start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=2 article-no= start-page=e70251 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Muscle Atrophy-Related Adverse Events of Antidiabetic Drug Classes: A Pharmacovigilance Analysis Using VigiBase Data en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Diabetes mellitus?a chronic metabolic disorder associated with an increased risk of muscle atrophy?can significantly impact patients' quality of life and overall health outcomes. While antidiabetic medications are crucial for managing blood glucose levels, some have been linked to muscle-related adverse events, potentially exacerbating the already elevated risk of muscle deterioration in diabetic patients. However, a comprehensive analysis of muscle atrophy-related adverse events across different classes of antidiabetic drugs has been lacking. Therefore, this study investigates the profile of muscle atrophy-related adverse events across major antidiabetic drug classes using the World Health Organization's (WHO's) Individual Case Safety Reports database.
Methods: A pharmacovigilance analysis was conducted using data from VigiBase, the WHO's global reporting database, from 1968 to September 2025. The study examined adverse event signals related to muscle atrophy, sarcopenia, muscular weakness and motor function decline for nine classes of antidiabetic medications. Reporting odds ratios (RORs) were calculated to assess signal detection, and co-occurrence patterns of adverse events were analysed.
Results: Among 41?551?306 adverse event reports, 2?095?847 were related to antidiabetic medications. Safety signals for muscle atrophy were detected with sulfonylureas (ROR: 1.2, 95% CI: 1.01?1.43, p?=?0.042), GLP-1 analogues (ROR: 1.2, 95% CI: 1.02?1.41, p?=?0.031) and SGLT2 inhibitors (ROR: 1.5, 95% CI: 1.19?1.78, p? Conclusions: These findings indicate notable differences in the profiles of muscle atrophy?related adverse events among major classes of antidiabetic drugs, suggesting that drug selection may influence the risk of muscle function decline in patients. Clinicians should consider these safety profiles when prescribing antidiabetic therapies; however, causal relationships cannot be inferred solely from pharmacovigilance data. Further studies are warranted to establish causality between antidiabetic drug use and muscle-related adverse events and to elucidate the underlying mechanisms. en-copyright= kn-copyright= en-aut-name=UetaShiho en-aut-sei=Ueta en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NiimuraTakahiro en-aut-sei=Niimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GodaMitsuhiro en-aut-sei=Goda en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshidaTomoaki en-aut-sei=Ishida en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwataNaohiro en-aut-sei=Iwata en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawadaKei en-aut-sei=Kawada en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyataKoji en-aut-sei=Miyata en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AizawaFuka en-aut-sei=Aizawa en-aut-mei=Fuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YagiKenta en-aut-sei=Yagi en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=ChumaMasayuki en-aut-sei=Chuma en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Izawa]IshizawaYuki en-aut-sei=Izawa]Ishizawa en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=IshizawaKeisuke en-aut-sei=Ishizawa en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= affil-num=2 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= affil-num=3 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= affil-num=4 en-affil=Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=5 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= affil-num=8 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= affil-num=9 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= affil-num=10 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= affil-num=11 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hospital Pharmacy and Pharmacology, Asahikawa Medical University kn-affil= affil-num=13 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= affil-num=14 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= en-keyword=antidiabetic drug kn-keyword=antidiabetic drug en-keyword=muscle atrophy kn-keyword=muscle atrophy en-keyword=sarcopenia kn-keyword=sarcopenia en-keyword=VigiBase kn-keyword=VigiBase 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=20260407 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ROWVA: A Structure-Based Metric for Predicting the Pathogenicity of Protein Variants Using Alphafold2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=p53, an important tumor suppressor protein, functions as a tetramer. Therefore, malignant variants in the tetramer-forming domain increase the likelihood of p53 dysfunction. Recent developments in genome analysis technology have expanded our understanding of malignant variants. However, variants of uncertain significance are also being increasingly identified. Hence, methods to assess the pathogenicity of these variants are required. In this study, we aimed to examine whether AlphaFold2 can be used to evaluate the functional impacts of p53 variants based on predicted three-dimensional (3D) structural information. For each variant present in datasets of p53 functional score, we performed 3D structural prediction using AlphaFold2. We analyzed the correlations among multiple AlphaFold2-derived scores to predict functional scores, such as protein stability and pathogenicity labels, for each dataset. The root-mean-square deviation obtained by comparing the 3D structures predicted by AlphaFold2 for the wild-type and variant structures showed a high correlation with each functional score. Overall, these findings indicate that AlphaFold2 can be used to evaluate variants. en-copyright= kn-copyright= en-aut-name=FurutaniTaiki en-aut-sei=Furutani en-aut-mei=Taiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkushaYuka en-aut-sei=Okusha en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagamiHiroki en-aut-sei=Nagami en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HanafusaHiroko en-aut-sei=Hanafusa en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=SawadaRyusuke en-aut-sei=Sawada en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= affil-num=1 en-affil=Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine kn-affil= en-keyword=3D protein structural prediction kn-keyword=3D protein structural prediction en-keyword=AlphaFold2 kn-keyword=AlphaFold2 en-keyword=p53 kn-keyword=p53 en-keyword=tumor suppressor kn-keyword=tumor suppressor en-keyword=variants of uncertain significance kn-keyword=variants of uncertain significance END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=5 article-no= start-page=2741 end-page=2748 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Global trends in systemic sclerosis-related mortality, 2001?2023: an epidemiological analysis using World Health Organization mortality data en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives This study aimed to evaluate the global trends in systemic sclerosis (SSc)-related mortality by age, sex, and geographic region. SSc is a multisystem autoimmune disease characterized by tissue fibrosis, vascular dysfunction, and multi-organ involvement, which is associated with a high mortality risk.
Methods Using the World Health Organization Mortality Database, we examined trends in SSc-related crude mortality rates (SSc-CRs) and age-standardized mortality rates (SSc-ASMR) per 1,000,000 population from 2001 to 2023. Locally weighted regression was applied to visualize long-term patterns, and Joinpoint regression was used to assess the national trends from 2010 to 2023.
Results Across 74 countries, 85,291 SSc-related deaths were reported, with 79.41% occurring in females. The SSc-CR steadily increased from 1.97 (95% confidence interval [CI]: 1.71?2.23) in 2001 to 2.34 (95% CI: 2.01?2.68) in 2023, while the SSc-ASMR decreased from 1.58 (95% CI: 1.42?1.74) to 1.29 (95% CI: 1.08?1.50), respectively. Regionally, mortality was the highest in the Western Pacific region and declined in the Americas and Europe, with temporal fluctuations. The SSc-ASMR was highest in countries with a middle sociodemographic index (SDI).
Conclusions While overall age-standardized mortality from SSc has declined in many regions, disparities persist. These results underscore the importance of sustaining research and enhancing disease awareness, as well as developing strategies to reduce mortality in high-risk populations and regions. en-copyright= kn-copyright= en-aut-name=BelangoyKeith Pardillada en-aut-sei=Belangoy en-aut-mei=Keith Pardillada kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaKo en-aut-sei=Harada en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=VuQuynh Thi en-aut-sei=Vu en-aut-mei=Quynh Thi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OuddoudHanane en-aut-sei=Ouddoud en-aut-mei=Hanane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LescanoJudah Israel Ong en-aut-sei=Lescano en-aut-mei=Judah Israel Ong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoMichio en-aut-sei=Yamamoto en-aut-mei=Michio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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=12 ORCID= affil-num=1 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Division of Haematology and Oncology, Mayo Clinic, Rochester kn-affil= affil-num=3 en-affil=Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=4 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Human Sciences, The University of Osaka kn-affil= affil-num=9 en-affil=Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= en-keyword=Age-standardized mortality rate kn-keyword=Age-standardized mortality rate en-keyword=Global health kn-keyword=Global health en-keyword=Mortality trends kn-keyword=Mortality trends en-keyword=Sociodemographic index kn-keyword=Sociodemographic index en-keyword=Systemic sclerosis kn-keyword=Systemic sclerosis 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=113 cd-vols= no-issue=4 article-no= start-page=043713 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260408 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Analytical and numerical studies of periodic superradiance en-subtitle= kn-subtitle= en-abstract= kn-abstract=We conduct a theoretical study to understand the periodic superradiance observed in an Er:YSO crystal. First, we construct a model based on the Maxwell-Bloch equations for a reduced level system, a pair of superradiance states, and a population reservoir state. Analysis of the eigenvalues of the linearized differential equations shows that periodic superradiance can be realized only for certain parameters. We also derive two-variable equations consisting of the coherence and population difference between the two superradiance states, which contain the essential feature of the periodic superradiance. The two-variable equations clarify the mathematical structure of this periodic phenomenon and give analytical forms of the period, pulse duration, and number of emitted photons. Our model successfully reproduces the periodic behavior, but the actual experimental parameters are found to be outside the parameter region for the periodic superradiance. This result implies that some other mechanism(s) is (are) required. As one example, assuming that the field decay rate varies with the electric field, the periodic superradiance can be reproduced even under the actual experimental conditions. en-copyright= kn-copyright= en-aut-name=HaraHideaki en-aut-sei=Hara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyamotoYuki en-aut-sei=Miyamoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HanJunseok en-aut-sei=Han en-aut-mei=Junseok kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OmotoRiku en-aut-sei=Omoto en-aut-mei=Riku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImaiYasutaka en-aut-sei=Imai en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= en-aut-name=YoshimuraMotohiko en-aut-sei=Yoshimura en-aut-mei=Motohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=5 en-affil=Research Institute for Interdisciplinary Science, Okayama 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= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=11550 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260302 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pseudohypoxia induced by iron chelators preserves working memory performance in aged mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pseudohypoxia refers to a physiological condition wherein hypoxia-inducible factor (HIF) is pharmacologically upregulated under normoxia, thereby modulating immune responses. We hypothesized that pseudohypoxia, induced by iron chelators, may similarly potentiate systemic immune responses in aged mice, concurrently triggering neuro-regenerative signaling pathways and enhancing cognitive performance. In this study, aged mice (43?48 weeks old) were orally administered two iron chelators, Super Polyphenol 10 (SP10) or Roxadustat, to induce a pseudohypoxia. An 8-week oral regimen of SP10 and Roxadustat significantly preserved working memory, as assessed by the Y-maze test (YMT). White blood cell counts and hippocampal volume, as assessed by magnetic resonance imaging (MRI), were elevated in the treatment groups relative to controls. Pseudohypoxia induced by SP10 tended to enhance neuro-regenerative signaling, specifically involving the Tau and JNK pathways, and potentially modulated Doublecortin (DCX) expression, although statistical significance was limited by sample size. Importantly, inflammatory markers, such as ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP), were not elevated by treatment. Collectively, these findings suggest that pseudohypoxia induced by iron chelators preserves working memory performance accompanied by leukocytosis, without concomitant neuroinflammation. en-copyright= kn-copyright= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KasaiTomonari en-aut-sei=Kasai en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=KomakiShiho en-aut-sei=Komaki en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HamadaYusuke en-aut-sei=Hamada en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Health Service Section, Environment Health & Safety Intelligence Department, Okayama University kn-affil= affil-num=3 en-affil=Department of Applied Energy, Graduate School of Engineering, Nagoya University kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Hypoxia-inducible factor kn-keyword=Hypoxia-inducible factor en-keyword=Working memory kn-keyword=Working memory en-keyword=Hippocampus kn-keyword=Hippocampus en-keyword=Iron kn-keyword=Iron END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=4 article-no= start-page=1769 end-page=1784 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=P53-armed Oncolytic Adenovirus Enhances the Efficacy of PD-1 Blockade in Neuroblastoma by Inducing Immunogenic Cell Death en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system. Although immunotherapy with immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) has emerged as novel antitumor therapy, high-risk NB tumors are refractory to ICI therapy. Oncolytic virotherapy is expected to potentiate the antitumor immune response by inducing immunogenic cell death (ICD). In the present study, we assessed the therapeutic potential of OBP-301 and OBP-702, telomerase-specific oncolytic adenoviruses, for the induction of ICD and combined effect with PD-1 blockade against NB cells.
Materials and Methods: The cytopathic activity of OBP-301 and OBP-702 was assessed using three human MYCN-amplified NB cell lines (IMR-32, LA-N-5, and NB-1) and a murine non-MYCN-amplified NB cell line (Neuro-2a). Virus-mediated antitumor effect was assessed by analyzing cell viability, secretion of extracellular adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1), apoptosis, autophagy, and PD-L1 levels. A subcutaneous Neuro-2a tumor model was used to evaluate the in vivo antitumor effect of combination therapy with OBP-702 and anti-PD-1 antibody.
Results: OBP-702 exhibited stronger cytopathic activity, inducing ICD with secretion of ATP and HMGB1, compared to OBP-301 in human and murine NB cells. OBP-301 and OBP-702 increased apoptosis, autophagy, and PD-L1 expression in murine NB cells. Moreover, OBP-702 significantly prolonged the survival of tumor-bearing mice compared to monotherapy with PD-1 blockade.
