The reduction of nitroarenes proceeded at room temperature, and a variety of anilines were obtained. The quinoline reduction was efficiently promoted by adding a catalytic amount of p-toluenesulfonic acid (PTSA) or pyridinium p-toluenesulfonate (PPTS). Pyridine was also reduced to piperidine in the presence of PTSA. en-copyright= kn-copyright= en-aut-name=MitsudoKoichi en-aut-sei=Mitsudo en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OsakiAtsushi en-aut-sei=Osaki en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoueHaruka en-aut-sei=Inoue en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoEisuke en-aut-sei=Sato en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShidaNaoki en-aut-sei=Shida en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AtobeMahito en-aut-sei=Atobe en-aut-mei=Mahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugaSeiji en-aut-sei=Suga en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Engineering Science and Advanced Chemical Energy Research Center, Yokohama National University kn-affil= affil-num=6 en-affil=Graduate School of Engineering Science and Advanced Chemical Energy Research Center, Yokohama National University kn-affil= affil-num=7 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=cyanoarene kn-keyword=cyanoarene en-keyword=nitroarene kn-keyword=nitroarene en-keyword=PEM reactor kn-keyword=PEM reactor en-keyword=pyridine kn-keyword=pyridine en-keyword=quinoline kn-keyword=quinoline END start-ver=1.4 cd-journal=joma no-vol=208 cd-vols= no-issue= article-no= start-page=145- end-page=154 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240627 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of proportions and prognostic impact of pathological complete response between evaluations of representative specimen and total specimen in primary breast cancer after neoadjuvant chemoradiotherapy: an ancillary study of JCOG0306 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background In JCOG0306 trial, a phase II study to examine the efficacy of neoadjuvant chemotherapy followed by radiation therapy (NAC-RT) to primary breast cancer, pathological complete response (pCR) was evaluated from specimens of the representative cross-section including the tumor center that had been accurately marked [representative specimen (RS) method]. In this ancillary study, we examined if the RS method was comparable to the conventional total specimen (TS) method, which is widely employed in Japan, to identify the pCR group showing excellent prognosis.
Methods We obtained long-term follow-up data of 103 patients enrolled in JCOG0306 trial. As histological therapeutic effect, pCR (ypT0 and ypT0/is) and quasi-pCR [QpCR, ypT0/is plus Grade 2b (only a few remaining invasive cancer cells)] were evaluated with RS and TS methods. Concordance of pCR between these two methods and associations of the pCR with prognosis were examined.
Results ypT0, ypT0/is, and QpCR were observed in 28 (27.2%), 39 (37.9%), and 45 (43.7%) patients with RS method, whereas these were 20 (19.4%), 25 (24.3%) and 40 (38.9%) with TS method, respectively. Between RS and TS methods, concordance proportions of ypT0 and ypTis were 92.2% and 86.4%, respectively. Risk of recurrence of ypT0/is group was lower than that of non-ypT0/is group (HR 0.408, 95% CI [0.175–0.946], P = 0.037) and risk of death of ypT0/is group was lower than that of non-ypT0/is group (HR 0.251, 95% CI [0.073–0.857], P = 0.027). The ypT0 and ypT0/is groups with RS method showed excellent prognosis similarly with those with TS method, and RS method was able to differentiate the OS and RFS between pCR and non-pCR than TS method significantly even if pCR was classified ypT0 or ypT0/is. With TS method, QpCR criteria stratified patients into the better and worse prognosis groupsmore clearly than pCR criteria of ypT0 or ypT0/is.
Conclusions RS method was comparable to TS method for the evaluation of pCR in the patients who received NAC-RT to primary breast cancer provided the tumor center was accurately marked. As pCR criteria with RS method, ypT0/is appeared more appropriate than ypT0. en-copyright= kn-copyright= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsudaHitoshi en-aut-sei=Tsuda en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SasakiKeita en-aut-sei=Sasaki en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MizusawaJunki en-aut-sei=Mizusawa en-aut-mei=Junki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkiyamaFutoshi en-aut-sei=Akiyama en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurosumiMasafumi en-aut-sei=Kurosumi en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SawakiMasataka en-aut-sei=Sawaki en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TamuraNobuko en-aut-sei=Tamura en-aut-mei=Nobuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaKiyo en-aut-sei=Tanaka en-aut-mei=Kiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KogawaTakahiro en-aut-sei=Kogawa en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakahashiMina en-aut-sei=Takahashi en-aut-mei=Mina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HayashiNaoki en-aut-sei=Hayashi en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MukaiHirofumi en-aut-sei=Mukai en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MasudaNorikazu en-aut-sei=Masuda en-aut-mei=Norikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IwataHiroji en-aut-sei=Iwata en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Basic Pathology, National Defense Medical College kn-affil= affil-num=3 en-affil=JCOG Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=4 en-affil=JCOG Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Pathology, Cancer Institute Hospital kn-affil= affil-num=6 en-affil=Department of Diagnostic Pathology, Kameda Kyobashi Clinic kn-affil= affil-num=7 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Breast Surgery, Toranomon Hospital kn-affil= affil-num=9 en-affil=Department of Breast Surgery, Toranomon Hospital kn-affil= affil-num=10 en-affil=Department of Breast Medical Oncology, Cancer Institute Hospital kn-affil= affil-num=11 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=12 en-affil=Department of Breast Surgery Oncology, St Lukes International Hospital kn-affil= affil-num=13 en-affil=Department of Breast and Medical Oncology, National Cancer Center Hospital East kn-affil= affil-num=14 en-affil=Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital kn-affil= affil-num=15 en-affil=Department of Breast Medical Oncology, Cancer Institute Hospital kn-affil= affil-num=16 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Neoadjuvant chemoradiotherapy kn-keyword=Neoadjuvant chemoradiotherapy en-keyword=Pathological therapeutic effect kn-keyword=Pathological therapeutic effect en-keyword=Specimen sampling method kn-keyword=Specimen sampling method END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=2926 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240408 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Large-volume focus control at 10 MHz refresh rate via fast line-scanning amplitude-encoded scattering-assisted holography en-subtitle= kn-subtitle= en-abstract= kn-abstract=The capability of focus control has been central to optical technologies that require both high temporal and spatial resolutions. However, existing varifocal lens schemes are commonly limited to the response time on the microsecond timescale and share the fundamental trade-off between the response time and the tuning power. Here, we propose an ultrafast holographic focusing method enabled by translating the speed of a fast 1D beam scanner into the speed of the complex wavefront modulation of a relatively slow 2D spatial light modulator. Using a pair of a digital micromirror device and a resonant scanner, we demonstrate an unprecedented refresh rate of focus control of 31 MHz, which is more than 1,000 times faster than the switching rate of a digital micromirror device. We also show that multiple micrometer-sized focal spots can be independently addressed in a range of over 1 MHz within a large volume of 5 mm × 5 mm × 5.5 mm, validating the superior spatiotemporal characteristics of the proposed technique – high temporal and spatial precision, high tuning power, and random accessibility in a three-dimensional space. The demonstrated scheme offers a new route towards three-dimensional light manipulation in the 100 MHz regime. en-copyright= kn-copyright= en-aut-name=ShibukawaAtsushi en-aut-sei=Shibukawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiguchiRyota en-aut-sei=Higuchi en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SongGookho en-aut-sei=Song en-aut-mei=Gookho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MikamiHideharu en-aut-sei=Mikami en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SudoYuki en-aut-sei=Sudo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JangMooseok en-aut-sei=Jang en-aut-mei=Mooseok kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Research Institute for Electronic Science, Hokkaido University kn-affil= affil-num=2 en-affil=Research Institute for Electronic