Conclusion: OBP-702 is a promising antitumor strategy to promote the antitumor effect of ICIs by inducing ICD against NB tumors. en-copyright= kn-copyright= en-aut-name=TANIMORIMICHI en-aut-sei=TANI en-aut-mei=MORIMICHI 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=NOUSOHIROSHI en-aut-sei=NOUSO en-aut-mei=HIROSHI 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=URATAYASUO en-aut-sei=URATA en-aut-mei=YASUO 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=NODATAKUO en-aut-sei=NODA en-aut-mei=TAKUO 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=FUJIWARATOSHIYOSHI en-aut-sei=FUJIWARA en-aut-mei=TOSHIYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=Oncolys BioPharma, Inc. 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 Pediatric 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= en-keyword=Neuroblastoma kn-keyword=Neuroblastoma en-keyword=oncolytic adenovirus kn-keyword=oncolytic adenovirus en-keyword=p53 kn-keyword=p53 en-keyword=immunogenic cell death kn-keyword=immunogenic cell death en-keyword=PD-1 kn-keyword=PD-1 END start-ver=1.4 cd-journal=joma no-vol=264 cd-vols= no-issue= article-no= start-page=128798 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Improving thermal stability of a microcavity emitter for utilization under atmospheric environment en-subtitle= kn-subtitle= en-abstract= kn-abstract=With the development of micro-fabrication technology, various metamaterials with controlled emission spectra have been proposed as thermal emitters. However, general metamaterials have a risk of deformations and degradation at high temperatures in atmospheric conditions, which is inconvenient for use as a thermal emitter. In this study, we propose a concept to enhance the thermal durability of microcavity-type metamaterials. Although typical microcavities are entirely composed of metal to excite the resonance of electromagnetic waves, we assessed the feasibility of a microcavity consisting of silicon with minimal metal coatings. While usual metals are oxidized at high temperatures, gold is rarely oxidized due to its chemical stability. However, the gold layer deposited on the Si substrate has the potential to melt below 400 C due to the formation of an Au-Si eutectic alloy, which has a much lower melting point than pure gold. Therefore, we focused on the gold-tungsten bilayer as a suitable metal coating for the silicon microcavity, thereby preventing oxidation and melting that would otherwise influence the emission spectra of the thermal emitter. The numerical analysis ensured that the proposed microcavity exhibited electromagnetic resonance, similar to that of a microcavity entirely composed of metal, unless the metal coating was too thin. The fabricated microcavity with the gold-tungsten coating also exhibited a thermal emission within a limited wavelength range, due to the microcavity resonance. Moreover, the heating experiment revealed that the microcavity with a gold-tungsten coating maintained its emissivity even when heated to 400 C, which is higher than the oxidation point of tungsten and the melting point of the Au-Si eutectic alloy. Consequently, the gold-tungsten coating would be a reasonable approach to improve the stability of the microcavity-type metamaterial at high temperatures under oxidative conditions. en-copyright= kn-copyright= en-aut-name=IsobeKazuma en-aut-sei=Isobe en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MorishigeShota en-aut-sei=Morishige en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoTaiyo en-aut-sei=Sato en-aut-mei=Taiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamadaYutaka en-aut-sei=Yamada en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HoribeAkihiko en-aut-sei=Horibe en-aut-mei=Akihiko 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School 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=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Metamaterial kn-keyword=Metamaterial en-keyword=Microcavity emitter kn-keyword=Microcavity emitter en-keyword=Emissivity spectrum kn-keyword=Emissivity spectrum en-keyword=Thermal stability kn-keyword=Thermal stability en-keyword=Tungsten oxidation kn-keyword=Tungsten oxidation en-keyword=Eutectic melting kn-keyword=Eutectic melting END start-ver=1.4 cd-journal=joma no-vol=283 cd-vols= no-issue=2 article-no= start-page=78 end-page= 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=The Simons Observatory: Detector Polarization Angle Calibration Using a Sparse Wire Grid with Initial Datasets of the Small-aperture Telescopes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Improved measurements of B-modes in the cosmic microwave background can be obtained through accurate calibration of the orientation of detector antennas as projected onto the sky. Miscalibration of the detector polarization angle leads to a leakage of E-modes into B-modes, which can bias the detection of the latter. To achieve a (r) of 0.003, the Simons Observatory small-aperture telescopes are required to calibrate the global polarization angle on the sky with an accuracy ?0.1. We demonstrate a fully remote-controllable calibration system using a gsparse wire grid,h which injects a rotatable linear polarized signal across the telescopefs focal plane. This calibration system is installed and operational on one of the small-aperture telescopes at its observing site at the Parque Astron?mico in the Atacama desert in Chile. We developed a pipeline for the detector polarization angle calibration, and demonstrate it using initial data for 93 and 145 GHz frequency bands. The observed distribution of detector polarization angles is in agreement with the instrument design. Statistical uncertainties for the relatively calibrated polarization angles are 0.02 and 0.03 at 93 and 145 GHz, respectively. Systematic uncertainty was evaluated to be 0.08 at the hardware development and fabrication stage. Their sum in quadrature is less than 0.1. en-copyright= kn-copyright= en-aut-name=NakataHironobu en-aut-sei=Nakata en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AdachiShunsuke en-aut-sei=Adachi en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaKyohei en-aut-sei=Yamada en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=RandallMichael en-aut-sei=Randall en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KasaiYutaro en-aut-sei=Kasai en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ArnoldKam en-aut-sei=Arnold en-aut-mei=Kam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BixlerBryce en-aut-sei=Bixler en-aut-mei=Bryce kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ChinoneYuji en-aut-sei=Chinone en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=CrowleyKevin T. en-aut-sei=Crowley en-aut-mei=Kevin T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=DachlythraNadia en-aut-sei=Dachlythra en-aut-mei=Nadia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=Day-WeissSamuel en-aut-sei=Day-Weiss en-aut-mei=Samuel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GalitzkiNicholas en-aut-sei=Galitzki en-aut-mei=Nicholas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=GiardielloSerena en-aut-sei=Giardiello en-aut-mei=Serena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=JohnsonBradley R. en-aut-sei=Johnson en-aut-mei=Bradley R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KeatingBrian en-aut-sei=Keating en-aut-mei=Brian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KoopmanBrian J. en-aut-sei=Koopman en-aut-mei=Brian J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KusakaAkito en-aut-sei=Kusaka en-aut-mei=Akito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=LashnerJack en-aut-sei=Lashner en-aut-mei=Jack kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=NatiFederico en-aut-sei=Nati en-aut-mei=Federico kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=PageLyman en-aut-sei=Page en-aut-mei=Lyman kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=SasakiDaichi en-aut-sei=Sasaki en-aut-mei=Daichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=SuenoYoshinori en-aut-sei=Sueno en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SuzukiJunya en-aut-sei=Suzuki en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TajimaOsamu en-aut-sei=Tajima en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=TsanTran en-aut-sei=Tsan en-aut-mei=Tran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= affil-num=1 en-affil=Department of Physics, Faculty of Science, Kyoto University kn-affil= affil-num=2 en-affil=Okayama University, Department of Physics kn-affil= affil-num=3 en-affil=Joseph Henry Laboratories of Physics, Jadwin Hall, Princeton University kn-affil= affil-num=4 en-affil=Joseph Henry Laboratories of Physics, Jadwin Hall, Princeton University kn-affil= affil-num=5 en-affil=Department of Physics, Faculty of Science, Kyoto University kn-affil= affil-num=6 en-affil=Joseph Henry Laboratories of Physics, Jadwin Hall, Princeton University kn-affil= affil-num=7 en-affil=Department of Physics, University of California San Diego kn-affil= affil-num=8 en-affil=QUP (WPI), KEK kn-affil= affil-num=9 en-affil=Joseph Henry Laboratories of Physics, Jadwin Hall, Princeton University kn-affil= affil-num=10 en-affil=Department of Physics, University of Milano-Bicocca kn-affil= affil-num=11 en-affil=Joseph Henry Laboratories of Physics, Jadwin Hall, Princeton University kn-affil= affil-num=12 en-affil=Department of Physics, University of Texas at Austin kn-affil= affil-num=13 en-affil=School of Physics and Astronomy, Cardiff University kn-affil= affil-num=14 en-affil=University of Virginia, Department of Astronomy kn-affil= affil-num=15 en-affil=Department of Physics, University of California San Diego kn-affil= affil-num=16 en-affil=Wright Laboratory, Department of Physics, Yale University kn-affil= affil-num=17 en-affil=Kavli IPMU (WPI), UTIAS, The University of Tokyo kn-affil= affil-num=18 en-affil=Wright Laboratory, Department of Physics, Yale University kn-affil= affil-num=19 en-affil=Department of Physics, University of Milano-Bicocca kn-affil= affil-num=20 en-affil=Joseph Henry Laboratories of Physics, Jadwin Hall, Princeton University kn-affil= affil-num=21 en-affil=Department of Physics, The University of Tokyo kn-affil= affil-num=22 en-affil=Joseph Henry Laboratories of Physics, Jadwin Hall, Princeton University kn-affil= affil-num=23 en-affil=Department of Physics, Faculty of Science, Kyoto University kn-affil= affil-num=24 en-affil=Department of Physics, Faculty of Science, Kyoto University kn-affil= affil-num=25 en-affil=Physics Division, Lawrence Berkeley National Laboratory kn-affil= END start-ver=1.4 cd-journal=joma no-vol=220 cd-vols= no-issue=3 article-no= start-page=29 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Knot surgered elliptic surfaces without 1- and 3-handles for a (2, 2h + 1)-torus knot en-subtitle= kn-subtitle= en-abstract= kn-abstract=For any positive integers h and n, we show that a knot surgered elliptic surface E(n)T(2,2h+1) for a (2, 2h + 1)-torus knot T (2, 2h + 1) admits a handle decomposition without 1- and 3-handles using a Kirby diagram derived from a Lefschetz fibration on it. As a corollary, an elliptic surface E(1)2,2h+1 has such a handle decomposition. en-copyright= kn-copyright= en-aut-name=MondenNaoyuki en-aut-sei=Monden en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YabuguchiReo en-aut-sei=Yabuguchi en-aut-mei=Reo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Mathematics, Faculty of Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Mathematics, Faculty of Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=131 cd-vols= no-issue=4 article-no= start-page=e2025JE009432 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Investigating the Detectability of Body Wave Phases From Tidal Ice Cracking Events on Titan With the Dragonfly Short-Period Seismometer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Detecting seismic activity on Saturn's icy moon Titan during the Dragonfly mission could provide crucial information on its internal structure. The geological complexity of the moon's surface suggests significant cyclic tidal deformation, likely leading to the fracturing of the ice shell. Considering realistic source locations and fault geometries, we assess whether a vertical short-period seismometer can detect body waves from a Mw 4.0 icequake. Signal-to-noise ratios are evaluated by comparing the high-frequency content with the expected background noise and instrument capabilities for several ice attenuation scenarios and 1D interior models. Our results indicate that the high-frequency content (?1Hz) of Mw?4.0 tidal-induced icequakes is likely undetectable under the most unfavorable attenuation scenarios and atmospheric conditions. However, seismic signals in the 0.5?1 Hz band?where P wave reflections dominate?may still be observable for events occurring in potential seismically active regions at ?800?1,000 km from the Dragonfly's landing site. These signals could provide constraints on the thickness of Titan's outer ice shell, provided that intrinsic attenuation is low and environmental conditions are favorable. en-copyright= kn-copyright= en-aut-name=DelaroqueL. en-aut-sei=Delaroque en-aut-mei=L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawamuraT. en-aut-sei=Kawamura en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LucasA. en-aut-sei=Lucas en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=RodriguezS. en-aut-sei=Rodriguez en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OnoderaK. en-aut-sei=Onodera en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShiraishiH. en-aut-sei=Shiraishi en-aut-mei=H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamadaR. en-aut-sei=Yamada en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaS. en-aut-sei=Tanaka en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=PanningM. P. en-aut-sei=Panning en-aut-mei=M. P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LorenzR. D. en-aut-sei=Lorenz en-aut-mei=R. D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Universit? Paris Cit?, Institut de Physique du Globe de Paris, CNRS kn-affil= affil-num=2 en-affil=Universit? Paris Cit?, Institut de Physique du Globe de Paris, CNRS kn-affil= affil-num=3 en-affil=Universit? Paris Cit?, Institut de Physique du Globe de Paris, CNRS kn-affil= affil-num=4 en-affil=Universit? Paris Cit?, Institut de Physique du Globe de Paris, CNRS kn-affil= affil-num=5 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=6 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=7 en-affil=The University of Aizu kn-affil= affil-num=8 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=9 en-affil=Jet Propulsion Laboratory, California Institute of Technology kn-affil= affil-num=10 en-affil=The Johns Hopkins University Applied Physics Laboratory kn-affil= en-keyword=body waves kn-keyword=body waves en-keyword=planetary seismology kn-keyword=planetary seismology en-keyword=interior structure kn-keyword=interior structure en-keyword=dragonfly mission kn-keyword=dragonfly mission en-keyword=icy moons kn-keyword=icy moons en-keyword=Titan kn-keyword=Titan END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=4 article-no= start-page=115137 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multifaceted role of POU5F1P1 in regulating its parental stem cell gene, POU5F1 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The human-specific retrogene POU5F1P1 (OCT4-Pseudogene1; OCT4-PG1), derived from stem cell factor POU5F1 (OCT4A), is predicted to encode an OCT4A-like protein; however, its function remains unclear. This study investigated OCT4-PG1 expression, translational control, and its role in endometrial cancer and stem cell regulation. Quantitative analyses revealed that elevated OCT4A, but not OCT4-PG1, expression correlated with clinical risk factors associated with poor prognosis in patients with endometrial cancer. OCT4-PG1 is under strong translational suppression mediated by its untranslated region and does not function as a protein under normal conditions. Instead, it acts as a non-coding RNA that suppresses OCT4A translation. Structural analyses showed that a single amino acid deletion (Gln259) destabilizes the OCT4-PG1 protein, thereby preventing its tumorigenic and transcriptional functions. Nevertheless, OCT4-PG1 forms heterodimers with OCT4A or SOX2, enhancing the regulatory activity of OCT4A. These findings highlight the regulatory role of pseudogenes in cancer and stem cell biology, with implications for therapies targeting OCT4A-related pathways. en-copyright= kn-copyright= en-aut-name=IrieKyohei en-aut-sei=Irie en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KosakaMitsuko en-aut-sei=Kosaka en-aut-mei=Mitsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MizunoNobuhiko en-aut-sei=Mizuno en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OmaeRyo en-aut-sei=Omae en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakataniYoshimasa en-aut-sei=Nakatani en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OoSandi Myat Noe en-aut-sei=Oo en-aut-mei=Sandi Myat Noe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=KawaguchiAyano en-aut-sei=Kawaguchi en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=189 end-page=197 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=Relationship between Maternal Body Composition during Pregnancy and Newborn Birth Weight in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: This study aimed to investigate the changes in maternal body composition during pregnancy in Japanese women and the relationship between maternal body composition and newborn birth weight using pre-pregnancy body mass index (BMI) in all trimesters.
Methods: A total of 1,851 pregnant Japanese women were enrolled in this study. Body composition was measured using TANITA MC-190EM. The associations between newborn birth weight and maternal BMI, fat mass (FM), fat-free mass (FFM), total body water (TBW), muscle mass (MM), FM gain, FFM gain, and weight gain were evaluated.
Results: The participantsf age and pre-pregnancy BMI were 34.1 years and 21.4 kg/m2, respectively. Among the patients, 13.4%, 73.0%, 10.3%, and 3.3% were underweight, average weight, overweight, and obese, respectively. The FM showed no significant change from the second to third trimesters in the underweight, overweight, and obese groups. Moreover, the FM in the overweight and obese groups did not change during any period. The FFM, TBW, and MM significantly increased from the first to second and second to third trimesters. In BMI-stratified multivariate regression analyses, FFM in the normal and overweight groups was positively associated with birth weight, whereas FM gain was negatively associated in the underweight and normal groups. No significant associations were observed in the obese group.