Science, Hokkaido University kn-affil= affil-num=3 en-affil=Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology kn-affil= affil-num=4 en-affil=Research Institute for Electronic Science, Hokkaido University kn-affil= affil-num=5 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology kn-affil= END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=3 article-no= start-page=281 end-page=289 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240408 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Volume X-Ray Micro-Computed Tomography Analysis of the Early Cephalized Central Nervous System in a Marine Flatworm, Stylochoplana pusilla en-subtitle= kn-subtitle= en-abstract= kn-abstract=Platyhelminthes are a phylum of simple bilaterian invertebrates with prototypic body systems. Compared with non-bilaterians such as cnidarians, the bilaterians are likely to exhibit integrated free-moving behaviors, which require a concentrated nervous system “brain” rather than the distributed nervous system of radiatans. Marine flatworms have an early cephalized ‘central’ nervous system compared not only with non-bilaterians but also with parasitic flatworms or freshwater planarians. In this study, we used the marine flatworm Stylochoplana pusilla as an excellent model organism in Platyhelminthes because of the early cephalized central nervous system. Here, we investigated the three-dimensional structures of the flatworm central nervous system by the use of X-ray micro-computed tomography (micro-CT) in a synchrotron radiation facility. We found that the obtained tomographic images were sufficient to discriminate some characteristic structures of the nervous system, including nerve cords around the cephalic ganglion, mushroom body-like structures, and putative optic nerves forming an optic commissure-like structure. Through the micro-CT imaging, we could obtain undistorted serial section images, permitting us to visualize precise spatial relationships of neuronal subpopulations and nerve tracts. 3-D micro-CT is very effective in the volume analysis of the nervous system at the cellular level; the methodology is straightforward and could be applied to many other non-model organisms. en-copyright= kn-copyright= en-aut-name=IkenagaTakanori en-aut-sei=Ikenaga en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiAoshi en-aut-sei=Kobayashi en-aut-mei=Aoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakeuchiAkihisa en-aut-sei=Takeuchi en-aut-mei=Akihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UesugiKentaro en-aut-sei=Uesugi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaezawaTakanobu en-aut-sei=Maezawa en-aut-mei=Takanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShibataNorito en-aut-sei=Shibata en-aut-mei=Norito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakamotoTatsuya en-aut-sei=Sakamoto en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SakamotoHirotaka en-aut-sei=Sakamoto en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Science and Engineering, Kagoshima University kn-affil= affil-num=2 en-affil=Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Japan Synchrotron Radiation Research Institute/SPring-8 kn-affil= affil-num=4 en-affil=Japan Synchrotron Radiation Research Institute/SPring-8 kn-affil= affil-num=5 en-affil=Department of Integrated Science and Technology, National Institute of Technology, Tsuyama College kn-affil= affil-num=6 en-affil=Department of Integrated Science and Technology, National Institute of Technology, Tsuyama College kn-affil= affil-num=7 en-affil=Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=bilaterians kn-keyword=bilaterians en-keyword=micro-CT scan kn-keyword=micro-CT scan en-keyword=central nervous system kn-keyword=central nervous system en-keyword=Platyhelminthes kn-keyword=Platyhelminthes en-keyword=marine flatworms kn-keyword=marine flatworms END start-ver=1.4 cd-journal=joma no-vol=121 cd-vols= no-issue=25 article-no= start-page=e2322765121 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Argonaute-independent, Dicer-dependent antiviral defense against RNA viruses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Antiviral RNA interference (RNAi) is conserved from yeasts to mammals. Dicer recognizes and cleaves virus-derived double-stranded RNA (dsRNA) and/or structured single-stranded RNA (ssRNA) into small-interfering RNAs, which guide effector Argonaute to homologous viral RNAs for digestion and inhibit virus replication. Thus, Argonaute is believed to be essential for antiviral RNAi. Here, we show Argonaute-independent, Dicer-dependent antiviral defense against dsRNA viruses using Cryphonectria parasitica (chestnut blight fungus), which is a model filamentous ascomycetous fungus and hosts a variety of viruses. The fungus has two dicer-like genes (dcl1 and dcl2) and four argonaute-like genes (agl1 to agl4). We prepared a suite of single to quadruple agl knockout mutants with or without dcl disruption. We tested these mutants for antiviral activities against diverse dsRNA viruses and ssRNA viruses. Although both DCL2 and AGL2 worked as antiviral players against some RNA viruses, DCL2 without argonaute was sufficient to block the replication of other RNA viruses. Overall, these results indicate the existence of a Dicer-alone defense and different degrees of susceptibility to it among RNA viruses. We discuss what determines the great difference in susceptibility to the Dicer-only defense. en-copyright= kn-copyright= en-aut-name=SatoYukiyo en-aut-sei=Sato en-aut-mei=Yukiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=RNAi kn-keyword=RNAi en-keyword=Argonaute kn-keyword=Argonaute en-keyword=Dicer kn-keyword=Dicer en-keyword=fungal virus kn-keyword=fungal virus en-keyword=chestnut blight kn-keyword=chestnut blight END start-ver=1.4 cd-journal=joma no-vol=121 cd-vols= no-issue=25 article-no= start-page=e2318150121 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Replication of single viruses across the kingdoms, Fungi, Plantae, and Animalia en-subtitle= kn-subtitle= en-abstract= kn-abstract=It is extremely rare that a single virus crosses host barriers across multiple kingdoms. Based on phylogenetic and paleovirological analyses, it has previously been hypothesized that single members of the family Partitiviridae could cross multiple kingdoms. Partitiviridae accommodates members characterized by their simple bisegmented double-stranded RNA genome; asymptomatic infections of host organisms; the absence of an extracellular route for entry in nature; and collectively broad host range. Herein, we show the replicability of single fungal partitiviruses in three kingdoms of host organisms: Fungi, Plantae, and Animalia. Betapartitiviruses of the phytopathogenic fungusRosellinia necatrix could replicate in protoplasts of the carrot (Daucus carota), Nicotiana benthamiana and Nicotiana tabacum, in some cases reaching a level detectable by agarose gel electrophoresis. Moreover, betapartitiviruses showed more robust replication than the tested alphapartitiviruses. One of the fungal betapartitiviruses, RnPV18, could persistently and stably infect carrot plants regenerated from virion-transfected protoplasts. Both alpha- and betapartitiviruses, although with different host preference, could replicate in two insect cell lines derived from the fall armyworm Spodoptera frugiperda and the fruit fly Drosophila melanogaster. Our results indicate the replicability of single partitiviruses in members of three kingdoms and provide insights into virus adaptation, host jumping, and evolution. en-copyright= kn-copyright= en-aut-name=TelengechPaul en-aut-sei=Telengech en-aut-mei=Paul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HyodoKiwamu en-aut-sei=Hyodo en-aut-mei=Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IchikawaHiroaki en-aut-sei=Ichikawa en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuwataRyusei en-aut-sei=Kuwata en-aut-mei=Ryusei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Agrobiological Sciences, National Agriculture and Food Research Organization kn-affil= affil-num=4 en-affil=Faculty of Veterinary Medicine, Okayama University of Science kn-affil= affil-num=5 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=cross- kingdom infection kn-keyword=cross- kingdom infection en-keyword=partitivirus kn-keyword=partitivirus en-keyword=fungal virus kn-keyword=fungal virus en-keyword=Plantae kn-keyword=Plantae en-keyword=Animalia kn-keyword=Animalia END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=12 article-no= start-page=e7351 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240625 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prevalence of neurotrophic tropomyosin receptor kinase (NTRK) fusion gene positivity in patients with solid tumors in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Members of the neurotrophic tropomyosin receptor kinase (NTRK) gene family, NTRK1, NTRK2, and NTRK3 encode TRK receptor tyrosine kinases. Intra- or inter-chromosomal gene rearrangements produce NTRK gene fusions encoding fusion proteins which are oncogenic drivers in various solid tumors.
Methods: This study investigated the prevalence of NTRK fusion genes and identified fusion partners in Japanese patients with solid tumors recorded in the Center for Cancer Genomics and Advanced Therapeutics database of comprehensive genomic profiling test.
Results: In the analysis population (n = 46,621), NTRK fusion genes were detected in 91 patients (0.20%). The rate was higher in pediatric cases (<18 years; 1.69%) than in adults (0.16%). NTRK gene fusions were identified in 21 different solid tumor types involving 38 different partner genes including 22 (57.9%) previously unreported NTRK gene fusions. The highest frequency of NTRK gene fusions was head and neck cancer (1.31%) and thyroid cancer (1.31%), followed by soft tissue sarcoma (STS; 0.91%). A total of 97 NTRK fusion gene partners were analyzed involving mainly NTRK1 (49.5%) or NTRK3 (44.2%) gene fusions. The only fusion gene detected in head and neck cancer was ETV6::NTRK3 (n = 22); in STS, ETV6::NTRK3 (n = 7) and LMNA::NTRK1 (n = 5) were common. Statistically significant mutual exclusivity of NTRK fusions with alterations was confirmed in TP53, KRAS, and APC. NTRK gene fusion was detected from 11 STS cases: seven unclassified sarcoma, three sarcoma NOS, and one Ewing sarcoma.
Conclusions: NTRK gene fusion identification in solid tumors enables accurate diagnosis and potential TRK inhibitor therapy. en-copyright= kn-copyright= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OsoneTatsunori en-aut-sei=Osone en-aut-mei=Tatsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OgawaToru en-aut-sei=Ogawa en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaguchiTomoyuki en-aut-sei=Taguchi en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HattoriKana en-aut-sei=Hattori en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KohsakaShinji en-aut-sei=Kohsaka en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Medical Affairs & Pharmacovigilance, Bayer Yakuhin, Ltd kn-affil= affil-num=4 en-affil=Medical Affairs & Pharmacovigilance, Bayer Yakuhin, Ltd kn-affil= affil-num=5 en-affil=Medical Affairs & Pharmacovigilance, Bayer Yakuhin, Ltd kn-affil= affil-num=6 en-affil=National Cancer Center Research Institute kn-affil= en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=neurotrophic tropomyosin receptor kinase (NTRK) gene fusion kn-keyword=neurotrophic tropomyosin receptor kinase (NTRK) gene fusion en-keyword=next-generation sequencing kn-keyword=next-generation sequencing en-keyword=solid tumors kn-keyword=solid tumors END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue= article-no= start-page=1371307 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240528 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dissection of the signal transduction machinery responsible for the lysyl oxidase-like 4-mediated increase in invasive motility in triple-negative breast cancer cells: mechanistic insight into the integrin-β1-NF-κB-MMP9 axis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Triple-negative breast cancer (TNBC) cells are a highly formidable cancer to treat. Nonetheless, by continued investigation into the molecular biology underlying the complex regulation of TNBC cell activity, vulnerabilities can be exposed as potential therapeutic targets at the molecular level. We previously revealed that lysyl oxidase-like 4 (LOXL4) promotes the invasiveness of TNBC cells via cell surface annexin A2 as a novel binding substrate of LOXL4, which promotes the abundant localization of integrin-beta 1 at the cancer plasma membrane. However, it has yet to be uncovered how the LOXL4-mediated abundance of integrin-beta 1 hastens the invasive outgrowth of TNBC cells at the molecular level.
Methods LOXL4-overexpressing stable clones were established from MDA-MB-231 cells and subjected to molecular analyses, real-time qPCR and zymography to clarify their invasiveness, signal transduction, and matrix metalloprotease (MMP) activity, respectively.
Results Our results show that LOXL4 potently promotes the induction of matrix metalloprotease 9 (MMP9) via activation of nuclear factor-kappa B (NF-kappa B). Our molecular analysis revealed that TNF receptor-associated factor 4 (TRAF4) and TGF-beta activated kinase 1 (TAK1) were required for the activation of NF-kappa B through I kappa beta kinase kinase (IKK alpha/beta) phosphorylation.
Conclusion Our results demonstrate that the newly identified LOXL4-mediated axis, integrin-beta 1-TRAF4-TAK1-IKK alpha/beta-I kappa beta alpha-NF-kappa B-MMP9, is crucial for TNBC cell invasiveness. en-copyright= kn-copyright= en-aut-name=JiangFan en-aut-sei=Jiang en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChenYouyi en-aut-sei=Chen en-aut-mei=Youyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KomalasariNi Luh Gede Yoni en-aut-sei=Komalasari en-aut-mei=Ni Luh Gede Yoni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Kasano-CamonesCarlos Ichiro en-aut-sei=Kasano-Camones en-aut-mei=Carlos Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NinomiyaKazumi en-aut-sei=Ninomiya en-aut-mei=Kazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MurataHitoshi en-aut-sei=Murata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoKen-Ichi en-aut-sei=Yamamoto en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GoharaYuma en-aut-sei=Gohara en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OchiToshiki en-aut-sei=Ochi en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=RumaI. Made Winarsa en-aut-sei=Ruma en-aut-mei=I. Made Winarsa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SumardikaI. Wayan en-aut-sei=Sumardika en-aut-mei=I. Wayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ZhouJin en-aut-sei=Zhou en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HonjoTomoko en-aut-sei=Honjo en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SakaguchiYoshihiko en-aut-sei=Sakaguchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamauchiAkira en-aut-sei=Yamauchi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KuribayashiFutoshi en-aut-sei=Kuribayashi en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FutamiJunichiro en-aut-sei=Futami en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KondoEisaku en-aut-sei=Kondo en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=InoueYusuke en-aut-sei=Inoue en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=6 en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= affil-num=7 en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= affil-num=8 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=13 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=14 en-affil=Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology kn-affil= affil-num=15 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=16 en-affil=Department of Microbiology, Tokushima Bunri University kn-affil= affil-num=17 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=18 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=19 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=20 en-affil=Division of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical University kn-affil= affil-num=21 en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= affil-num=22 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=invasion kn-keyword=invasion en-keyword=lysyl oxidase kn-keyword=lysyl oxidase en-keyword=NF-κB kn-keyword=NF-κB en-keyword=MMP9 kn-keyword=MMP9 END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=4610 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An NLR paralog Pit2 generated from tandem duplication of Pit1 fine-tunes Pit1 localization and function en-subtitle= kn-subtitle= en-abstract= kn-abstract=NLR family proteins act as intracellular receptors. Gene duplication amplifies the number of NLR genes, and subsequent mutations occasionally provide modifications to the second gene that benefits immunity. However, evolutionary processes after gene duplication and functional relationships between duplicated NLRs remain largely unclear. Here, we report that the rice NLR protein Pit1 is associated with its paralogue Pit2. The two are required for the resistance to rice blast fungus but have different functions: Pit1 induces cell death, while Pit2 competitively suppresses Pit1-mediated cell death. During evolution, the suppression of Pit1 by Pit2 was probably generated through positive selection on two fate-determining residues in the NB-ARC domain of Pit2, which account for functional differences between Pit1 and Pit2. Consequently, Pit2 lost its plasma membrane localization but acquired a new function to interfere with Pit1 in the cytosol. These findings illuminate the evolutionary trajectory of tandemly duplicated NLR genes after gene duplication. en-copyright= kn-copyright= en-aut-name=LiYuying en-aut-sei=Li en-aut-mei=Yuying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangQiong en-aut-sei=Wang en-aut-mei=Qiong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JiaHuimin en-aut-sei=Jia en-aut-mei=Huimin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshikawaKazuya en-aut-sei=Ishikawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KosamiKen-Ichi en-aut-sei=Kosami en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UebaTakahiro en-aut-sei=Ueba en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujimotoAtsumi en-aut-sei=Tsujimoto en-aut-mei=Atsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamanakaMiki en-aut-sei=Yamanaka en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YabumotoYasuyuki en-aut-sei=Yabumoto en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MikiDaisuke en-aut-sei=Miki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SasakiEriko en-aut-sei=Sasaki en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FukaoYoichiro en-aut-sei=Fukao en-aut-mei=Yoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraMasayuki en-aut-sei=Fujiwara en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Kaneko-KawanoTakako en-aut-sei=Kaneko-Kawano en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanLi en-aut-sei=Tan en-aut-mei=Li kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KojimaChojiro en-aut-sei=Kojima