Conclusions: Changes in maternal body composition during pregnancy in Japanese women varied by pre-pregnancy BMI. Associations with birth weight also differed by BMI group. Further prospective studies are needed to confirm these relationships and investigate the mechanisms. en-copyright= kn-copyright= en-aut-name=EtoEriko en-aut-sei=Eto en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatoMasakazu en-aut-sei=Kato en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KirinoSatoe en-aut-sei=Kirino en-aut-mei=Satoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuriyamaChiaki en-aut-sei=Kuriyama en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakataShujiro en-aut-sei=Sakata en-aut-mei=Shujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakatoHikari en-aut-sei=Nakato en-aut-mei=Hikari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MishimaSakurako en-aut-sei=Mishima en-aut-mei=Sakurako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhiraAkiko en-aut-sei=Ohira en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=maternal body composition kn-keyword=maternal body composition en-keyword=newborn birth weight kn-keyword=newborn birth weight en-keyword=pre-pregnancy body mass index kn-keyword=pre-pregnancy body mass index en-keyword=fat-free mass kn-keyword=fat-free mass en-keyword=fat mass gain kn-keyword=fat mass gain 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=20260401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Triangulation in teaching probability: teaching materials for the theoretical foundations of probability in real-world applications en-subtitle= kn-subtitle= en-abstract= kn-abstract=This paper proposes using the concept of triangulation with probabilistic models as a means to enhance theoretical inversion for deepening studentsf understanding of the nature of probability in real-world contexts. Triangulation refers to the combined application of multiple methodologies to investigate the same phenomenon, particularly in the social sciences. Theoretical inversion refers to a shift in focus from surprising outcomes to the theoretical foundations of probability. The paper introduces three types of problem-solving tasks designed to enhance one of four types of triangulations: theory triangulation. Theoretical inversion is expected to emerge through engaging in these tasks. The characteristics of the problems are as follows. Problem 1 promotes students to compare different probabilistic models of events under similar procedures. Problem 2 provides students with an opportunity to simplify an experiment by omitting steps that add no new information. Problem 3 enhances studentsf ability to recognise how subtle differences in the experimental setup can affect the resulting probability. These tasks are designed to encourage students to view probabilistic reasoning as a form of modelling and to appreciate the importance of assumptions, definitions of elementary events, and clarity in procedural descriptions. en-copyright= kn-copyright= en-aut-name=UegataniYusuke en-aut-sei=Uegatani en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshibashiIppo en-aut-sei=Ishibashi en-aut-mei=Ippo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakotaAya en-aut-sei=Sakota en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Hiroshima University High School kn-affil= affil-num=2 en-affil=Faculty of Education, Okayama University kn-affil= affil-num=3 en-affil=Hiroshima University High School kn-affil= en-keyword=Probability kn-keyword=Probability en-keyword=triangulation kn-keyword=triangulation en-keyword=mathematical modelling kn-keyword=mathematical modelling en-keyword=theoretical inversion kn-keyword=theoretical inversion END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=5 article-no= start-page=2308 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=Aerobic Exercise Attenuates Epidermal Hyperplasia in an Obesity-Associated Psoriasiform Dermatitis Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Obesity is an important risk factor for psoriasis, and clinical studies indicate that exercise interventions can improve disease severity. However, the mechanisms by which exercise influences psoriatic pathogenesis remain insufficiently understood. To investigate the effects of aerobic exercise on obesity-associated psoriasis, wild-type mice were fed a high-fat diet (HFD) for 7 weeks to induce obesity and subsequently underwent moderate-intensity treadmill running for 3 weeks. Psoriasiform dermatitis was induced by daily topical application of imiquimod (IMQ) to the skin for five consecutive days. HFD increased body weight, epididymal fat mass, and serum cholesterol. HFD-fed mice developed more severe IMQ-induced psoriatic skin changes compared with normal diet-fed mice. Treadmill exercise modestly reduced body weight gain and attenuated epidermal hyperplasia in HFD-fed mice. In contrast, inflammatory cytokine expression, including Tnfa, Il17a, and Il23a, showed modest increases in the skin of HFD-fed exercised mice, which did not parallel the improvement in epidermal hyperplasia. Overall, these findings indicate that while obesity exacerbates psoriasiform dermatitis, aerobic exercise ameliorates epidermal hyperplasia in obese mice without corresponding changes in inflammatory cytokine expression in the skin, suggesting that exercise may influence psoriatic skin changes through multiple metabolic and immunological pathways. en-copyright= kn-copyright= en-aut-name=MatsudaYoshihiro en-aut-sei=Matsuda en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakezakiDaiki en-aut-sei=Takezaki en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoYuma en-aut-sei=Sakamoto en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BabaNobuyasu en-aut-sei=Baba en-aut-mei=Nobuyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IsekiMasanori en-aut-sei=Iseki en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawakamiYoshio en-aut-sei=Kawakami en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShiomiTatsushi en-aut-sei=Shiomi en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MukaiTomoyuki en-aut-sei=Mukai en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology, Kawasaki Medical School kn-affil= affil-num=9 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= en-keyword=psoriasis kn-keyword=psoriasis en-keyword=obesity kn-keyword=obesity en-keyword=aerobic exercise kn-keyword=aerobic exercise en-keyword=imiquimod kn-keyword=imiquimod en-keyword=high-fat diet kn-keyword=high-fat diet END start-ver=1.4 cd-journal=joma no-vol=49 cd-vols= no-issue=2 article-no= start-page=364 end-page=370 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260221 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Functional Transport Properties of Human Zinc Transporter 1: Kinetics and pH-Dependency en-subtitle= kn-subtitle= en-abstract= kn-abstract=Intracellular zinc (Zn2+) homeostasis is essential for physiological and pathological processes and is strictly regulated by Zn2+ transporters. Zinc transporter 1 (ZnT1) is a ubiquitously expressed plasma membrane-localized Zn transporter that exports Zn2+ from the cytoplasm to the extracellular space. However, the functional transport properties regarding kinetics and driving forces of ZnT1 remain debatable. In this study, we established a cell-free proteoliposome assay system and demonstrated that ZnT1 transports Zn2+ with high affinity in pH-dependent and pH-independent manners. The Km and Vmax of pH-dependent Zn2+ transport were 0.40 M and 15.13 nmol/min/mg protein, and those of pH-independent Zn2+ transport were 0.52 M and 8.88 nmol/min/mg protein (low concentrations of Zn2+), 3.02 M and 17.59 nmol/min/mg protein (high concentrations of Zn2+), respectively, suggesting biphasic kinetic components of Zn2+ transport. Even without pH gradient formation, ZnT1 exhibits potent Zn2+ transport activity. In pH dependency, Zn2+ transport activity was higher at an inside pH of 6.0 than at 6.5?7.5 for proteoliposomes, despite the same pH of 0.5?1.5. The Zn2+ transport activity decreased at an outside pH of 8.0, despite an increase in pH. Although previous studies have proposed that ZnT1-mediated Zn2+ transport activity is driven by a calcium (Ca2+) gradient and not by a pH gradient, Ca2+ does not enhance Zn2+ transport activity in the presence or absence of a pH gradient. These results strongly suggest that ZnT1 protein transports Zn2+ optimally at a specific pH and exports excess intracellular Zn2+ even without pH. en-copyright= kn-copyright= en-aut-name=YoshiokaYuma en-aut-sei=Yoshioka en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= affil-num=1 en-affil=Department of Molecular Membrane Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Molecular Membrane Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=zinc transporter 1 kn-keyword=zinc transporter 1 en-keyword=SLC30A1 kn-keyword=SLC30A1 en-keyword=zinc kn-keyword=zinc en-keyword=pH kn-keyword=pH en-keyword=proteoliposome kn-keyword=proteoliposome END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=10464 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Liquid?liquid phase separation by caged coacervating peptides en-subtitle= kn-subtitle= en-abstract= kn-abstract=Liquid?liquid phase separation is an important biomolecular process in the formation of membraneless intracellular organelles that has inspired the development of artificial droplet systems. We developed caged coacervating peptides (CCPs) based on a histidine-rich squid beak protein sequence. The peptides were caged with a photodeprotectable (7-diethylaminocoumarin-4-yl)methoxycarbonyl group. The CCPs formed coacervates in the caged state and were partially dispersed upon blue-light irradiation. Photo-uncaging occurred rapidly, inducing coacervate dispersion. A mutant CCP with reduced ? interactions exhibited efficient photo-dependent disassembly and enabled the encapsulation and release of a fluorescently labeled adenosine 5-triphosphate (Bodipy-ATP) upon irradiation. These CCPs offer an efficient light-controlled approach for biomolecular encapsulation within coacervates and targeted drug delivery. en-copyright= kn-copyright= en-aut-name=BandoAkinari en-aut-sei=Bando en-aut-mei=Akinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KanazakiYuuki en-aut-sei=Kanazaki en-aut-mei=Yuuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TojoRika en-aut-sei=Tojo en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeKazunori en-aut-sei=Watanabe en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry, Kindai University kn-affil= affil-num=3 en-affil=Department of Applied Chemistry, Kindai University 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 Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=Caged coacervating peptide kn-keyword=Caged coacervating peptide en-keyword=Liquid?liquid phase separation kn-keyword=Liquid?liquid phase separation en-keyword=Light kn-keyword=Light END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=558 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=Evaluation of contact-active antibacterial properties of cetylpyridinium chloride?graphene oxide coatings on dental restorative and titanium surfaces: an in vitro study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective Biofilm formation on dental restorative materials and implant surfaces plays a central role in the development of dental caries, periodontal disease, and peri-implantitis. Durable antimicrobial surface treatments that inhibit bacterial adhesion and biofilm formation remain a significant unmet need in restorative and implant dentistry. Therefore, this study aimed to develop a composite coating combining cetylpyridinium chloride and graphene oxide, and to evaluate its durable antibacterial surface modification under in vitro conditions.
Methods A composite coating consisting of cetylpyridinium chloride and graphene oxide was prepared and applied to composite resin and titanium surfaces. Antibacterial activity against Streptococcus mutans and Porphyromonas gingivalis was evaluated using adenosine triphosphate assays and fluorescence-based live/dead staining. Coating retention after washing and air-drying was assessed by optical microscopy and Raman spectroscopy.
Results Cetylpyridinium chloride-graphene oxide-coated surfaces showed a significant reduction in bacterial viability compared with phosphate-buffered saline, ethanol, and cetylpyridinium chloride-only controls. Antibacterial effects were maintained after rinsing and air-drying on both composite resin and titanium surfaces. Raman spectroscopy confirmed the persistence of characteristic graphene oxide bands after washing, indicating stable retention of the coating on the material surfaces.
Conclusions Cetylpyridinium chloride?graphene oxide coatings demonstrate sustained surface-associated antibacterial activity against key cariogenic and periodontal pathogens and remain stably adhered to common dental restorative and implant materials after washing. These findings suggest that cetylpyridinium chloride?graphene oxide coatings may serve as a durable contact-active surface modification strategy to reduce biofilm formation associated with dental caries and peri-implantitis. en-copyright= kn-copyright= en-aut-name=OkuboKeisuke en-aut-sei=Okubo en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanoGen en-aut-sei=Kano en-aut-mei=Gen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KomodaMasato en-aut-sei=Komoda en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KamataHideyuki en-aut-sei=Kamata en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=9 ORCID= affil-num=1 en-affil=Department of Periodontics and Endodontics, Field of Medical Development, 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=Research Institute for Interdisciplinary Science, 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 Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=9 en-affil=Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Wash-resistant antibacterial coating kn-keyword=Wash-resistant antibacterial coating en-keyword=Graphene oxide kn-keyword=Graphene oxide en-keyword=Cetylpyridinium chloride kn-keyword=Cetylpyridinium chloride en-keyword=Oral pathogenic bacteria kn-keyword=Oral pathogenic bacteria 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 (M) in the presence of receptor activator of nuclear factor-B 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/M 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/M 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/M unit kn-keyword=OC/M unit END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=4 article-no= start-page=760 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Role of Nitrate-Reducing Bacteria Isolated from Helicobacter pylori-Infected Individuals in Gastric Cancer Development en-subtitle= kn-subtitle= en-abstract= kn-abstract=Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric mucosa, with a global prevalence in humans of approximately 40%. It is likely the cause of 90% of gastric cancer (GC) cases and thus considered the most prominent driver of GC development. However, during gastric mucosal atrophy, other bacteria such as nitrate-reducing bacteria (NRB) also proliferate. In this study, we isolated NRB from patients with gastritis and GC to examine their effects on the epithelial cell cycle and production of various cytokines in monocytic cell lines. Bacterial counts (excluding H. pylori and NRB) increased with the progression of gastric mucosal atrophy and were significantly higher in patients with GC. Gastric epithelial cell lines were stimulated with isolated NRB, and the proportion of cells in each cell cycle was measured. Strains from patients with open-type gastritis progressed more rapidly through cell cycles than those from patients with GC. NRB isolated from gastric cancer had high nitrate-reducing activity. Thus, NRB may contribute to GC progression during H. pylori-induced carcinogenesis. Therefore, evaluating gastric atrophy and microbiota may be important for managing the risk of GC. en-copyright= kn-copyright= en-aut-name=KuwagiSerika en-aut-sei=Kuwagi en-aut-mei=Serika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KomatsubaraMarina en-aut-sei=Komatsubara en-aut-mei=Marina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=OkanoueShyoutarou en-aut-sei=Okanoue en-aut-mei=Shyoutarou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=WatanabeAkari en-aut-sei=Watanabe en-aut-mei=Akari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YokotaKenji en-aut-sei=Yokota en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Bacteriology, Academic Field of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Bacteriology, Academic Field of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Bacteriology, Academic Field of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Bacteriology, Academic Field of Health Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Academic Field of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Himeji Red Cross Hospital kn-affil= affil-num=7 en-affil=Department of Bacteriology, Academic Field of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Health Care and Rehabilitation, Institute of Biomedical Sciences, Graduate School, Tokushima University kn-affil= affil-num=9 en-affil=Department of Bacteriology, Academic Field of Health Sciences, Okayama University kn-affil= en-keyword=Helicobacter pylori infection kn-keyword=Helicobacter pylori infection en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=nitrate-reducing bacteria kn-keyword=nitrate-reducing bacteria en-keyword=gastritis kn-keyword=gastritis 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=20260318 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Suppression of salt-enhanced apoplastic flow by salicylic acid in rice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Salinity enhances apoplastic flow, resulting in an increment of Na+ uptake and a lower K+/Na+ ratio. Salicylic acid (SA) plays an important role in improving salinity tolerance in plants. The effect of exogenous SA on apoplastic flow in salt-treated rice seedlings was studied using an apoplastic tracer, 8-hydroxy-1,3,6-pyrenetrisulphonic acid (PTS) in light. Application of NaCl at 25 mM to the hydroponic solution significantly increased PTS uptake, while 25 mM NaCl did not affect seedling growth. Application of 25 mM NaNO3 increased PTS uptake to the same degree. Salinity significantly increased sodium (Na+) content but had no significant effect on potassium (K+) content, resulting in a lower K+/Na+ ratio. The application of SA at 0.05 mM and 0.1 mM to the hydroponic solution reduced Na-enhanced PTS uptake. Salicylic acid at 0.05 mM and 0.1 mM significantly reduced Na+ content and slightly increased K+ content in the shoots of rice seedlings, resulting in a higher K+/Na+ ratio. However, SA at up to 0.1 mM did not increase SA contents in shoots under salt stress. These results suggest that exogenous SA reduces Na+ uptake by suppressing Na+-enhanced apoplastic flow in rice seedlings. These findings provide insight into modulation of Na+ transport pathways from roots to shoots by SA and may allow us to utilize brackish water for rice cultivation and to improve salt-tolerant rice through suppression of salt-enhanced apoplastic flow by chemicals such as salicylic acid. en-copyright= kn-copyright= en-aut-name=GalibMd. Asadulla Al en-aut-sei=Galib en-aut-mei=Md. Asadulla Al kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZhaoMaoxiang en-aut-sei=Zhao en-aut-mei=Maoxiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraToshiyuki en-aut-sei=Nakamura en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=HiraiYoshihiko en-aut-sei=Hirai en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakashimaYoshitaka en-aut-sei=Nakashima en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MunemasaShintaro en-aut-sei=Munemasa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MoriIzumi