en-aut-mei=Chojiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WingRod A. en-aut-sei=Wing en-aut-mei=Rod A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SebastianAlfino en-aut-sei=Sebastian en-aut-mei=Alfino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=NishimuraHideki en-aut-sei=Nishimura en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FukadaFumi en-aut-sei=Fukada en-aut-mei=Fumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NiuQingfeng en-aut-sei=Niu en-aut-mei=Qingfeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ShimizuMotoki en-aut-sei=Shimizu en-aut-mei=Motoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YoshidaKentaro en-aut-sei=Yoshida en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TerauchiRyohei en-aut-sei=Terauchi en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ShimamotoKo en-aut-sei=Shimamoto en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KawanoYoji en-aut-sei=Kawano en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences kn-affil= affil-num=2 en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=3 en-affil=College of Agronomy, Jiangxi Agricultural University kn-affil= affil-num=4 en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=5 en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=6 en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology kn-affil= affil-num=7 en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology kn-affil= affil-num=8 en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology kn-affil= affil-num=9 en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology kn-affil= affil-num=10 en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=11 en-affil=Faculty of Science, Kyushu University kn-affil= affil-num=12 en-affil=Department of Bioinformatics, Ritsumeikan University kn-affil= affil-num=13 en-affil=YANMAR HOLDINGS Co., Ltd. kn-affil= affil-num=14 en-affil=College of Pharmaceutical Sciences, Ritsumeikan University kn-affil= affil-num=15 en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=16 en-affil=Graduate School of Engineering Science, Yokohama National University kn-affil= affil-num=17 en-affil=Arizona Genomics Institute, School of Plant Sciences, University of Arizona kn-affil= affil-num=18 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=19 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=20 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=21 en-affil=Advanced Academy, Anhui Agricultural University, Research Centre for Biological Breeding Technology kn-affil= affil-num=22 en-affil=Iwate Biotechnology Research Center kn-affil= affil-num=23 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=24 en-affil=Iwate Biotechnology Research Center kn-affil= affil-num=25 en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology kn-affil= affil-num=26 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=3 article-no= start-page=e004237 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202405 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not.
Research design and methods Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year.
Results The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR.
Conclusions Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.Trial registration number UMIN000011525. en-copyright= kn-copyright= en-aut-name=UenoAsami en-aut-sei=Ueno en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiseKoki en-aut-sei=Mise en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamaguchiSatoshi en-aut-sei=Yamaguchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KannoAyaka en-aut-sei=Kanno en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NojimaIchiro en-aut-sei=Nojima en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiguchiChigusa en-aut-sei=Higuchi en-aut-mei=Chigusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShikataKenichi en-aut-sei=Shikata en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyamotoSatoshi en-aut-sei=Miyamoto en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakatsukaAtsuko en-aut-sei=Nakatsuka en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=EguchiJun en-aut-sei=Eguchi en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HidaKazuyuki en-aut-sei=Hida en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatayamaAkihiro en-aut-sei=Katayama en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=WatanabeMayu en-aut-sei=Watanabe en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NakatoTatsuaki en-aut-sei=Nakato en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ToneAtsuhito en-aut-sei=Tone en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TeshigawaraSanae en-aut-sei=Teshigawara en-aut-mei=Sanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MatsuokaTakashi en-aut-sei=Matsuoka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KameiShinji en-aut-sei=Kamei en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MurakamiKazutoshi en-aut-sei=Murakami en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ShimizuIkki en-aut-sei=Shimizu en-aut-mei=Ikki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MiyashitaKatsuhito en-aut-sei=Miyashita en-aut-mei=Katsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=AndoShinichiro en-aut-sei=Ando en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NunoueTomokazu en-aut-sei=Nunoue en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center kn-affil= affil-num=14 en-affil=Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center kn-affil= affil-num=15 en-affil=Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center kn-affil= affil-num=16 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=17 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=18 en-affil=Okayama Saiseikai General Hospital kn-affil= affil-num=19 en-affil=Department of Diabetic Medicine, Kurashiki Central Hospital kn-affil= affil-num=20 en-affil=Department of Diabetic Medicine, Kurashiki Central Hospital kn-affil= affil-num=21 en-affil=Department of Diabetic Medicine, Kurashiki Central Hospital kn-affil= affil-num=22 en-affil=Sakakibara Heart Institute of Okayama kn-affil= affil-num=23 en-affil=Japanese Red Cross Okayama Hospital kn-affil= affil-num=24 en-affil=Okayama City General Medical Center kn-affil= affil-num=25 en-affil=Nunoue Clinic kn-affil= affil-num=26 en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=4535 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240528 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structure and distinct supramolecular organization of a PSII-ACPII dimer from a cryptophyte alga Chroomonas placoidea en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cryptophyte algae are an evolutionarily distinct and ecologically important group of photosynthetic unicellular eukaryotes. Photosystem II (PSII) of cryptophyte algae associates with alloxanthin chlorophyll a/c-binding proteins (ACPs) to act as the peripheral light-harvesting system, whose supramolecular organization is unknown. Here, we purify the PSII-ACPII supercomplex from a cryptophyte alga Chroomonas placoidea (C. placoidea), and analyze its structure at a resolution of 2.47 & Aring; using cryo-electron microscopy. This structure reveals a dimeric organization of PSII-ACPII containing two PSII core monomers flanked by six symmetrically arranged ACPII subunits. The PSII core is conserved whereas the organization of ACPII subunits exhibits a distinct pattern, different from those observed so far in PSII of other algae and higher plants. Furthermore, we find a Chl a-binding antenna subunit, CCPII-S, which mediates interaction of ACPII with the PSII core. These results provide a structural basis for the assembly of antennas within the supercomplex and possible excitation energy transfer pathways in cryptophyte algal PSII, shedding light on the diversity of supramolecular organization of photosynthetic machinery. en-copyright= kn-copyright= en-aut-name=MaoZhiyuan en-aut-sei=Mao en-aut-mei=Zhiyuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiXingyue en-aut-sei=Li en-aut-mei=Xingyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiZhenhua en-aut-sei=Li en-aut-mei=Zhenhua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShenLiangliang en-aut-sei=Shen en-aut-mei=Liangliang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiXiaoyi en-aut-sei=Li en-aut-mei=Xiaoyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YangYanyan en-aut-sei=Yang en-aut-mei=Yanyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WangWenda en-aut-sei=Wang en-aut-mei=Wenda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KuangTingyun en-aut-sei=Kuang en-aut-mei=Tingyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HanGuangye en-aut-sei=Han en-aut-mei=Guangye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=2 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=3 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=5 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=6 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=7 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=8 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=9 en-affil=Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=13 end-page=18 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240526 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Application of a Deep Reinforcement Learning Algorithm to Virtual Machine Migration Control in Multi-Stage Information Processing Systems en-subtitle= kn-subtitle= en-abstract= kn-abstract=This paper tackles a Virtual Machine (VM) migration control problem to maximize the progress (accuracy) of information processing tasks in multi-stage information processing systems. The conventional methods for this problem (e.g., VM sweeping method and VM number averaging method) are effective only for specific situations, such as when the system load is high. In this paper, in order to achieve high accuracy in various situations, we propose a VM migration method using a Deep Reinforcement Learning (DRL) algorithm. It is difficult to directly apply a DRL algorithm to the VM migration control problem because the size of the solution space of the problem dynamically changes