C. en-aut-sei=Mori en-aut-mei=Izumi C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MurataYoshiyuki en-aut-sei=Murata en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=8 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=Apoplastic flow kn-keyword=Apoplastic flow en-keyword=Salicylic acid kn-keyword=Salicylic acid en-keyword=Rice kn-keyword=Rice en-keyword=Salinity kn-keyword=Salinity en-keyword=Trisodium-8-hydroxy-1,3,6-pyrenetrisulphonic acid kn-keyword=Trisodium-8-hydroxy-1,3,6-pyrenetrisulphonic acid END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=1 article-no= start-page=265 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Stability and distribution of dense hydrous magnesium silicates in the mantle transition zone under low water activity conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Water plays a central role in controlling the physical and chemical properties of Earthfs deep interior. It remains uncertain how water is stored in subducting slabs within the mantle transition zone, between depths of about 410 and 660 kilometers, and whether dense hydrous magnesium silicates act as major water carriers to greater depths. Here we report high-pressure and high-temperature laboratory experiments on the Mg-Si-H system at pressures of 16 and 21.5?GPa and a temperature of 1400?K to evaluate hydrous phase stability under transition zone conditions. We find that when bulk water content is below 1.22?wt%, H2O is predominantly incorporated into wadsleyite and ringwoodite rather than forming dense hydrous magnesium silicates. Because estimated water contents in subducted oceanic slabs are typically lower than one weight percent, formation of these silicates is unlikely, suggesting that the mantle transition zone may restrict large scale water transport into the lower mantle. en-copyright= kn-copyright= en-aut-name=SongYunke en-aut-sei=Song en-aut-mei=Yunke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GuoXinzhuan en-aut-sei=Guo en-aut-mei=Xinzhuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZhaiKuan en-aut-sei=Zhai en-aut-mei=Kuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GuoWei en-aut-sei=Guo en-aut-mei=Wei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= affil-num=1 en-affil=Key Laboratory of High-temperature and High-pressure Study of the Earthfs Interior, Institute of Geochemistry, Chinese Academy of Sciences kn-affil= affil-num=2 en-affil=State Key Laboratory of Critical Mineral Research and Exploration, Institute of Geochemistry, Chinese Academy of Sciences kn-affil= affil-num=3 en-affil=Key Laboratory of High-temperature and High-pressure Study of the Earthfs Interior, Institute of Geochemistry, Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=State Key Laboratory of Geomicrobiology and Environmental Changes, School of Earth Sciences, China University of Geosciences (Wuhan) kn-affil= affil-num=5 en-affil=Institute for Planetary Materials, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=171 cd-vols= no-issue=2 article-no= start-page=xaag004 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=Rho kinase and RND3 regulate the direct effect of estradiol-17 on oviductal tonus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ensuring the timely transport of gametes and embryos within the oviduct is essential for the successful establishment of pregnancy. This study investigated the direct effect of estradiol-17 (E2) on bovine oviductal contractility and the differences in responsiveness to E2 during the estrous cycle. Bovine isthmic tissues from four estrous stages were analyzed using the Magnus method to assess contractile responses to E2 and related reagents. Protein expression of G-protein-coupled estrogen receptor 1 (GPER1) and components of the RhoA/Rho kinase (ROCK) signaling pathway were also evaluated. E2 and a GPER1 agonist significantly increased oviductal tonus at 1?4?days after ovulation. This effect was significantly suppressed by treatment with a GPER1 antagonist and a ROCK inhibitor. At 1?4?days after ovulation, both ROCK II expression and ROCK activity were elevated. E2 also enhanced phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and myosin light chain (MLC), key downstream targets of ROCK. Before ovulation, when endogenous E2 levels peak, the expression of RND3?a ROCK inhibitor?was upregulated. The application of an RND inhibitor restored E2 responsiveness in oviductal tonus, ROCK activity, and the phosphorylation of MYPT1 and MLC in oviductal tissues before ovulation. These findings suggest that E2 directly increases oviductal tonus via GPER1 and ROCK/MYPT1/MLC activation at 1?4?days after ovulation. Differences in oviductal responsiveness to E2 during the estrous cycle appear to be mediated by the expression of ROCK and RND3. This mechanism can enable sperm transport within the oviduct at an appropriate time. en-copyright= kn-copyright= en-aut-name=KubotaSayaka en-aut-sei=Kubota en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkawaraRisa en-aut-sei=Okawara en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawanoKohei en-aut-sei=Kawano en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= affil-num=1 en-affil=Laboratory of Reproductive Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=School of Agriculture, Okayama University kn-affil= affil-num=3 en-affil=Laboratory of Reproductive Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Laboratory of Reproductive Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=estradiol-17 kn-keyword=estradiol-17 en-keyword=oviduct kn-keyword=oviduct en-keyword=rho kinase kn-keyword=rho kinase en-keyword=RND3 kn-keyword=RND3 END start-ver=1.4 cd-journal=joma no-vol=135 cd-vols= no-issue= article-no= start-page=103134 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Regulation of brain-specific kinases 1 and 2 (BRSK1/2) by Ca2+/calmodulin en-subtitle= kn-subtitle= en-abstract= kn-abstract=We conducted a genome-wide calmodulin (CaM) interaction screening of 462 GST-fused human protein kinases to identify novel CaM-dependent protein kinases (CaMKs). In addition to known CaMKs, including myosin light chain kinases, CaMK2, and death-associated kinase 2, we identified the brain-specific protein kinase 2 (BRSK2, also known as SAD-A) as a novel CaM interactant. Proximity biotinylation and CaM?sepharose chromatography assays revealed that rat BRSK isoforms (BRSK1/2) interact with CaM in a Ca2+-dependent manner in vitro. We found that CaM suppresses the activation-loop phosphorylation of BRSK1 (at Thr189) and BRSK2 (at Thr175) by liver kinase B1 (LKB1), an activating kinase, in a Ca2+-dependent manner (IC50 of ?7 ?M), thereby inhibiting BRSK activation. LKB1-catalyzed phosphorylation of the catalytic domain mutant of BRSK1 (residues 1?294) at Thr189 was suppressed by the addition of Ca2+/CaM, consistent with direct CaM binding of the kinase domain, as well as wild-type BRSK1. We confirmed that the LKB1 activity was not directly suppressed by Ca2+/CaM, supporting the hypothesis that the direct interaction of Ca2+/CaM with the kinase domain blocks the phosphorylation/activation of BRSK1/2 by LKB1. The kinase activity and PP2C-catalyzed dephosphorylation of LKB1-phosphorylated BRSK1 were not altered by Ca2+/CaM, although it was demonstrated to bind to Ca2+/CaM like that of unphosphorylated BRSK1. This unrecognized mechanism of BRSK1/2 regulation, involving the direct role of Ca2+/CaM binding, which inhibits phosphorylation/activation by LKB1, may open a new Ca2+ signal transduction pathway in neurons. en-copyright= kn-copyright= en-aut-name=WashidaNaoyuki en-aut-sei=Washida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KataokaMoe en-aut-sei=Kataoka en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BrunAnna R. en-aut-sei=Brun en-aut-mei=Anna R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakezakiUryu en-aut-sei=Takezaki en-aut-mei=Uryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HijikawaKo en-aut-sei=Hijikawa en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamauchiHaruki en-aut-sei=Yamauchi en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhtsukaSatomi en-aut-sei=Ohtsuka en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MagariMasaki en-aut-sei=Magari en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorishitaRyo en-aut-sei=Morishita en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TokumitsuHiroshi en-aut-sei=Tokumitsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=3 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=6 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=9 en-affil=CellFree Sciences Co., Ltd. kn-affil= affil-num=10 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=BRSK1 kn-keyword=BRSK1 en-keyword=BRSK2 kn-keyword=BRSK2 en-keyword=calmodulin kn-keyword=calmodulin en-keyword=LKB1 kn-keyword=LKB1 en-keyword=phosphorylation kn-keyword=phosphorylation en-keyword=Ca2+ kn-keyword=Ca2+ en-keyword=CaM-dependent protein kinase kn-keyword=CaM-dependent protein kinase END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=1 article-no= start-page=269 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251125 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=From localized 4f electrons to anisotropic exchange interactions in ferromagnetic CeRh6Ge4 en-subtitle= kn-subtitle= en-abstract= kn-abstract=CeRh6Ge4 is a cerium-based ferromagnetic material exhibiting a quantum critical behavior under pressure. We derive effective exchange interactions, using the framework of density functional theory combined with dynamical mean-field theory. Our results reveal that the nearest-neighbor ferromagnetic interaction along the c axis is isotropic in spin space, leading to a formation of spin chains. On the other hand, the inter-chain coupling is highly anisotropic: The in-plane moment weakly interacts ferromagnetically in the a?b plane to stabilize the ferromagnetic state, whereas the z-component couples antiferromagnetically, contributing to its destabilization. The magnetic anisotropy of the interchain interactions as well as of the local 4f wavefunctions characterizes the magnetic properties underlying the ferromagnetic transition and the quantum critical behavior in CeRh6Ge4. en-copyright= kn-copyright= en-aut-name=ItokazuShoichiro en-aut-sei=Itokazu en-aut-mei=Shoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KirikoshiAkimitsu en-aut-sei=Kirikoshi en-aut-mei=Akimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JeschkeHarald O. en-aut-sei=Jeschke en-aut-mei=Harald O. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtsukiJunya en-aut-sei=Otsuki en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Physics, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3-4 article-no= start-page=656 end-page=588 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260318 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Le contrat social dans la D?claration des droits de lfhomme et du citoyen de 1789 kn-title=1789NtXl錾ƎЉ_ en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HatanoS. en-aut-sei=Hatano en-aut-mei=S. kn-aut-name=gq kn-aut-sei=g kn-aut-mei=q aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Rw_ END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3-4 article-no= start-page=726 end-page=707 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260318 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A Study on the Consequences of Invalid Election Results under Article 251 of the Public Offices Election Act kn-title=EI@251iIl{l̑Iƍ߁jɂ铖ǏʂɊւl@ \ ŎOߘaTN1212W77X2229ł_@Ƃā\ en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=FukushigeS. en-aut-sei=Fukushige en-aut-mei=S. kn-aut-name=dƎq kn-aut-sei=d kn-aut-mei=Ǝq aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Rwwp@ЉȊww END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=237 end-page=251 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260328 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Preliminary Consideration on the Introduction of Philosophical Thinking into Special Needs Education: A Methodological Framework Based on the Concepts of Duration, Becoming, and Diffraction kn-title=ʎxւ̓NwIvlɂ‚Ă̗\Il@ EωE܂̍lɊÂ@Igg݂̎ en-subtitle= kn-subtitle= en-abstract=This paper presents a theoretical and methodological examination aimed at introducing philosophical thinking into the practice of special needs education in response to contemporary challenges in the field. As its theoretical foundation, the study outlines Bergsonf s theory of memory, Deleuze and Guattarif s philosophy of becoming, Baradf s diffractive methodology, and Blomf s diffractive ethnography. Building upon these theories, it proposes a methodological framework that adopts three interrelated analytical perspectives?gmaterial-discursive practices,h gduration,h and gbecomingh?for reading and interpreting educational practices. These perspectives, situated within the paradigm of post-qualitative research, make it possible to understand educational events as relational and processual phenomena rather than fixed outcomes. Future issues include the theoretical integration of the three lenses, clarification of the distinctions between diffractive methodology and diffractive ethnography, and refinement of analytical methods for connecting multiple practice episodes. kn-abstract=@{éC̓ʎx̉ۑ肩CʎxHɓNwIvl𓱓邽߂̗_IE@IŝłB܂C_ՂƂāCxN\́uL_vChD[YK^́uὠNwvCBarad́uܓI@_vCBloḿuܓIGXmOtB[vɂ‚ĊTBāC_Ղɕ@Igg݂ƂāCu|IHvCuvCuωv̎O‚̎_Hǂ݉߂̑ݕ⊮Iȕ͎_Ƃč̗p邱ƂĂB̎_́C|XgIƂāCo֌WIEߒIɑ邱Ƃ”\ɂ̂łB̉ۑƂāCO‚̃YԂ̗_ICܓI@_ƉܓIGXmOtB[̍ىCѕ̎HGs\[hڑĕ`߂͎̕@̐kꂽB en-copyright= kn-copyright= en-aut-name=HAMADAYo en-aut-sei=HAMADA en-aut-mei=Yo kn-aut-name=Mcj kn-aut-sei=Mc kn-aut-mei=j aut-affil-num=1 ORCID= en-aut-name=TAKANOMiyuki en-aut-sei=TAKANO en-aut-mei=Miyuki kn-aut-name=RI kn-aut-sei= kn-aut-mei=RI aut-affil-num=2 ORCID= en-aut-name=SATOSatoru en-aut-sei=SATO en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Okayama Prefectural Okayama Seto Special Needs School kn-affil=RRˍxwZ affil-num=2 en-affil=Hyogo University of Teacher Education kn-affil=ɋww@ affil-num=3 en-affil=Faculty of Education, Okayama University kn-affil=Rwwp@w en-keyword=ʎx (special needs education) kn-keyword=ʎx (special needs education) en-keyword=Nw (philosophy) kn-keyword=Nw (philosophy) en-keyword=͎_ (analytical perspectives) kn-keyword=͎_ (analytical perspectives) en-keyword=|Xgq[}jY (posthumanism) kn-keyword=|Xgq[}jY (posthumanism) en-keyword=I (qualitative research) kn-keyword=I (qualitative research) END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=123 end-page=137 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260328 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A Study on the Involvement of Community Wind Bands in the Community Development of Wind Band Activities; Can Community Wind Bands Serve as Key Supporters in Community Development of Club Activities? kn-title=ty̒nWJɂstyc̊ւɊւ錤 \styc͒nWJ̒SɂȂ蓾邩\ en-subtitle= kn-subtitle= en-abstract=In the community development of wind band activities, the shortage of instructors and rehearsal spaces has become an urgent issue. This study investigates whether community wind bands can serve as key supporters of community development of childrenf s wind band activities progresses. Based on interviews with 20 community wind bands in Okayama Prefecture and text mining analysis, the study revealed differences in their awareness toward community development of club activities. More proactive bands tended to view providing musical instruction to children and engaging in joint activities positively. On the other hand, concerns about instructional skills, time constraints, and the burden of responsibility were identified as potential obstacles. Furthermore, the findings suggest that utilizing public school facilities could help address the issues of rehearsal space and financial constraints faced by community wind bands. However, disparities among municipalities were also found in the actual implementation of public school facility use systems. kn-abstract=@ty̒nWJiȉAnWJjɂāAw҂⊈ꏊ̕s͋iق̉ۑłB{́AnWJiޒŁAstycn̎qǂB̐tyxSƂȂ蓾邩𒲍EBR̎styc20 ĉւ̕蒲ƃeLXg}CjO͂̌ʁAnWJւ̈ӎɂ͍݂AϋɓIȒĉł͎qǂB̉tw⍇ł̊mIɑXmFꂽBŁAwZp⎞ԓIAӔCSւ̕sǂƂȂÔ\ꂽB܂Astyc銈ꏊIȉۑɑ΂ČwZ{݂̊p̉Ɋ^”\ꂽBŁAwZ̎{݊Jɂ‚ẮAۂ̐x^pɂĎ̊Ԃ̊i݂邱Ƃ炩ƂȂB en-copyright= kn-copyright= en-aut-name=MAKINOKunihiko en-aut-sei=MAKINO en-aut-mei=Kunihiko kn-aut-name=ꠖMF kn-aut-sei=ꠖ kn-aut-mei=MF aut-affil-num=1 ORCID= affil-num=1 en-affil=Center for Teacher Education and DevelopmentAOkayama University kn-affil=Rwwp@w 琄i@\tJZ^[ en-keyword=nWJ (community development of club activities) kn-keyword=nWJ (community development of club activities) en-keyword=styc (community wind band) kn-keyword=styc (community wind band) en-keyword=nNu (regional club activities) kn-keyword=nNu (regional club activities) en-keyword=wZ{݊J (community use of school facilities) kn-keyword=wZ{݊J (community use of school facilities) END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=31 end-page=44 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260328 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Analysis of Factors Contributing to Confusion Regarding Left-Right Understanding of Convex Lens Images ?Proposals for Inquiry-Based Learning Based on Textbook Analysis and Teacher Questionnaire? kn-title=ʃY̑̍EɊւ鍬̗v ȏ͂ƋAP[gɂTIȊwтւ̒ en-subtitle= kn-subtitle= en-abstract=This study focused on the confusion students experience regarding the orientation of images during the learning of convex lens in junior high school. It examined the causes of this confusion, identifying insufficient awareness of experimental conditions such as the light source, screen, and observation location. To investigate, the study analyzed changes in the Course of Study for Lower Secondary Schools and textbooks and conducted a questionnaire survey of science teachers. The results revealed that while textbook descriptions have shifted toward specifying the observation location, teaching methods among teachers vary, causing confusion of students. To address these issues, a 3D-printed teaching material was developed that naturally fixes the observation viewpoint. Its effectiveness was examined through teacher training. This material was found to be effective in promoting students' intuitive understanding and bringing inquiry-based learning. kn-abstract=@{́AwZȂ̓ʃYwKŐǩɕɒڂB̗vAEXN[Eώ@ꏊƂ\ɈӎĂȂ_ɂƍl@AwKwv̂Ƌȏ̕ϑJ́AьEւ̃AP[g{B̌ʁAȏ̋Lq͊ώ@ꏊw肷֕ωĂ̂́Aꋳ̎w@ɂ͂΂‚Ak̍ƂȂĂ邱Ƃ𖾂炩ɂB̉ۑ̂߁Aώ@_RɌŒł3D v^ނJACł̗LB{ނ͐k̒I𑣂ATIȊwтoŗLł邱ƂꂽB en-copyright= kn-copyright= en-aut-name=TANIMOTOKunihiko en-aut-sei=TANIMOTO en-aut-mei=Kunihiko kn-aut-name=J{OF kn-aut-sei=J{ kn-aut-mei=OF aut-affil-num=1 ORCID= en-aut-name=INADAYoshihiko en-aut-sei=INADA en-aut-mei=Yoshihiko kn-aut-name=cF kn-aut-sei=c kn-aut-mei=F aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of Education, Okayama University kn-affil=Rwwp@w affil-num=2 en-affil=Faculty of Education, Okayama University kn-affil=Rwwp@w en-keyword=ʃY (Convex lens) kn-keyword=ʃY (Convex lens) en-keyword=㉺Et (the orientation of images) kn-keyword=㉺Et (the orientation of images) en-keyword=ȏ (Textbooks) kn-keyword=ȏ (Textbooks) en-keyword=wKwv (Course of Study) kn-keyword=wKwv (Course of Study) en-keyword=RD v^ (3D printer) kn-keyword=RD v^ (3D printer) 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=20260325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinicopathological and transcriptomic profiles of 101 patients with diffuse large B-cell lymphoma/high-grade B-cell lymphoma with double-hit MYC and BCL2 or BCL6 and triple hit en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims: Diffuse large B-cell lymphoma/high-grade B-cell lymphoma (DLBCL/HGBCL) with MYC and BCL2 rearrangements (double-hit lymphoma with BCL2, DHL-BCL2) is a mature aggressive B-cell lymphoma that also includes concurrent triple hit with BCL6 translocation (TH). DHL with MYC and BCL6 (DH-BCL6) can also occur. The differences among these three DLBCL/HGBCL subtypes have not yet been definitively determined.