according to the number of VMs staying in the system while the size of the agent’s action space is fixed in DRL algorithms. Therefore, the proposed method divides the VM migration control problem into two problems: the problem of determining only the VM distribution (i.e., the proportion of the number of VMs deployed on each edge server) and the problem of determining the locations of all the VMs so that it follows the determined VM distribution. The former problem is solved by a DRL algorithm, and the latter problem is solved by a heuristic method. The simulation results confirm that our proposed method can select quasi-optimal VM locations in various situations with different link delays. en-copyright= kn-copyright= en-aut-name=FukushimaYukinobu en-aut-sei=Fukushima en-aut-mei=Yukinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KoujitaniYuki en-aut-sei=Koujitani en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakaneKazutoshi en-aut-sei=Nakane en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TarutaniYuta en-aut-sei=Tarutani en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WuCelimuge en-aut-sei=Wu en-aut-mei=Celimuge kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JiYusheng en-aut-sei=Ji en-aut-mei=Yusheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YokohiraTokumi en-aut-sei=Yokohira en-aut-mei=Tokumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MuraseTutomu en-aut-sei=Murase en-aut-mei=Tutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Okayama University kn-affil= affil-num=3 en-affil=Nagoya University kn-affil= affil-num=4 en-affil=Okayama University kn-affil= affil-num=5 en-affil=The Univ. of Electro-Commun. kn-affil= affil-num=6 en-affil=National Institute of Informatics kn-affil= affil-num=7 en-affil=Okayama University kn-affil= affil-num=8 en-affil=Nagoya University kn-affil= en-keyword=Multi-stage information processing system kn-keyword=Multi-stage information processing system en-keyword=VM migration control kn-keyword=VM migration control en-keyword=Deep reinforcement learning kn-keyword=Deep reinforcement learning en-keyword=Deep Deterministic Policy Gradient (DDPG) kn-keyword=Deep Deterministic Policy Gradient (DDPG) END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=19 article-no= start-page=21287 end-page=21297 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Superstructure of Fe5–xGeTe2 Determined by Te K-Edge Extended X-ray Absorption Fine Structure and Te Kα X-ray Fluorescence Holography en-subtitle= kn-subtitle= en-abstract= kn-abstract=The local structure of the two-dimensional van der Waals material, Fe5–xGeTe2, which exhibits unique structural/magnetic phase transitions, was investigated by Te K-edge extended X-ray absorption fine structure (EXAFS) and Te Kα X-ray fluorescence holography (XFH) over a wide temperature range. The formation of a trimer of Te atoms at low temperatures has been fully explored using these methods. An increase in the Te–Fe distance at approximately 150 K was suggested by EXAFS and presumably indicates the formation of a Te trimer. Moreover, XFH displayed clear atomic images of Te atoms. Additionally, the distance between the Te atoms shortened, as confirmed from the atomic images reconstructed from XFH, indicating the formation of a trimer of Te atoms, i.e., a charge-ordered (3⎯⎯√×3⎯⎯√)𝑅30◦ superstructure. Furthermore, Te Kα XFH provided unambiguous atomic images of Fe atoms occupying the Fe1 site; the images were not clearly observed in the Ge Kα XFH that was previously reported because of the low occupancy of Fe and Ge atoms. In this study, EXAFS and XFH clearly showed the local structure around the Te atom; in particular, the formation of Te trimers caused by charge-ordered phase transitions was clearly confirmed. The charge-ordered phase transition is fully discussed based on the structural variation at low temperatures, as established from EXAFS and XFH. en-copyright= kn-copyright= en-aut-name=EguchiRitsuko en-aut-sei=Eguchi en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SekharHalubai en-aut-sei=Sekhar en-aut-mei=Halubai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraKoji en-aut-sei=Kimura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MasaiHirokazu en-aut-sei=Masai en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HappoNaohisa en-aut-sei=Happo en-aut-mei=Naohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkedaMitsuki en-aut-sei=Ikeda en-aut-mei=Mitsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoYuki en-aut-sei=Yamamoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UtsumiMasaki en-aut-sei=Utsumi en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=GotoHidenori en-aut-sei=Goto en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakabayashiYasuhiro en-aut-sei=Takabayashi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TajiriHiroo en-aut-sei=Tajiri en-aut-mei=Hiroo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HayashiKoichi en-aut-sei=Hayashi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KubozonoYoshihiro en-aut-sei=Kubozono en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Physical Science and Technology, Nagoya Institute of Technology kn-affil= affil-num=3 en-affil=Department of Physical Science and Technology, Nagoya Institute of Technology kn-affil= affil-num=4 en-affil=Department of Materials and Chemistry, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=5 en-affil=Graduate School of Information Sciences, Hiroshima City University kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=7 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=8 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=9 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=10 en-affil=Department of Physical Science and Technology, Nagoya Institute of Technology kn-affil= affil-num=11 en-affil=Japan Synchrotron Radiation Research Institute (JASRI) kn-affil= affil-num=12 en-affil=Department of Physical Science and Technology, Nagoya Institute of Technology kn-affil= affil-num=13 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=127 cd-vols= no-issue=25 article-no= start-page=12295 end-page=12303 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230620 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Li-Ion Transport and Solution Structure in Sulfolane-Based Localized High-Concentration Electrolytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Localized high-concentration electrolytes (LHCEs), which are mixtures of highly concentrated electrolytes (HCEs) and non-coordinating diluents, have attracted significant interest as promising liquid electrolytes for next-generation Li secondary batteries, owing to their various beneficial properties both in the bulk and at the electrode/electrolyte interface. We previously reported that the large Li+-ion transference number in sulfolane (SL)-based HCEs, attributed to the unique exchange/hopping-like Li+-ion conduction, decreased upon dilution with the non-coordinating hydrofluoroether (HFE) despite the retention of the local Li+-ion coordination structure. Therefore, in this study, we investigated the effects of HFE dilution on the Li+ transference number and the solution structure of SL-based LHCEs via the analysis of dynamic ion correlations and molecular dynamics simulations. The addition of HFE caused nano-segregation in the SL-based LHCEs to afford polar and nonpolar domains and fragmentation of the polar ion-conducting pathway into smaller clusters with increasing HFE content. Analysis of the dynamic ion correlations revealed that the anti-correlated Li+–Li+ motions were more pronounced upon HFE addition, suggesting that the Li+ exchange/hopping conduction is obstructed by the non-ion-conducting HFE-rich domains. Thus, the HFE addition affects the entire solution structure and ion transport without significantly affecting the local Li+-ion coordination structure. Further studies on ion transport in LHCEs would help obtain a design principle for liquid electrolytes with high ionic conductivity and large Li+-ion transference numbers. en-copyright= kn-copyright= en-aut-name=SudohTaku en-aut-sei=Sudoh en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaShuhei en-aut-sei=Ikeda en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShigenobuKeisuke en-aut-sei=Shigenobu en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuzukiSeiji en-aut-sei=Tsuzuki en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DokkoKaoru en-aut-sei=Dokko en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WatanabeMasayoshi en-aut-sei=Watanabe en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShinodaWataru en-aut-sei=Shinoda en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UenoKazuhide en-aut-sei=Ueno en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Taku Sudoh Department of Chemistry and Life Science, Yokohama National University kn-affil= affil-num=2 en-affil=Department of Materials Chemistry, Nagoya University kn-affil= affil-num=3 en-affil=Department of Chemistry and Life Science, Yokohama National University kn-affil= affil-num=4 en-affil=Advanced Chemical Energy Research Centre (ACERC), Institute of Advanced Sciences, Yokohama National University kn-affil= affil-num=5 en-affil=Department of Chemistry and Life Science, Yokohama National University kn-affil= affil-num=6 en-affil=Advanced Chemical Energy Research Centre (ACERC), Institute of Advanced Sciences, Yokohama National University kn-affil= affil-num=7 en-affil=Research Institute for Interdisciplinary Science and Department of Chemistry, Okayama University kn-affil= affil-num=8 en-affil=Department of Chemistry and Life Science, Yokohama National University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=202 cd-vols= no-issue=3 article-no= start-page=473 end-page=483 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230909 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Mammography screening has increased the detection of subcentimeter breast cancers. The prognosis for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative T1a/bN0M0 breast cancers is excellent; however, the necessity of adjuvant endocrine therapy (ET) is uncertain.