Methods and Results: This study characterized the clinicopathological features and transcriptomic profiles of a series of 101 cases of DLBCL/HGBCL that were subclassified according to MYC, BCL2 and BCL6 FISH data, including cell-of-origin (COO)-like, molecular high-grade (MHG)-like and double-hit/dark-zone (DHIT/DZsig)-like signatures. DLBCL/HGBCL-DH-BCL2 was characterized by higher HGBCL morphology, CD10 positivity, GCB Hans's, GCB COO and MHG molecular subtype. DLBCL/HGBCL-TH had higher LDH levels and worse overall survival. DLBCL/HGBCL-DH-BCL6 had higher MUM1 expression, non-GCB Hans', ABC/Unclassified COO, non-MHG and low DHIT/DZ signatures. Transcriptomic analysis showed that DLBCL/HGBCL-DH-BCL2 and DLBCL/HGBCL-TH were close but separated from DLBCL/HGBCL-DH-BCL6. Gene set enrichment analysis (GSEA) revealed different levels of enrichment between the subtypes.
Conclusions: DLBCL/HGBCL-DH-BCL6 differs from the DLBCL/HGBCL-DH-BCL2, and the DLBCL/HGBCL-TH is associated with the worst survival. Analysis of all three genes of MYC, BCL2 and BCL6 is recommended in the context of DLBCL/HGBCL diagnosis. en-copyright= kn-copyright= en-aut-name=MiyaokaMasashi en-aut-sei=Miyaoka en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=CarrerasJoaquim en-aut-sei=Carreras en-aut-mei=Joaquim kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikutiYara Yukie en-aut-sei=Kikuti en-aut-mei=Yara Yukie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IkomaHaruka en-aut-sei=Ikoma en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagaseShunsuke en-aut-sei=Nagase en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoAtsushi en-aut-sei=Ito en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OritaMakoto en-aut-sei=Orita en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawadaHiroshi en-aut-sei=Kawada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakaiRika en-aut-sei=Sakai en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= en-aut-name=TsukasakiKunihiro en-aut-sei=Tsukasaki en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MomoseShuji en-aut-sei=Momose en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KameokaYoshihiro en-aut-sei=Kameoka en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YoshidaMasahiro en-aut-sei=Yoshida en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SatouAkira en-aut-sei=Satou en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KatoSeiichi en-aut-sei=Kato en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OishiNaoki en-aut-sei=Oishi en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SaitoAkio en-aut-sei=Saito en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SadahiraKen en-aut-sei=Sadahira en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MasugiYohei en-aut-sei=Masugi en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 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=22 ORCID= affil-num=1 en-affil=Department of Pathology, School of Medicine, Tokai University kn-affil= affil-num=2 en-affil=Department of Pathology, School of Medicine, Tokai University kn-affil= affil-num=3 en-affil=Department of Pathology, School of Medicine, Tokai University kn-affil= affil-num=4 en-affil=Department of Pathology, School of Medicine, Tokai University kn-affil= affil-num=5 en-affil=Department of Pathology, School of Medicine, Tokai University kn-affil= affil-num=6 en-affil=Department of Pathology, School of Medicine Tokai University Isehara Japan kn-affil= affil-num=7 en-affil=Department of Pathology, School of Medicine, Tokai University kn-affil= affil-num=8 en-affil=Department of Hematology, School of Medicine, Tokai University kn-affil= affil-num=9 en-affil=Department of Medical Oncology, Kanagawa Cancer Center kn-affil= affil-num=10 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=11 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=12 en-affil=Department of Hematology, International Medical Center, Saitama Medical University kn-affil= affil-num=13 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=14 en-affil=Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Hematology, Osaka City General Hospital kn-affil= affil-num=16 en-affil=Department of Surgical Pathology, Aichi Medical University Hospital kn-affil= affil-num=17 en-affil=Center for Clinical Pathology, Fujita Health University Hospital kn-affil= affil-num=18 en-affil=Department of Pathology, University of Yamanashi kn-affil= affil-num=19 en-affil=Department of Hematology, NHO Shibukawa Medical Center kn-affil= affil-num=20 en-affil=Division of Hematology, Kawasaki Municipal Kawasaki Hospital kn-affil= affil-num=21 en-affil=Department of Pathology, School of Medicine, Tokai University kn-affil= affil-num=22 en-affil=Department of Pathology, School of Medicine, Tokai University kn-affil= en-keyword=BCL2 kn-keyword=BCL2 en-keyword=BCL6 kn-keyword=BCL6 en-keyword=high-grade B-cell lymphoma kn-keyword=high-grade B-cell lymphoma en-keyword=molecular profile kn-keyword=molecular profile en-keyword=MYC kn-keyword=MYC en-keyword=rearrangements kn-keyword=rearrangements END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3 article-no= start-page=84 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A real-world comparison of nivolumab plus cabozantinib and pembrolizumab plus lenvatinib focusing on safety outcomes in metastatic renal cell carcinoma: results from the JK-FOOT consortium en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Immune checkpoint inhibitor (ICI)-based combination therapy is a standard first-line treatment for metastatic renal cell carcinoma (mRCC), with combinations such as nivolumab plus cabozantinib (Nivo?+?Cabo) and pembrolizumab plus lenvatinib (Pem?+?Len) demonstrating favorable oncologic outcomes. However, no direct comparisons between these two regimens have been conducted. This study aimed to compare the safety and oncologic outcomes of Nivo?+?Cabo and Pem?+?Len in patients with mRCC.
Methods This retrospective study included 185 patients with mRCC treated with Nivo?+?Cabo (n?=?81) or Pem?+?Len (n?=?104) between January 2018 and June 2025 across multiple institutions. The primary outcome was a comparison of treatment-related adverse events (TrAEs). Oncologic outcomes, including objective response rate (ORR), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS), were compared using one-to-one propensity score matching.
Results Any-grade TrAEs occurred in 90% of patients in the Nivo?+?Cabo group and 92% in the Pem?+?Len group (p?=?0.6). Severe TrAEs (grade???3) were more frequent in the Pem?+?Len group (44%) than in the Nivo?+?Cabo group (30%, p?=?0.048). Tyrosine kinase inhibitor dose reduction and treatment discontinuation rates were similar between groups. In the matched cohort (Nivo?+?Cabo: n?=?74; Pem?+?Len: n?=?74), ORRs were comparable (66% vs. 71%, p?=?0.6). With a median follow-up of 17 months, no significant differences were observed in PFS (p?=?0.4), CSS (p?=?0.9), or OS (p?=?0.5).
Conclusions Nivo?+?Cabo and Pem?+?Len demonstrated similar oncologic efficacy as first-line treatments for mRCC. However, Pem?+?Len was associated with more severe TrAEs. Careful toxicity management and shared decision-making are essential when selecting ICI-based combinations. en-copyright= kn-copyright= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujinoTakuya en-aut-sei=Tsujino en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaenosonoRyoichi en-aut-sei=Maenosono en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyodaShingo en-aut-sei=Toyoda en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NukayaTakuhisa en-aut-sei=Nukaya en-aut-mei=Takuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorinakaHirofumi en-aut-sei=Morinaka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TamuraKeita en-aut-sei=Tamura en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FukuokayaWataru en-aut-sei=Fukuokaya en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UrabeFumihiko en-aut-sei=Urabe en-aut-mei=Fumihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MurakamiMasaya en-aut-sei=Murakami en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakaharaKiyoshi en-aut-sei=Takahara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujitaKazutoshi en-aut-sei=Fujita en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AzumaHaruhito en-aut-sei=Azuma en-aut-mei=Haruhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 ORCID= en-aut-name=InamotoTeruo en-aut-sei=Inamoto en-aut-mei=Teruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KomuraKazumasa en-aut-sei=Komura en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KimuraTakahiro en-aut-sei=Kimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=4 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=5 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=6 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=7 en-affil=Department of Urology, Faculty of Medicine, Kindai University kn-affil= affil-num=8 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= affil-num=9 en-affil=Department of Urology, Kawasaki Medical School kn-affil= affil-num=10 en-affil=Department of Urology, Hamamatsu Medical University kn-affil= affil-num=11 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=13 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=14 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= affil-num=16 en-affil=Department of Urology, Faculty of Medicine, Kindai University kn-affil= affil-num=17 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=18 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Urology, Hamamatsu Medical University kn-affil= affil-num=20 en-affil=Department of Urology, Kawasaki Medical School kn-affil= affil-num=21 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= en-keyword=Metastatic renal cell carcinoma kn-keyword=Metastatic renal cell carcinoma en-keyword=Immune checkpoint inhibitor kn-keyword=Immune checkpoint inhibitor en-keyword=Pembrolizumab kn-keyword=Pembrolizumab en-keyword=Lenvatinib kn-keyword=Lenvatinib en-keyword=Nivolumab kn-keyword=Nivolumab en-keyword=Cabozantinib kn-keyword=Cabozantinib END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=35 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=A case of tubulointerstitial nephritis with infiltration of neutrophils and interleukin-17-positive cells associated with Beh?etfs disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Beh?etfs disease (BD) is a non-infectious inflammatory condition characterized by neutrophilic infiltration. In addition to primary symptoms, including oral and genital ulcers, ocular involvement, and skin lesions, BD can also affect various organs. However, renal involvement, particularly in tubulointerstitial nephritis, has rarely been described. Herein, a rare case of acute tubulointerstitial nephritis in a patient clinically diagnosed with BD is reported. The renal lesion presented with other symptoms of BD and fever, and was considered to be BD-related due to the presence of neutrophilic infiltration and its responsiveness to BD-directed therapy. Alterations in T-helper (Th) 1, Th2, and Th17 cytokine profiles are associated with BD activity. Interleukin (IL)-17 plays a central role in neutrophil activation, and recent studies have demonstrated a strong correlation between IL-17A levels and BD activity. In the present case, elevated serum IL-17A levels and infiltration of IL-17A-positive cells into the renal tissue reflected an active phase of BD and a BD-associated renal lesion. en-copyright= kn-copyright= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaKeiko en-aut-sei=Tanaka en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KubotaNatsuki en-aut-sei=Kubota en-aut-mei=Natsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsuyamaTakayuki en-aut-sei=Katsuyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Tubulointerstitial nephritis kn-keyword=Tubulointerstitial nephritis en-keyword=Beh?etfs disease kn-keyword=Beh?etfs disease en-keyword=Neutrophils kn-keyword=Neutrophils en-keyword=Interleukin-17 kn-keyword=Interleukin-17 en-keyword=T-helper (Th) 1/Th2/Th17 cytokines kn-keyword=T-helper (Th) 1/Th2/Th17 cytokines END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=3 article-no= start-page=580 end-page=589 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Cysteine-Specific Cationization Strategy for Versatile Antibody Production against Intrinsically Disordered Proteins en-subtitle= kn-subtitle= en-abstract= kn-abstract=Several autoantigens relevant to the immune system, especially those targeted by autoantibodies induced by antitumor responses, tend to be rich in disordered regions and are prone to aggregation. This inherent instability presents significant challenges for the production, purification, and analysis of autoantigens in laboratory settings. Cysteine-specific cationization can effectively solubilize and purify these challenging proteins, allowing the isolation of full-length water-soluble antigens in their denatured state. The purified antigens enable accurate multiplex autoantibody assays using a suspension Luminex bead array platform. However, well-validated positive control antibodies are essential to ensuring precise clinical diagnosis. In this study, we prepared and characterized a panel of control antibodies by immunizing rabbits with cysteine-specific S-cationized antigens. The resulting antibodies predominantly recognized linear epitopes and were highly effective as quality control reagents in autoantibody array assays. Additionally, these antibodies maintained their ability to bind to their native, unmodified intracellular counterparts, highlighting the usefulness of this approach for producing antibodies against intrinsically disordered proteins. Although a modest immune response against the S-cationized modification site was observed, it remained minimal and did not affect the usefulness of the antibodies for assay validation. We propose this versatile cysteine-specific cationization platform for managing unstable proteins rich in disordered regions, supporting antigen production for diagnostics, and antibody development for research and validation purposes. en-copyright= kn-copyright= en-aut-name=SakaguchiRyui en-aut-sei=Sakaguchi en-aut-mei=Ryui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyamotoAi en-aut-sei=Miyamoto en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KutsumaRikako en-aut-sei=Kutsuma en-aut-mei=Rikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriTakeru en-aut-sei=Mori en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakashimaDaichi en-aut-sei=Nakashima en-aut-mei=Daichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MasuiMirei en-aut-sei=Masui en-aut-mei=Mirei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=FutamiMidori en-aut-sei=Futami en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoriiMariko en-aut-sei=Morii en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OshikiToshiyuki en-aut-sei=Oshiki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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 Interdisciplinary Science and Engineering in Health Systems, Okayama 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=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Department of Bioscience, Faculty of Life Science, Okayama University of Science kn-affil= affil-num=9 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=10 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=3 article-no= start-page=e202500639 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=PPy]Coated Wire Actuators for the Micromechanostimulation of Cells: Fabrication and Characterization en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cellular mechanotransduction signals play a crucial role in physiological and pathological conditions, including skeletal disorders. Although various systems exist to mechanically stimulate cultured cells, most are constrained by incubator incompatibility, limited physiological relevance, nonuniform stimulation, or complexity. The objective of this article is to develop and validate a compact, incubator-compatible tool capable of delivering localized and physiologically relevant mechanical stimulation to small cell populations. Here, we introduce a polypyrrole-based wire-shaped microactuator designed to induce localized mechanical stress to adjacent cells. These wire-shaped microactuators are biocompatible, easy-to-use, and compact for use within standard in vitro cell culture systems. Using a noncontact optical method, we characterize the actuation of polypyrrole-coated wires in an aqueous NaDBS electrolyte, showing radial