Methods We evaluated the effectiveness of adjuvant ET in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer who underwent surgery from 2008 to 2012. Standard ET was administrated after surgery. The primary endpoint was the cumulative incidence of distant metastasis. All statistical tests were 2-sided.
Results Adjuvant ET was administered to 3991 (83%) of the 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%], diseases). The median follow-up period was 9.2 years. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32–0.93). In multivariate analysis, the independent risk factors for distant metastasis were no history of ET, mastectomy, high-grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% with and without ET, respectively (adjusted HR, 0.57; 95% CI, 0.39–0.83). In addition, adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs. 6.9%; sHR, 0.17, and 1.9% vs. 5.2%; sHR, 0.33).
Conclusions The prognosis was favorable in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, adjuvant ET reduced the incidence of distant metastasis with minimal absolute risk difference. These findings support considering the omission of adjuvant ET, especially for patients with low-grade and no lymphatic invasion disease. en-copyright= kn-copyright= en-aut-name=SasadaShinsuke en-aut-sei=Sasada en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KondoNaoto en-aut-sei=Kondo en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HashimotoHiroya en-aut-sei=Hashimoto en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiYuko en-aut-sei=Takahashi en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TerataKaori en-aut-sei=Terata en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KidaKumiko en-aut-sei=Kida en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SagaraYasuaki en-aut-sei=Sagara en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UenoTakayuki en-aut-sei=Ueno en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AnanKeisei en-aut-sei=Anan en-aut-mei=Keisei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SutoAkihiko en-aut-sei=Suto en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KanbayashiChizuko en-aut-sei=Kanbayashi en-aut-mei=Chizuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakahashiMina en-aut-sei=Takahashi en-aut-mei=Mina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakamuraRikiya en-aut-sei=Nakamura en-aut-mei=Rikiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IshibaToshiyuki en-aut-sei=Ishiba en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TsuneizumiMichiko en-aut-sei=Tsuneizumi en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NishimuraSeiichiro en-aut-sei=Nishimura en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=NaitoYoichi en-aut-sei=Naito en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IwataHiroji en-aut-sei=Iwata en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University kn-affil= affil-num=2 en-affil=Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=3 en-affil=Core Laboratory, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=4 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Breast and Endocrine Surgery, Akita University Hospital kn-affil= affil-num=6 en-affil=Department of Breast Surgical Oncology, St. Luke’s International Hospital kn-affil= affil-num=7 en-affil=Department of Breast and Thyroid Surgical Oncology, Social medical corporation Hakuaikai, Sagara Hospital kn-affil= affil-num=8 en-affil=Breast Oncology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=9 en-affil=Department of Surgery, Kitakyushu Municipal Medical Center kn-affil= affil-num=10 en-affil=Department of Breast Surgery, National Cancer Center Hospital kn-affil= affil-num=11 en-affil=Department of Breast Oncology, Niigata Cancer Center Hospital kn-affil= affil-num=12 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=13 en-affil=Department of Breast Surgery, Chiba Cancer Center kn-affil= affil-num=14 en-affil=Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=15 en-affil=Department of Breast Surgery, Shizuoka General Hospital kn-affil= affil-num=16 en-affil=Department of Breast Surgery, Shizuoka Cancer Center Hospital kn-affil= affil-num=17 en-affil=Department of General Internal Medicine, National Cancer Center Hospital East kn-affil= affil-num=18 en-affil=Breast Oncology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=19 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=20 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=T1a/b kn-keyword=T1a/b en-keyword=Endocrine therapy kn-keyword=Endocrine therapy en-keyword=Estrogen receptor kn-keyword=Estrogen receptor en-keyword=Prognosis kn-keyword=Prognosis END start-ver=1.4 cd-journal=joma no-vol=141 cd-vols= no-issue= article-no= start-page=106955 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vibriosis in South Asia: A systematic review and meta-analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: South Asia remains home to foodborne diseases caused by the Vibrio species. We aimed to compile and update information on the epidemiology of vibriosis in South Asia.
Methods: For this systematic review and meta-analysis, we searched PubMed, Web of Science, EMBASE, and Google Scholar for studies related to vibriosis in South Asia published up to May 2023. A random-effects meta-analysis was used to estimate the pooled isolation rate of non-cholera-causing Vibrio species.
Results: In total, 38 studies were included. Seven of these were case reports and 22 were included in the meta-analysis. The reported vibriosis cases were caused by non-O1/non-O139 V. cholerae, V. parahaemolyticus, V. fluvialis, and V. vulnificus. The overall pooled isolation rate was 4.0% (95% confidence interval [CI] 3.0-5.0%) in patients with diarrhea. Heterogeneity was high (I-2 = 98.0%). The isolation rate of non-O1/non-O139 V. cholerae, V. parahaemolyticus, and V. fluvialis were 9.0 (95% CI 7.0-10.0%), 1.0 (95% CI 1.0-2.0%), and 2.0 (95% CI: 1.0-3.0%), respectively. Regarding V. parahaemolyticus, O3:K6 was the most frequently isolated serotype. Cases peaked during summer. Several studies reported antibiotic-resistant strains and those harboring extended-spectrum beta-lactamases genes.
Conclusions: This study demonstrates a high burden of infections caused by non-cholera-causing Vibrio species in South Asia. en-copyright= kn-copyright= en-aut-name=MuzemboBasilua Andre en-aut-sei=Muzembo en-aut-mei=Basilua Andre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitaharaKei en-aut-sei=Kitahara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhnoAyumu en-aut-sei=Ohno en-aut-mei=Ayumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KhatiwadaJanuka en-aut-sei=Khatiwada en-aut-mei=Januka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DuttaShanta en-aut-sei=Dutta en-aut-mei=Shanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyoshiShin-Ichi en-aut-sei=Miyoshi en-aut-mei=Shin-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Social Work Institute kn-affil= affil-num=5 en-affil=Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Vibrio parahaemolyticus kn-keyword=Vibrio parahaemolyticus en-keyword=Vibrio vulnificus kn-keyword=Vibrio vulnificus en-keyword=Vibrio mimicus kn-keyword=Vibrio mimicus en-keyword=Vibrio fluvialis kn-keyword=Vibrio fluvialis en-keyword=Seafood kn-keyword=Seafood en-keyword=Gastroenteritis kn-keyword=Gastroenteritis END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue=1 article-no= start-page=31 end-page=37 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230914 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy and safety of olaparib, olaparib plus bevacizumab and niraparib maintenance treatment in Japanese patients with platinum-sensitive advanced ovarian cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: To investigate whether maintenance treatment could be safely and effectively performed with olaparib, olaparib plus bevacizumab and niraparib in platinum-sensitive advanced ovarian cancer at multiple institutions in Japan.
Methods: We investigated progression-free survival and adverse events in 117 patients with platinum-sensitive advanced ovarian cancer treated with maintenance therapy.
Results: The median progression-free survival of 117 patients was 20.1 months. Patients with germline BRCA pathogenic variants had a significantly better prognosis than the other groups (P < 0.001). Furthermore, in the multivariate analysis, stage IV (P = 0.016) and germline BRCA wild-type (P ≤ 0.001) were significantly associated with worse progression-free survival in patients with advanced ovarian cancer. Regarding adverse events, all three types of maintenance treatment were significantly worse than chemotherapy given before maintenance treatment with respect to renal function (olaparib, P = 0.037; olaparib plus bevacizumab, P < 0.001; and niraparib, P = 0.016).
Conclusion: Maintenance treatment was performed effectively and safely. Renal function deterioration is likely to occur during maintenance treatment, and careful administration is important in platinum-sensitive advanced ovarian cancer. en-copyright= kn-copyright= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuokaHirofumi en-aut-sei=Matsuoka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YorimitsuMasae en-aut-sei=Yorimitsu en-aut-mei=Masae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OgawaMariko en-aut-sei=Ogawa en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanemoriMiho en-aut-sei=Kanemori en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SueokaKotaro en-aut-sei=Sueoka en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KozaiAyumi en-aut-sei=Kozai en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraHiroko en-aut-sei=Nakamura en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HarumaTomoko en-aut-sei=Haruma en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShiroyamaYuko en-aut-sei=Shiroyama en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayataYuu en-aut-sei=Hayata en-aut-mei=Yuu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SugiiHirokazu en-aut-sei=Sugii en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UedaAkiko en-aut-sei=Ueda en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KuriharaShuichi en-aut-sei=Kurihara en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=UrayamaSaiko en-aut-sei=Urayama en-aut-mei=Saiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimizuMiyuki en-aut-sei=Shimizu en-aut-mei=Miyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, City Hiroshima Citizens Hospital kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, National Organization Fukuyama Medical Center kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Fukuyama City Hospital kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Perinatology and Gynecology, Kagawa University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, National Hospital Organization KURE Medical Center and Chugoku Cancer Center kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Saiseikai General Hospital kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Prefectural Hospital kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital kn-affil= affil-num=12 en-affil=Department of Obstetrics and Gynecology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=13 en-affil=Department of Obstetrics and Gynecology, Onomichi General Hospital kn-affil= affil-num=14 en-affil=Department of Obstetrics and Gynecology, Japanese Red Cross Matsuyama Hospital kn-affil= affil-num=15 en-affil=Department of Obstetrics and Gynecology, Higashi Hiroshima Medical Center kn-affil= affil-num=16 en-affil=Department of Obstetrics and Gynecology, Kagawa Rosai Hospital kn-affil= affil-num=17 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=olaparib kn-keyword=olaparib en-keyword=olaparib plus bevacizumab kn-keyword=olaparib plus bevacizumab en-keyword=niraparib kn-keyword=niraparib en-keyword=renal function kn-keyword=renal function END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=6 article-no= start-page=804 end-page=815 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neoadjuvant chemotherapy followed by interval debulking surgery for advanced epithelial ovarian cancer: GOTIC-019 study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Three randomized controlled trials have resulted in extremely extensive application of the strategy of using neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for patients with advanced epithelial ovarian cancer in Japan. This study aimed to evaluate the status and effectiveness of treatment strategies using NAC followed by IDS in Japanese clinical practice.
Patients and methods We conducted a multi-institutional observational study of 940 women with Federation of Gynecology and Obstetrics (FIGO) stages III–IV epithelial ovarian cancer treated at one of nine centers between 2010 and 2015. Progression-free survival (PFS) and overall survival (OS) were compared between 486 propensity-score matched participants who underwent NAC followed by IDS and primary debulking surgery (PDS) followed by adjuvant chemotherapy.
Results Patients with FIGO stage IIIC receiving NAC had a shorter OS (median OS: 48.1 vs. 68.2 months, hazard ratio [HR]: 1.34; 95% confidence interval [CI] 0.99–1.82, p = 0.06) but not PFS (median PFS: 19.7 vs. 19.4 months, HR: 1.02; 95% CI: 0.80–1.31, p = 0.88). However, patients with FIGO stage IV receiving NAC and PDS had comparable PFS (median PFS: 16.6 vs. 14.7 months, HR: 1.07 95% CI: 0.74–1.53, p = 0.73) and OS (median PFS: 45.2 vs. 35.7 months, HR: 0.98; 95% CI: 0.65–1.47, p = 0.93).
Conclusions NAC followed by IDS did not improve survival. In patients with FIGO stage IIIC, NAC may be associated with a shorter OS. en-copyright= kn-copyright= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TamuraJun en-aut-sei=Tamura en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShibutaniTakashi en-aut-sei=Shibutani en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiwaMaiko en-aut-sei=Miwa en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoTomoyasu en-aut-sei=Kato en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShikamaAyumi en-aut-sei=Shikama en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeiYuji en-aut-sei=Takei en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KamiyaNatsuko en-aut-sei=Kamiya en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=InoueNaoki en-aut-sei=Inoue en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakamuraKazuto en-aut-sei=Nakamura en-aut-mei=Kazuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=InoueAya en-aut-sei=Inoue en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamamotoKoji en-aut-sei=Yamamoto en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraKeiichi en-aut-sei=Fujiwara en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SuzukiMitsuaki en-aut-sei=Suzuki en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biostatistics, Yokohama City University School of Medicine kn-affil= affil-num=3 en-affil=Department of Gynecologic Oncology, Hyogo Cancer Center kn-affil= affil-num=4 en-affil=Department of Gynecologic Oncology, Saitama Medical University International Medical Center kn-affil= affil-num=5 en-affil=Department of Gynecologic Oncology, National Cancer Center Hospital kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Graduate School of Comprehensive Human Sciences, University of Tsukuba kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Jichi Medical University kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Yokohama City University School of Medicine kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Gunma University kn-affil= affil-num=10 en-affil=Department of Gynecologic Oncology, Gunma Prefectural Cancer Center kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Ehime University School of Medicine kn-affil= affil-num=12 en-affil=Department of Biostatistics, Yokohama City University School of Medicine kn-affil= affil-num=13 en-affil=Department of Gynecologic Oncology, Saitama Medical University International Medical Center kn-affil= affil-num=14 en-affil=Department of Obstetrics and Gynecology, Shin-Yurigaoka General Hospital kn-affil= en-keyword=Neoadjuvant chemotherapy kn-keyword=Neoadjuvant chemotherapy en-keyword=Epithelial ovarian cancer kn-keyword=Epithelial ovarian cancer en-keyword=Adjuvant chemotherapy kn-keyword=Adjuvant chemotherapy en-keyword=Interval debulking surgery kn-keyword=Interval debulking surgery en-keyword=Primary debulking surgery kn-keyword=Primary debulking surgery END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=12 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231214 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Complete genomic sequence of Vibrio fluvialis strain IDH5335 isolated from a patient with diarrhea in Kolkata, India en-subtitle= kn-subtitle= en-abstract= kn-abstract=We isolated a Vibrio fluvialis strain (IDH5335) from a stool sample collected from a patient with diarrhea. In this announcement, we report the complete genomic sequence of this organism, which was obtained by combining Illumina and Oxford Nanopore sequencing data. en-copyright= kn-copyright= en-aut-name=ChowdhuryGoutam en-aut-sei=Chowdhury en-aut-mei=Goutam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitaharaKei en-aut-sei=Kitahara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaniguchiMakoto en-aut-sei=Taniguchi en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UesakaKazuma en-aut-sei=Uesaka en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MuzemboBasilua Andre en-aut-sei=Muzembo en-aut-mei=Basilua Andre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitraDebmalya en-aut-sei=Mitra