expansion of 1.5?8??m depending on the deposited polypyrrole film thickness, comparable to cellular dimensions. Next, the actuation is confirmed to be robust and stable to use in cell culture media at physiological temperature. To evaluate biological relevance, osteoblastic KUSA-A1 cells are mechanically stimulated inside the incubator and transcriptomic changes are assessed. Mechanical stimulation resulted in upregulation of genes previously associated with mechanotransduction, including Fos and Fosb. Additionally, several uncharacterized long noncoding RNAs are differentially expressed, suggesting potential novel players in the mechanotransduction pathway. en-copyright= kn-copyright= en-aut-name=Ortega]SantosAmaia B. en-aut-sei=Ortega]Santos en-aut-mei=Amaia B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayanoSatoru en-aut-sei=Hayano en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaraEmilio Satoshi en-aut-sei=Hara en-aut-mei=Emilio Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Mart?nezJose G. en-aut-sei=Mart?nez en-aut-mei=Jose G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JagerEdwin W. H. en-aut-sei=Jager en-aut-mei=Edwin W. H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Sensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Link?ping University kn-affil= affil-num=2 en-affil=Department of Orthodontics, Okayama University Hospital kn-affil= affil-num=3 en-affil=Advanced Research Center for Oral and Craniofacial Sciences Dental School, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Sensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Link?ping University kn-affil= affil-num=5 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Sensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Link?ping University kn-affil= en-keyword=conducting polymers kn-keyword=conducting polymers en-keyword=mechanotransduction kn-keyword=mechanotransduction en-keyword=osteoblasts kn-keyword=osteoblasts en-keyword=polypyrrole kn-keyword=polypyrrole en-keyword=RNA sequencing kn-keyword=RNA sequencing en-keyword=soft-microactuators kn-keyword=soft-microactuators END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=1 article-no= start-page=bbag021 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=SGCRNA: spectral clustering-guided co-expression network analysis without scale-free constraints for multi-omic data en-subtitle= kn-subtitle= en-abstract= kn-abstract=Weighted gene co-expression network analysis (WGCNA) is among the most widely employed methods in bioinformatics. WGCNA enables the identification of gene clusters (modules) exhibiting correlated expression patterns, the association of these modules with traits, and the exploration of candidate biomarker genes by focusing on hub genes within the modules. WGCNA has been successfully applied in diverse biological contexts. However, conventional algorithms manifest three principal limitations: the assumption of scale-free topology, the requirement for parameter tuning, and the neglect of regression line slopes. These limitations are addressed by SGCRNA. SGCRNA provides Julia functions for the analysis of co-expression networks derived from various types of biological data, such as gene expression data. The Julia packages and their source code are freely available at https://github.com/C37H41N2O6/SGCRNAs.jl. en-copyright= kn-copyright= en-aut-name=OsoneTatsunori en-aut-sei=Osone en-aut-mei=Tatsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakaoTomoka en-aut-sei=Takao en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtakeShigeo en-aut-sei=Otake en-aut-mei=Shigeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakaradaTakeshi en-aut-sei=Takarada en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=co-expression network analysis kn-keyword=co-expression network analysis en-keyword=multi-omics kn-keyword=multi-omics en-keyword=spectral clustering kn-keyword=spectral clustering END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=4 article-no= start-page=80 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=Role-Based Efficient Proactive Secret Sharing with User Revocation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Proactive secret sharing (PSS), an extension of secret-sharing schemes, safeguards sensitive data in dynamic distributed networks by periodically refreshing shares to counter adversarial attacks. In our previous work, we constructed a non-interactive proactive secret scheme by integrating threshold homomorphic encryption (ThHE) while reducing the communication complexity to ?(?). Not only is refreshing shares important but revoking the shares of users who have left the system is also essential in practical dynamic membership scenarios. However, the previous work was insufficient for supporting explicit user revocation. This study strengthens the description of roles for authorized users and proposes a scheme to achieve non-interactive share refresh and dynamic user management. In each epoch, authorized users are classified into three roles: retain, newly join, and rejoin, and they receive a broadcast of the compact ciphertext encoding both the refresh information and the revocation instructions from the trusted center (dealer). Authorized users independently derive new shares through homomorphic computations, whereas revoked users are unable to generate new shares. Hash functions are used to bind revocation parameters to the cryptographic hashes of valid users in order to guarantee integrity during revocation, allowing for effective verification without compromising non-interactivity. Our new scheme not only extends the revocation structure but also preserves the ?(?) communication complexity. en-copyright= kn-copyright= en-aut-name=HeYixuan en-aut-sei=He en-aut-mei=Yixuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KoderaYuta en-aut-sei=Kodera en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NogamiYasuyuki en-aut-sei=Nogami en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HudaSamsul en-aut-sei=Huda en-aut-mei=Samsul 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Interdisciplinary Education and Research Field, Okayama University kn-affil= en-keyword=proactive secret sharing kn-keyword=proactive secret sharing en-keyword=user revocation kn-keyword=user revocation en-keyword=threshold homomorphic encryption kn-keyword=threshold homomorphic encryption en-keyword=non-interactive kn-keyword=non-interactive END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=21 article-no= start-page=6651 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Integrated Authentication Server Design for Efficient Kerberos?Blockchain VANET Authentication en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vehicular Ad Hoc Network (VANET) is a fundamental component of the intelligent transportation systems (ITS), providing critical road information to users. However, the volatility of VANETs creates significant vulnerabilities from malicious actors. Thus, verifying joining entities is crucial to maintaining the VANETfs communication security. Authentication delays must stay below 100 ms to meet VANET requirements, posing a major challenge for security. Our previous research introduced a Kerberos?Blockchain (KBC) authentication system that contains two main components separately: Authentication Server (AS) and Ticket Granting Server (TGS). However, this KBC architecture required an additional server to accommodate increasing vehicle volumes in urban environments, leading to higher infrastructure costs. This paper presents an integrated authentication server that merges AS and TGS into a Combined Server (CBS) while retaining blockchain security. We evaluate it using OMNeT++ with SUMO for traffic simulation and Ganache for blockchain implementation. Results show that CBS removes the need for an extra server while keeping authentication delays under 100 ms. It also improves throughput by 104% and reduces signaling overhead by 45% compared to KBC. By optimizing authentication without compromising security, the integrated server greatly enhances the cost-effectiveness and efficiency of VANET systems. en-copyright= kn-copyright= en-aut-name=RahayuMaya en-aut-sei=Rahayu en-aut-mei=Maya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HossainMd. Biplob en-aut-sei=Hossain en-aut-mei=Md. Biplob kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HudaSamsul en-aut-sei=Huda en-aut-mei=Samsul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NogamiYasuyuki en-aut-sei=Nogami en-aut-mei=Yasuyuki 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Interdisciplinary Education and Research Field, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=VANET security kn-keyword=VANET security en-keyword=blockchain kn-keyword=blockchain en-keyword=integrated authentication server kn-keyword=integrated authentication server en-keyword=Kerberos authentication kn-keyword=Kerberos authentication en-keyword=Vehicular Ad Hoc Network kn-keyword=Vehicular Ad Hoc Network END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=1 article-no= start-page=133 end-page=142 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251016 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Study on Zeek IDS Effectiveness for Cybersecurity in Agricultural IoT Networks en-subtitle= kn-subtitle= en-abstract= kn-abstract=As agriculture moves toward Agriculture 4.0, which uses Internet of Things (IoT) devices to collect data in real time and monitor things from a distance, these networks are becoming increasingly vulnerable to cyberattacks. A common method used to protect against these kinds of threats is the use of intrusion detection systems (IDS). However, the agricultural environment is often changing and has limited resources, which makes cybersecurity challenging. Several available IDS tools are not designed to work properly in places with few resources, intermittent access, and unpredictable network conditions. This paper investigates the performance of Zeek, an open-source IDS, in identifying potential threats in agricultural IoT networks. We performed both offline and real-time experiments: offline analysis used pcap files from the Stratosphere Laboratory dataset, and real-time evaluation involved simulated live attack scenarios, focusing on unauthorized access attempts and distributed denial-of-service (DDoS) attacks. Zeek's performance was assessed based on CPU and memory utilization, as well as quality of service (QoS) metrics. From the experimental results, we found that Zeek was quite effective in protecting agricultural IoT networks against typical threats. Memory usage remained stable around 5% during offline analysis and under 20% during active attacks. However, CPU usage was more volatile, peaking at 120% during DDoS events. In terms of QoS, the system maintained a good throughput (1,375 kbits/s) with minimal packet loss (0.000186%). Among the attack types that we tested, brute force attacks, which represent attempts at unauthorized access, had the strongest effect on network performance, increasing delay to 2.159 ms and jitter to 0.793 ms. It seems clear that a heavier traffic load during such attacks can interfere with QoS. On the basis of our observation, we recommend practical deployment strategies for agricultural IoT systems that take these limitations into consideration, aiming to keep networks both secure and efficient under pressure. en-copyright= kn-copyright= en-aut-name=HudaSamsul en-aut-sei=Huda en-aut-mei=Samsul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MusthafaMuhammad Bisri en-aut-sei=Musthafa en-aut-mei=Muhammad Bisri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShamimS. M. en-aut-sei=Shamim en-aut-mei=S. M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NogamiYasuyuki en-aut-sei=Nogami en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Interdisciplinary Education and Research Field, 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=agricultural IoT kn-keyword=agricultural IoT en-keyword=Zeek IDS kn-keyword=Zeek IDS en-keyword=intrusion detection systems kn-keyword=intrusion detection systems en-keyword=open-source security tools kn-keyword=open-source security tools en-keyword=Agriculture 4.0 kn-keyword=Agriculture 4.0 en-keyword=cybersecurity kn-keyword=cybersecurity en-keyword=Raspberry Pi kn-keyword=Raspberry Pi END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=8840 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260317 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tribolium castaneum with longer duration of tonic immobility have more variations corresponding to the human Parkinsonfs disease genomic region en-subtitle= kn-subtitle= en-abstract= kn-abstract=Parkinsonfs disease (PD) is a common neurodegenerative syndrome characterized by the loss of dopaminergic neurons and is also a progressive neurodegenerative disorder that is characterized by dopamine deficiency. We established strains artificially selected for longer and shorter durations of tonic immobility, an antipredator behavior that has received much attention recently, in the red flour beetle, Tribolium castaneum, a model insect species for molecular analyses different from Drosophila melanogaster. Previous studies have shown that the long strains (L-strain) have significantly lower levels of dopamine expression in the brain than the short strains (S-strain) and that they have an abnormal pattern of locomotor activity. Furthermore, previous studies have shown that administering dopamine to L-strain beetles reduces the duration of tonic immobility. Transcriptome analysis of brain and thorax of the L- and S-strains also showed differences in mRNA expression of genes involved in dopamine synthesis and tyrosine metabolism. These results indicate that the phenotype and molecular basis of the L-strain are similar to those of Parkinsonfs syndrome symptoms. In order to establish a link between T. castaneum and PD, we compared the DNA sequences of the L- and S-strains to human genes affecting dopaminergic pathways. The DNA comparison revealed many mutated regions in these genes in the L-strain. We discuss the relationship between dopaminergic pathway genes and PD-like phenotypes across humans, Drosophila, and the red flour beetle. en-copyright= kn-copyright= en-aut-name=TanakaKeisuke en-aut-sei=Tanaka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SasakiKen en-aut-sei=Sasaki en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YajimaShunsuke en-aut-sei=Yajima en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyatakeTakahisa en-aut-sei=Miyatake en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=NODAI Genome Research Center, Tokyo University of Agriculture kn-affil= affil-num=2 en-affil=Graduate School of Agriculture, Tamagawa University kn-affil= affil-num=3 en-affil=NODAI Genome Research Center, Tokyo University of Agriculture kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=119 cd-vols= no-issue=1 article-no= start-page=9 end-page=17 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=Big data-driven target identification by machine learning: DRD2 as a therapeutic target for psoriasis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The development of medical treatments has traditionally relied on researchers leveraging scientific knowledge to hypothesize disease mechanisms and identify therapeutic agents. However, the depletion of novel therapeutic targets has become a significant challenge, resulting in stagnation within pharmaceutical research.
Objective: To address the scarcity of therapeutic targets, we developed a machine learning (ML)-based system capable of predicting therapeutic target molecules for diseases. To validate its utility, we applied this system to psoriasis, aiming to identify novel treatment strategies.
Methods: Our approach utilized a large clinical database to calculate reporting odds ratios for all drugs associated with the prevention of diseases of interest. We identified target proteins by analyzing large chemical structure databases to discover proteins commonly associated with preventive drug candidates. Experimental validation was conducted by administering a predicted therapeutic candidate in an imiquimod-induced psoriasis mouse model.
Results: The ML-based predictions identified drugs for Parkinsonfs disease as potential preventive candidates for psoriasis. Further analysis highlighted dopamine receptor D2 (DRD2) as a therapeutic target. Administration of a DRD2 agonist alleviated psoriasis symptoms in mice, evidenced by the downregulation of mRNA expression in the IL-17 pathway and reduced serum tumor necrosis factor- levels.
Conclusion: This study demonstrates the utility of a novel ML-based system for identifying therapeutic targets, as shown by its successful application in uncovering the role of DRD2 in psoriasis. Beyond psoriasis, this system offers significant potential for exploring pathological mechanisms and discovering therapeutic targets across various diseases. en-copyright= kn-copyright= en-aut-name=SakaiTakashi en-aut-sei=Sakai en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SawadaRyusuke en-aut-sei=Sawada en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IchinoseOtoha en-aut-sei=Ichinose en-aut-mei=Otoha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TerabayashiTakeshi en-aut-sei=Terabayashi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HatanoYutaka en-aut-sei=Hatano en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamanishiYoshihiro en-aut-sei=Yamanishi en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshizakiToshimasa en-aut-sei=Ishizaki en-aut-mei=Toshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Dermatology, Faculty of Medicine, Oita University kn-affil= affil-num=2 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology kn-affil= affil-num=4 en-affil=Department of Pharmacology, Faculty of Medicine, Oita University kn-affil= affil-num=5 en-affil=Department of Dermatology, Faculty of Medicine, Oita University kn-affil= affil-num=6 en-affil=Department of Complex Systems Science, Graduate School of Informatics, Nagoya University kn-affil= affil-num=7 en-affil=Department of Pharmacology, Faculty of Medicine, Oita University kn-affil= en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=big data kn-keyword=big data en-keyword=machine learning kn-keyword=machine learning en-keyword=dopamine receptor D2 kn-keyword=dopamine receptor D2 en-keyword=psoriasis kn-keyword=psoriasis END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=2 article-no= start-page=110 end-page=118 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trend of adjusted antenatal care visits on pregnant women and neonatal during the COVID-19 pandemic: Findings from a three districts survey in 2021 en-subtitle= kn-subtitle= en-abstract=Upaya pengembangan kesehatan berkelanjutan di tengah wabah penyakit menular seperti COVID-19 memerlukan sistem kesehatan ibu yang tangguh. Dengan kasus yang terus meningkat secara global dan di seluruh Asia, Indonesia menghadapi gangguan signifikan pada layanan esensial. Terdapat kesenjangan penelitian kritis dalam memanfaatkan analisis time-series yang disesuaikan untuk memisahkan dampak pandemi dari variasi musiman di Indonesia perkotaan. Studi ini mengevaluasi tren kunjungan perawatan antenatal (ANC) (Januari 2019?Desember 2020) di tiga Pusat Kesehatan Masyarakat (Puskesmas) di Makassar: Bara-Baraya, Jongaya dan Batua menggunakan analisis Interrupted Time Series (ITS). Temuan menunjukkan penurunan signifikan dalam kunjungan selama kuartal kedua dan ketiga tahun 2020, terutama disebabkan oleh kekhawatiran akan penularan. Kami menyarankan integrasi telemedisin dan kunjungan rumah untuk menjaga kelangsungan perawatan. Meskipun berfokus pada Makassar perkotaan, hasil ini menjadi acuan penting bagi kesehatan dan menawarkan solusi yang dapat diterapkan bagi negara-negara berkembang lain yang menghadapi keterbatasan sumber daya. Studi ini menekankan perlunya strategi pencegahan inklusif untuk melindungi kesehatan ibu di daerah perkotaan dan pedesaan di negara-negara berpendapatan rendah hingga menengah selama krisis kesehatan sistemik. kn-abstract=Sustainable health development efforts amid infectious disease outbreaks such as Coronavirus disease 2019 (COVID-19) require a resilient maternal health system. With cases rising globally and across Asia, Indonesia faces significant disruptions in essential services. A critical research gap exist in utilizing adjusted time-series analysis to isolated pandemic impact from seasonal variation in urban Indonesia. This study evaluates trends in antenatal care (ANC) visits (January 2019?December 2020) at three Community Health Centres in Makassar: Bara-Baraya, Jongaya and Batua using Interrupted Time Series (ITS) analysis. Findings reveal a significant decline in visits during the second and third quarters of 2020, primarily due to transmission fears. We suggest integration of telemedicine and home visits to maintain continuity of care. Although focused on urban Makassar, these results are an important reference for health and offer applicable solutions for other developing countries facing resource constraints. This study emphasizes the need for inclusive prevention strategies to protect maternal health in urban and rural areas in low- to middle-income countries during systemic health crises. en-copyright= kn-copyright= en-aut-name=IbrahimJuliani en-aut-sei=Ibrahim en-aut-mei=Juliani 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=IbrahimSukaeni en-aut-sei=Ibrahim en-aut-mei=Sukaeni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Departement of Public Health, Faculty of Medicine and Health Science, Universitas Muhammadiyah Makassar kn-affil= affil-num=2 en-affil=Nursing of Department, Graduate School of Health Science, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Medicine, Bosowa University kn-affil= en-keyword=antenatal care kn-keyword=antenatal care en-keyword=covid-19 kn-keyword=covid-19 en-keyword=interrupted time series kn-keyword=interrupted time series en-keyword=maternal health kn-keyword=maternal health en-keyword=neonatal birth kn-keyword=neonatal birth END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=6 article-no= start-page=845 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Seasonal Variations in the Risk of Outpatient Acute Kidney Injury in Patients with Chronic Kidney Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Acute kidney injury (AKI) frequently occurs in the outpatient setting and is associated with adverse renal and survival outcomes. However, there is no established definition of outpatient AKI, and the risk factors, especially seasonal variation, remain limited. This study aimed to investigate seasonal variation in the risk of outpatient AKI. Methods: This retrospective observational study used routinely collected clinical laboratory data from a single hospital in Japan between 2007 and 2022. Outpatient AKI was defined as ?35% relative decline in estimated glomerular filtration rate (eGFR) compared with a preceding outpatient measurement obtained within 14?90 days. Monthly and seasonal variations in outpatient AKI risk in patients with chronic kidney disease (CKD) were evaluated using logistic regression models. Subgroup analyses were performed according to AKI stage, age group, and CKD stage. Results: A total of 203,853 outpatient records were analyzed. The incidence of outpatient AKI was highest in August and lowest in November. Analyses demonstrated significantly increased odds ratios of outpatient AKI in January, February, July, and August. Seasonally, the risk was significantly higher during the summer. Stage-specific analyses showed that AKI stage 1 was more frequent in the summer, whereas AKI stage 2 tended to increase during the winter. Conclusions: Outpatient AKI exhibits distinct seasonal patterns, with increased risk during both summer and winter and differential associations according to AKI severity and baseline kidney function. Recognition of these patterns may help identify vulnerable populations and inform targeted preventive strategies for outpatient AKI. en-copyright= kn-copyright= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiSoichiro en-aut-sei=Haraguchi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=acute kidney injury kn-keyword=acute kidney injury en-keyword=chronic kidney disease kn-keyword=chronic kidney disease en-keyword=outpatients kn-keyword=outpatients en-keyword=seasons kn-keyword=seasons 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 Fern?ndez-PachecoPedro Antonio en-aut-sei=de la Rosa Fern?ndez-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=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=32 cd-vols= no-issue=1 article-no= start-page=9 end-page=19 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260331 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Petrological study of Sue ware from the Sabukaze kiln site, Okayama Prefecture kn-title=×qՌQ{b̊ΊwI en-subtitle= kn-subtitle= en-abstract= kn-abstract=@The Sabukaze kiln site, a representative ancient tunnel-kiln site in the Kibi region, worked during the Asuka period (from early 7th century to early 8th century) to produce Sue ware including jars, cups, coffins, and ornamental tiles. To determine the provenance of the materials used for the Sue ware, we carried out petrological analyses of 13 Sue sherds, including optical microscopy, X-ray diffractometry, X-ray fluorescence spectroscopy, Raman spectroscopy, and electron-probe analysis. In spite of the difference of production time, all the Sue sherds show close similarities in modal proportion of mineral inclusions with dominant quartz and feldspar, and minor volcanic glass, in chemical compositions of feldspar and interstitial matrix, and in whole-sherd chemical composition. These similarities suggest that the paste materials of the Sabukaze Sue ware were commonly derived from weathered rhyolitic rocks and obtained from the same or neighboring mining site(s) located near the kiln site. en-copyright= kn-copyright= en-aut-name=ANAMITaiji en-aut-sei=ANAMI en-aut-mei=Taiji kn-aut-name=쑾m kn-aut-sei= kn-aut-mei=m aut-affil-num=1 ORCID= en-aut-name=NOZAKAToshio en-aut-sei=NOZAKA en-aut-mei=Toshio kn-aut-name=rv kn-aut-sei= kn-aut-mei=rv aut-affil-num=2 ORCID= en-aut-name=KIMURAOsamu en-aut-sei=KIMURA en-aut-mei=Osamu kn-aut-name=ؑ kn-aut-sei=ؑ kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Earth Sciences, Okayama University kn-affil=Rww@‹RȊw affil-num=2 en-affil=Department of Earth Sciences, Okayama University kn-affil=Rwwp@‹RȊww affil-num=3 en-affil=Department of Archaeology, Osaka University kn-affil=wlÊw en-keyword=Sabukaze kiln site kn-keyword=Sabukaze kiln site en-keyword=Sue ware kn-keyword=Sue ware en-keyword=provenance kn-keyword=provenance en-keyword=petrology kn-keyword=petrology END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=1 article-no= start-page=1 end-page=7 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260331 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Microtremor exploration in Kojima Bay area, Okayama Plain kn-title=R쎙pݕł̔ACT en-subtitle= kn-subtitle= en-abstract= kn-abstract=@This report describes microtremor array observations conducted at two sites for deep exploration and three sites for shallow exploration around Kojima Bay area in the southern Okayama Plain. Based on these records, the ground velocity structures were estimated. The results yielded solutions indicating the depth of the top of the seismic base layer (equivalent to 3 km/s layer) ranges from 140 to 300 m, while the depth of the top of the engineering basement layer (equivalent to 0.6 km/s layer) is approximately about 13?14 m. The shallow exploration results also suggested the possible presence of an inversion layer. These estimated velocity structure models provided a reasonable explanation for the observed phase velocities. en-copyright= kn-copyright= en-aut-name=YAMADANobuyuki en-aut-sei=YAMADA en-aut-mei=Nobuyuki kn-aut-name=RcLV kn-aut-sei=Rc kn-aut-mei=LV aut-affil-num=1 ORCID= en-aut-name=TAKENAKAHiroshi en-aut-sei=TAKENAKA en-aut-mei=Hiroshi kn-aut-name=|m kn-aut-sei=| kn-aut-mei=m aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of Science and Technology, Kochi University kn-affil=mwHwn‹hЊw affil-num=2 en-affil=Department of Earth Sciences, Okayama University kn-affil=Rwwp@‹RȊww en-keyword=Okayama Plain kn-keyword=Okayama Plain en-keyword=Kojima Bay kn-keyword=Kojima Bay en-keyword=Microtremor array exploration kn-keyword=Microtremor array exploration en-keyword=S-wave velocity structure model kn-keyword=S-wave velocity structure model 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=15 cd-vols= no-issue= article-no= start-page=160 end-page=164 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=Verification of a Skin Electrical Impedance Model for Evaluating Indicators of Skin Barrier Function of Older Adults en-subtitle= kn-subtitle= en-abstract= kn-abstract=Skin barrier function has been quantitatively evaluated through trans-epidermal water loss, which has been difficult to measure in clinical settings owing to environmental factors and the measurement time. The thickness and surface water content of the stratum corneum are important indicators of skin barrier function, and current methods for measuring these two indicators are also difficult to implement in clinical settings. Therefore, we developed a model based on skin electrical impedance to estimate the thickness and water content of the stratum corneum, enabling measurement and estimation of these two indicators in a short time. In this study, we verified this model implemented in a portable skin electrical impedance measurement device for estimating the thickness and surface water content of the stratum corneum of the skin in older adults. Thirty-four older individuals were studied. The measurement electrodes were placed in contact with the forearm skin, and an alternating signal of two frequencies was applied to measure the impedance, from which the thickness and surface water content of the stratum corneum were estimated in approximately 5 s. The correlation coefficients between the estimated and measured thickness and between the estimated and measured surface water content were 0.732 and 0.604, respectively. Furthermore, the root mean square errors of the residuals for the thickness and surface water content were 1.66 ?m and 3.50 points, respectively, indicating that the model accurately estimated the thickness and surface water content of the stratum corneum, even in the skin of older adults. en-copyright= kn-copyright= en-aut-name=UEHARAOsamu en-aut-sei=UEHARA en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FUNAKIYuya en-aut-sei=FUNAKI en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NAKAMURATakao en-aut-sei=NAKAMURA en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Medical Engineering Laboratory, ALCARE Co., Ltd. kn-affil= affil-num=2 en-affil=Medical Engineering Laboratory, ALCARE Co., Ltd. kn-affil= affil-num=3 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=older adults kn-keyword=older adults en-keyword=stratum corneum thickness kn-keyword=stratum corneum thickness en-keyword=stratum corneum surface water content kn-keyword=stratum corneum surface water content END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=3 article-no= start-page=e72040 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=Effects of Overload on Imiquimod]Induced Psoriasis Model Mice: A Basic Experimental Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aim: Psoriasis is a skin disorder complicated by arthritis and enthesitis. The cytokines interleukin (IL)-17, IL-23, and tumor necrosis factor (TNF)- are reportedly key effectors of psoriasis. Additionally, gamma delta () T cells exacerbate inflammation by producing inflammatory cytokines such as IL-17 and TNF-. However, details regarding the mechanisms linking pathogenesis and mechanical stress remain unclear. This study aimed to investigate the effect of strenuous exercise on the pathology of psoriasis using mouse models of imiquimod (IMQ)-induced psoriasis.
Methods: Twenty mice were randomly assigned to four groups: IMQ???TRED? (control), IMQ???TRED+ (treadmill running mice), IMQ?+?TRED? group (IMQ treated mice), and IMQ?+?TRED+ group (IMQ treated and treadmill running mice). The tissue sections from back skin and thymus were immunostained with antibodies against IL-17, IL-23, and T cells. Shoulder sections were stained using hematoxylin and eosin, and Toluidine Blue and Picrosirius Red. Additionally, the shoulder tissue sections were immunostained with antibodies against TNF- and matrix metalloproteinase (MMP)-13. Serum cytokine level was measured to evaluate systemic inflammation.
Results: Strenuous exercise exacerbated pathological changes associated with psoriasis, including increased T cell infiltration and upregulated IL-17 and IL-23 expression in the skin, as well as enhanced T cell development and IL-17 expression in the thymus. Although strenuous exercise did not further worsen the modified PASI scores, histological and immunological markers of inflammation were significantly enhanced. Serum levels of TNF- and IL-17 were significantly elevated in IMQ-induced psoriasis model mice. Moreover, pathological changes induced by strenuous exercise were observed in the enthesis, including angiogenesis and upregulated expression of TNF- and MMP-13.
Conclusion: This study revealed that strenuous exercise exacerbates pathological changes in IMQ-induced psoriasis model mice. en-copyright= kn-copyright= en-aut-name=FurutaniTomoki en-aut-sei=Furutani en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaitoTaichi en-aut-sei=Saito en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkedaAsahi en-aut-sei=Ikeda en-aut-mei=Asahi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MashimaKenta en-aut-sei=Mashima en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YukihiroNatsumi en-aut-sei=Yukihiro en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KusakabeSatoki en-aut-sei=Kusakabe en-aut-mei=Satoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamichiRyo en-aut-sei=Nakamichi en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro 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= affil-num=1 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Okayama University Medical School Faculty of Medicine kn-affil= affil-num=4 en-affil=Okayama University Medical School Faculty of Medicine kn-affil= affil-num=5 en-affil=Okayama University Medical School Faculty of Medicine kn-affil= affil-num=6 en-affil=Okayama University Medical School Faculty of Medicine Okayama Japan kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Locomotive Pain Center, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=enthesis kn-keyword=enthesis en-keyword=psoriasis kn-keyword=psoriasis en-keyword=strenuous exercise kn-keyword=strenuous exercise END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=e70168 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=Mechanosensitive Ion Channel PIEZO1 Suppresses BMP2-Induced Ossification of the Annulus Fibrosus Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Major cause of low-back pain is intervertebral disc degeneration (IVDD), with mechanical stress playing a crucial role in its progression. A mechanosensitive ion channel, PIEZO1, is involved in various musculoskeletal tissues, but its role in the annulus fibrosus (AF) remains unclear. This study aimed to elucidate the function of PIEZO1 in AF cells under mechanical stimulation.
Methods: Primary rat AF cells were subjected to cyclic tensile strain (CTS) at low (2%) and high (12%) strain levels to investigate strain-dependent effects on osteogenic gene expression. We evaluated the effects of Piezo1, Piezo2, and Trpv4 knockdown by RNA interference to identify the upstream mechanotransducer. Furthermore, PIEZO1 was activated using the agonist Yoda1, followed by RNA-sequencing analysis and evaluation of its effects on BMP2-induced osteogenesis in rat AF cells. We also examined the effects of Yoda1 in primary human AF cells.
Results: Low-strain CTS significantly suppressed osteogenic marker expression, which was not observed with high strain. Piezo1 knockdown reversed this suppression, whereas Piezo2 and Trpv4 had no effect. Piezo1 activation by Yoda1 produced similar anti-osteogenic effects in both rat and human AF cells. RNA sequencing revealed the enrichment of ossification and calcineurin signaling pathways in rat cells. Furthermore, Piezo1 activation inhibited BMP2-induced osteogenesis and nuclear translocation of p-Smad1/5/9.