en-aut-mei=Debmalya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhnoAyumu en-aut-sei=Ohno en-aut-mei=Ayumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=RamamurthyThandavarayan en-aut-sei=Ramamurthy en-aut-mei=Thandavarayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DuttaShanta en-aut-sei=Dutta en-aut-mei=Shanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MukhopadhyayAsish Kumar en-aut-sei=Mukhopadhyay en-aut-mei=Asish Kumar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Collaborative Research Center of Okayama University for Infectious Diseases in India at ICMR-NICED kn-affil= affil-num=2 en-affil=Collaborative Research Center of Okayama University for Infectious Diseases in India at ICMR-NICED kn-affil= affil-num=3 en-affil=Oral Microbiome Center, Taniguchi Dental Clinic kn-affil= affil-num=4 en-affil=Graduate School of Bioagricultural Sciences, Nagoya University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Collaborative Research Center of Okayama University for Infectious Diseases in India at ICMR-NICED kn-affil= affil-num=7 en-affil=Collaborative Research Center of Okayama University for Infectious Diseases in India at ICMR-NICED kn-affil= affil-num=8 en-affil=ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=9 en-affil=ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=10 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=ICMR-National Institute of Cholera and Enteric Diseases kn-affil= en-keyword=Vibrio fluvialis kn-keyword=Vibrio fluvialis en-keyword=diarrhea kn-keyword=diarrhea en-keyword=bacteria kn-keyword=bacteria en-keyword=genome kn-keyword=genome END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=2 article-no= start-page=201 end-page=204 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Gallbladder Cancer with Trousseau Syndrome Successfully Treated Using Radical Resection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Trousseau syndrome is characterized by cancer-associated systemic thrombosis. We describe the first case of a successfully treated gallbladder adenocarcinoma accompanied by Trousseau syndrome. A 66-year-old woman presented with right hemiplegia. Magnetic resonance imaging identified multiple cerebral infarctions. Her serum carbohydrate antigen 19-9 and D-dimer levels were markedly elevated, and a gallbladder tumor was detected via abdominal computed tomography. Venous ultrasonography of the lower limbs revealed a deep venous thrombus in the right peroneal vein. These findings suggested that the brain infarctions were likely caused by Trousseau syndrome associated with her gallbladder cancer. Radical resection of the gallbladder tumor was performed. The resected gallbladder was filled with mucus and was pathologically diagnosed as an adenocarcinoma. Her postoperative course was uneventful, and she received a one-year course of adjuvant therapy with oral S-1. No cancer recurrence or thrombosis was noted 26 months postoperatively. Despite concurrent Trousseau syndrome, a radical cure of the primary tumor and thrombosis could be achieved with the appropriate treatment. en-copyright= kn-copyright= en-aut-name=MasunagaAkari en-aut-sei=Masunaga en-aut-mei=Akari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TabuchiMotoyasu en-aut-sei=Tabuchi en-aut-mei=Motoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakamotoShinya en-aut-sei=Sakamoto en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshimatsuRika en-aut-sei=Yoshimatsu en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoManabu en-aut-sei=Matsumoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwataJun en-aut-sei=Iwata en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkabayashiTakehiro en-aut-sei=Okabayashi en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=4 en-affil=Department of Radiology, Kochi Health Sciences Center kn-affil= affil-num=5 en-affil=Department of Radiology, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= en-keyword=gallbladder cancer kn-keyword=gallbladder cancer en-keyword=Trousseau syndrome kn-keyword=Trousseau syndrome en-keyword=radical surgery kn-keyword=radical surgery END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=2 article-no= start-page=95 end-page=106 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Roles of Neuropeptide Y in Respiratory Disease Pathogenesis via the Airway Immune Response en-subtitle= kn-subtitle= en-abstract= kn-abstract=The lungs are very complex organs, and the respiratory system performs the dual roles of repairing tissue while protecting against infection from various environmental stimuli. Persistent external irritation disrupts the immune responses of tissues and cells in the respiratory system, ultimately leading to respiratory disease. Neuropeptide Y (NPY) is a 36-amino-acid polypeptide and a neurotransmitter that regulates homeostasis. The NPY receptor is a seven-transmembrane-domain G-protein-coupled receptor with six subtypes (Y1, Y2, Y3, Y4, Y5, and Y6). Of these receptors, Y1, Y2, Y4, and Y5 are functional in humans, and Y1 plays important roles in the immune responses of many organs, including the respiratory system. NPY and the Y1 receptor have critical roles in the pathogenesis of asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis. The effects of NPY on the airway immune response and pathogenesis differ among respiratory diseases. This review focuses on the involvement of NPY in the airway immune response and pathogenesis of various respiratory diseases. en-copyright= kn-copyright= en-aut-name=ItanoJunko en-aut-sei=Itano en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyaharaNobuaki en-aut-sei=Miyahara en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=neuropeptide y kn-keyword=neuropeptide y en-keyword=Y1 receptor kn-keyword=Y1 receptor en-keyword=airway immune response kn-keyword=airway immune response en-keyword=bronchial epithelial cells kn-keyword=bronchial epithelial cells en-keyword=respiratory disease kn-keyword=respiratory disease END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3 article-no= start-page=243 end-page=253 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=GSK-3α/β and MEK inhibitors assist the microenvironment of tumor initiation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Induced pluripotent stem cells (iPSCs) are useful tools for modeling diseases and developing personalized medicine. We have been developing cancer stem cells (CSCs) from iPSCs with conditioned medium (CM) of cancer-derived cells as the mimicry of the microenvironment of tumor initiation. However, the conversion of human iPSCs has not always been efficient with only CM. In this study, human iPSCs reprogrammed from monocytes of healthy volunteers were cultured in a media containing 50% of the CM from human pancreatic cancer derived BxPC3 cells supplemented with a MEK inhibitor (AZD6244) and a GSK-3α/β inhibitor (CHIR99021). The survived cells were assessed for the characteristics of CSCs in vitro and in vivo. As a result, they exhibited CSC phenotypes of self-renewal, differentiation, and malignant tumorigenicity. Primary culture of the malignant tumors of the converted cells exhibited the elevated expression of CSC related genes CD44, CD24 and EPCAM maintaining the expression of stemness genes. In conclusion, the inhibition of GSK-3α/β and MEK and the microenvironment of tumor initiation mimicked by the CM can convert human normal stem cells into CSCs. This study could provide insights into establishing potentially novel personalized cancer models which could help investigate the tumor initiation and screening of personalized therapies on CSCs. en-copyright= kn-copyright= en-aut-name=HassanGhmkin en-aut-sei=Hassan en-aut-mei=Ghmkin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AfifySaid M. en-aut-sei=Afify en-aut-mei=Said M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZahraMaram H. en-aut-sei=Zahra en-aut-mei=Maram H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NawaraHend M. en-aut-sei=Nawara en-aut-mei=Hend M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KumonKazuki en-aut-sei=Kumon en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwasakiYoshiaki en-aut-sei=Iwasaki en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SalomonDavid S. en-aut-sei=Salomon en-aut-mei=David S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SenoAkimasa en-aut-sei=Seno en-aut-mei=Akimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SenoMasaharu en-aut-sei=Seno en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University kn-affil= affil-num=2 en-affil=Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University kn-affil= affil-num=3 en-affil=Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University kn-affil= affil-num=4 en-affil=Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University kn-affil= affil-num=5 en-affil=Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University kn-affil= affil-num=6 en-affil=Health Service Center, Okayama University kn-affil= affil-num=7 en-affil=Center for Cancer Research, National Cancer Institute kn-affil= affil-num=8 en-affil=Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University kn-affil= affil-num=9 en-affil=Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University kn-affil= en-keyword=Cancer stem cells kn-keyword=Cancer stem cells en-keyword=Human iPSCs kn-keyword=Human iPSCs en-keyword=Signal pathway inhibitors kn-keyword=Signal pathway inhibitors en-keyword=Tumor initiation kn-keyword=Tumor initiation END