Conclusions: Piezo1 maintains AF cell homeostasis under mechanical stress by suppressing osteogenic changes via calcineurin-mediated inhibition of BMP signaling, which may represent a novel therapeutic target for IVDD. en-copyright= kn-copyright= en-aut-name=ShitozawaHisakazu en-aut-sei=Shitozawa en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamichiRyo en-aut-sei=Nakamichi en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=UedaMasataka en-aut-sei=Ueda en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoTaichi en-aut-sei=Saito en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OdaYoshiaki en-aut-sei=Oda en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakatoriRyo en-aut-sei=Takatori en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamashitaKazutaka en-aut-sei=Yamashita en-aut-mei=Kazutaka 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= affil-num=1 en-affil=Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=annulus fibrosus kn-keyword=annulus fibrosus en-keyword=calcification kn-keyword=calcification en-keyword=ossification kn-keyword=ossification en-keyword=PIEZO1 kn-keyword=PIEZO1 END start-ver=1.4 cd-journal=joma no-vol=57 cd-vols= no-issue=3 article-no= start-page=93 end-page=109 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260318 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Environmental Conservation Costs and Operational Efficiency: Evidence from Japanese Manufacturing Firms en-subtitle= kn-subtitle= en-abstract= kn-abstract=@This study investigates whether environmental conservation costs (ECC) support the operational effectiveness and financial stability of Japanese manufacturing firms. Using a balanced panel of 128 non-financial companies listed on the Tokyo Stock Exchange from 2010 to 2022, we manually collected firm-level ECC data based on the Ministry of the Environment, Japan's guidelines from sustainability reports and matched them with financial data from Compustat Global/S&P Capital IQ. Applying pooled ordinary least squares regression with firm-level clustered standard errors and winsorized variables, we examine two aspects of performance as measures of operating efficiency and profitability: asset turnover and profit margin. The results show that ECC is positively associated with asset turnover and profit margin, and that the effect is stronger in more profitable companies, substantiating the Resource-Based View that green practices generate competitiveness. These findings contribute to sustainability finance research by going beyond perceptual measures of environmental, social, and governance ratings, and measuring actual firm-level spending on environmental activities, thereby providing more nuanced insights into how environmental practices translate into actual financial performance. This study offers clear managerial and policy implications by showing that transparent environmental conservation costs improve disclosure quality and serve as a measure of improved efficiency and profitability. en-copyright= kn-copyright= en-aut-name=NazirYusra en-aut-sei=Nazir en-aut-mei=Yusra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TennojiyaTatsumasa en-aut-sei=Tennojiya en-aut-mei=Tatsumasa kn-aut-name=VJB kn-aut-sei=VJ kn-aut-mei=B aut-affil-num=2 ORCID= affil-num=1 en-affil=Doctoral student at Graduate school of humanities and social sciences, Okayama University kn-affil= affil-num=2 en-affil=Faculty of humanities and social sciences, Okayama University kn-affil= en-keyword=Environmental Accounting kn-keyword=Environmental Accounting en-keyword=Environmental Conservation Cost, Operating Efficiency kn-keyword=Environmental Conservation Cost, Operating Efficiency en-keyword=Profitability kn-keyword=Profitability en-keyword=Asset Turnover kn-keyword=Asset Turnover en-keyword=Sustainability kn-keyword=Sustainability en-keyword=Japanese Manufacturing Companies kn-keyword=Japanese Manufacturing Companies en-keyword=Resource-Based View kn-keyword=Resource-Based View END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=146 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260115 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=MMP-3 cleavage of Lamin A induces pro-migratory nuclear deformity, nucleophagy, and their autophagic secretion with extracellular vesicles in metastatic cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that cleave a plethora of substrates, including components of the extracellular matrix and cell-surface-associated proteins, as well as intracellular targets. MMPs have also been found in extracellular vesicles (EVs), such as exosomes. MMP-3 promotes tumor growth, epithelial-to-mesenchymal transition, genome instability, migration, invasion, and metastasis of cancer cells, and nuclear MMP-3 controls gene transcription. Intranuclear proteolysis by MMPs may significantly alter cancer progression. However, the nuclear substrates of MMP-3 have not been well investigated. In this study, we performed proteomic analyses to identify the nuclear substrates and EV proteins regulated by MMP-3. While rabidly metastatic colon cancer (LuM1) three-dimensionally cultured tumoroids secreted EVs containing 30 protein types, including Lamin A (LMNA), MMP-3, fibronectin (FN1), HSPA8 (Hsc70), -actin (ACTB), and vimentin (VIM), CRISPR/Cas9-based knockout of MMP-3 reduced the secretion of these proteins in EVs. Notably, EV-bound cleaved Lamin secretion was confirmed by immunoelectron microscopy. Also, MMP-3 formed proteolytic dimers via its hemopexin-like repeat domains in nuclei. Many nuclear MMP-3-binding proteins, including Lamin A/C, histones, topoisomerases, and hnRNPs, were screened by co-immunoprecipitation followed by proteomics. Proteolytic MMP-3 overexpression generated a C-terminal 30-kDa fragment of Lamin A, whose cleavage site was defined via structural analysis. MMP-3 digestion of Lamin A induced nuclear deformity (atypia) required for cell migration in confined space. The cleaved Lamin A and MMP-3 were transported with autophagosomes (LC3B+), nucleophagosomes, and amphisomes (CD63?+?LC3B+) and co-secreted with EVs. Proteolytic MMP-3 also induced nuclear speckles of Lamin A, suggesting their roles in transcription and splicing. Clinical analysis revealed that high expressions of MMP3 and LMNA were significantly seen in head and neck squamous cell carcinoma (HNSC) than in the other 16 cancer types, and predicted poor prognosis of patients suffering from HNSC, pancreatic, rectum and lung adenocarcinomas at specific stages. Immunohistochemistry revealed that nuclear MMP-3 and cleaved Lamin were significantly higher expressed in stage IV metastatic HNSC cases than in stage I non-metastatic cases. Taken together, MMP3-cleavage of Lamin A induces nuclear deformity, nucleophagy, and their autophagic co-secretion with EVs in metastatic cancer. Also, high expression of MMP-3 and secretion of Lamin A can predict poor prognosis in multiple cancer types at specific stages. en-copyright= kn-copyright= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TahaEman A. en-aut-sei=Taha en-aut-mei=Eman A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TiwariVikas en-aut-sei=Tiwari en-aut-mei=Vikas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakebeKatsuki en-aut-sei=Takebe en-aut-mei=Katsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InoueTomohiro en-aut-sei=Inoue en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=XingLizi en-aut-sei=Xing en-aut-mei=Lizi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkamotoKuniaki en-aut-sei=Okamoto en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=CalderwoodStuart K. en-aut-sei=Calderwood en-aut-mei=Stuart K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biochemistry, Faculty of Science, Ain Shams University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Council of Scientific & Industrial Research-Indian Institute of Toxicological Research kn-affil= affil-num=5 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of Technology kn-affil= affil-num=9 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= en-keyword=Lamin A (LMNA) kn-keyword=Lamin A (LMNA) en-keyword=Matrix metalloprotease (MMP) kn-keyword=Matrix metalloprotease (MMP) en-keyword=Proteolysis kn-keyword=Proteolysis en-keyword=Extracellular vesicle (EV) kn-keyword=Extracellular vesicle (EV) en-keyword=Exosome kn-keyword=Exosome en-keyword=Autophagy kn-keyword=Autophagy en-keyword=Amphisome kn-keyword=Amphisome en-keyword=Proteome kn-keyword=Proteome en-keyword=Nuclear deformity kn-keyword=Nuclear deformity en-keyword=Migration kn-keyword=Migration en-keyword=Metastatic cancer kn-keyword=Metastatic cancer en-keyword=Head and neck squamous cell carcinoma kn-keyword=Head and neck squamous cell carcinoma en-keyword=Colorectal cancer kn-keyword=Colorectal cancer END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=27 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between the incidence of infusion-related reactions by obinutuzumab and the dose of corticosteroid as premedication: a multicenter retrospective cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Premedication with corticosteroids is recommended for prophylaxis against infusion-related reactions (IRRs) caused by obinutuzumab despite a lack of solid evidence regarding the dose of corticosteroids.
Methods The incidence rates of IRR in the high-dose and low-dose corticosteroid groups were investigated and compared using Studentfs t-test.Univariable and multivariable logistic regression analyses were performed on patients to explore the risk of developing IRRs with obinutuzumab.
Results The incidence of IRRs in the high-dose and low-dose corticosteroid groups at the initial administration of obinutuzumab was 27.0% (41/152) and 48.4% (31/64), respectively, indicating that the high-dose group had a lower incidence of IRRs (p?=?0.002). The incidence of IRRs at the initial administration of obinutuzumab was significantly associated with the administration of first-generation histamine 1 receptor antagonist (OR?=?3.31, 95% CI: 1.16?9.47; reference: second-generation histamine 1 receptor antagonist), hydrocortisone (OR?=?7.21, 95% CI: 1.57?33.15; reference: dexamethasone), and methylprednisolone (OR?=?3.99, 95% CI :1.13?14.10; reference: dexamethasone), although no association was found with the lower dose of corticosteroids.
Conclusions Although no association was found between corticosteroid dosage and IRR when considering multiple factors, dexamethasone may be a better option than hydrocortisone or methylprednisolone for preventing IRR. Additionally, second-generation H1-receptor antagonists may be a better option than first-generation drugs. Certain combinations of premedications may influence infusion reaction incidence. en-copyright= kn-copyright= en-aut-name=OhtsuboTatsuya en-aut-sei=Ohtsubo en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatumotoSaori en-aut-sei=Matumoto en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItoKaori en-aut-sei=Ito en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SasaYuzuka en-aut-sei=Sasa en-aut-mei=Yuzuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TomishimaKosuke en-aut-sei=Tomishima en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DoteSatoshi en-aut-sei=Dote en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MakiharaKatuya en-aut-sei=Makihara en-aut-mei=Katuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WakasugiYoshinori en-aut-sei=Wakasugi en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MitsuieTsutomu en-aut-sei=Mitsuie en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamagiwaKouhei en-aut-sei=Yamagiwa en-aut-mei=Kouhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SatoKazuo en-aut-sei=Sato en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HasegawaHiroki en-aut-sei=Hasegawa en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UoshimaNobuhiko en-aut-sei=Uoshima en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KitahiroYumi en-aut-sei=Kitahiro en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TomoganeKanji en-aut-sei=Tomogane en-aut-mei=Kanji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Pharmacy, Japanese Red Cross Kyoto Daini Hospital kn-affil= affil-num=2 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacy, Japanese Red Cross Osaka Hospital kn-affil= affil-num=4 en-affil=Faculty of Pharmacy, Meijo University kn-affil= affil-num=5 en-affil=Department of Pharmacy, Kindai University Hospital kn-affil= affil-num=6 en-affil=Department of Pharmacy, Japanese Red Cross Kyoto Daiichi Hospital kn-affil= affil-num=7 en-affil=Department of Pharmacy, Kyoto-Katsura Hospital kn-affil= affil-num=8 en-affil=Department of Pharmacy, Yodogawa Christian Hospital kn-affil= affil-num=9 en-affil=Department of Pharmacy, Shiga University of Medical Science Hospital kn-affil= affil-num=10 en-affil=Department of Pharmacy, Japanese Red Cross Otsu Hospital kn-affil= affil-num=11 en-affil=Department of Pharmacy, Saiseikai Shiga Hospital kn-affil= affil-num=12 en-affil=Department of Pharmacy, Japan Baptist Hospital kn-affil= affil-num=13 en-affil=Department of Pharmacy, Rakuwakai Otowa Hospital kn-affil= affil-num=14 en-affil=Department of Hematology, Japanese Red Cross Kyoto Daini Hospital kn-affil= affil-num=15 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=16 en-affil=Department of Pharmacy, Japanese Red Cross Kyoto Daini Hospital kn-affil= en-keyword=Obinutuzumab kn-keyword=Obinutuzumab en-keyword=Infusion-related reaction kn-keyword=Infusion-related reaction en-keyword=Premedication kn-keyword=Premedication en-keyword=Corticosteroids kn-keyword=Corticosteroids en-keyword=Histamine 1 receptor antagonists kn-keyword=Histamine 1 receptor antagonists END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=1 article-no= start-page=32 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260102 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-world comparative effectiveness of sarilumab versus Janus kinase inhibitors as monotherapy in rheumatoid arthritis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Sarilumab (SAR), an interleukin-6 receptor inhibitor (IL-6Ri), and Janus kinase inhibitors (JAKi) are approved options for rheumatoid arthritis (RA) when methotrexate (MTX) cannot be used. Real-world evidence for MTX-free monotherapy remains limited.
Methods: We conducted a multicenter retrospective cohort study of RA patients receiving SAR or JAKi as MTX-free monotherapy. To reduce confounding, 1:1 propensity score matching was performed in the overall cohort (n?=?252, 126 per group) and separately within treatment-line strata: Phase 2 first-line biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs: 45 per group), Phase 3 second-line b/tsDMARDs (53 per group), and Phase 3???third-line b/tsDMARDs (47 per group). Outcomes over 12 months included drug retention, change in Clinical Disease Activity Index (CDAI), glucocorticoid (GC) tapering and discontinuation, low disease activity (LDA, CDAI???10), and safety profiles. Predictors of LDA were evaluated with logistic regression. This multicenter real-world.
Results: Across matched strata by prior b/tsDMARDs, retention and CDAI change did not differ significantly between SAR and JAKi through 12 months. When classified by cause, adverse events (AEs)-related discontinuation was higher with JAKi, yielding lower AE-specific retention. Both groups demonstrated GC sparing overtime, with a greater increase in GC discontinuation for SAR than for JAKi in Phase 2. Baseline predictors of achieving LDA at 12 months included higher C-reactive protein (CRP) and platelet count (Plt) in both groups, with additional associations of younger age and lower hemoglobin (Hb) in the SAR. In safety analyses, overall AEs were less frequent with SAR than with JAKi, driven by lower risks of infection including herpes zoster, while other categories were similarly infrequent.
Conclusion: SAR and JAKi showed no statistically significant differences in 12-month retention or disease control in MTX-free monotherapy settings. Higher CRP and Plt with lower Hb, particularly in younger patients, identified better response to SAR and support biomarker guided selection between IL-6Ri and JAKi. In Phase 2, GC discontinuation with SAR suggests a practical strategy to reduce AEs while maintaining efficacy. Prospective studies should validate these findings and define actionable thresholds. en-copyright= kn-copyright= en-aut-name=NozakiYuji en-aut-sei=Nozaki en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KishimotoKazuya en-aut-sei=Kishimoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItamiTetsu en-aut-sei=Itami en-aut-mei=Tetsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomitaDaisuke en-aut-sei=Tomita en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WadaYumiko en-aut-sei=Wada en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KotaniTakuya en-aut-sei=Kotani en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeuchiTohru en-aut-sei=Takeuchi en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HidakaToshihiko en-aut-sei=Hidaka en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HinoShoichi en-aut-sei=Hino en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyamotoToshiaki en-aut-sei=Miyamoto en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MiyakeHirofumi en-aut-sei=Miyake en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HattaKazunari en-aut-sei=Hatta en-aut-mei=Kazunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MamotoKenji en-aut-sei=Mamoto en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamadaYutaro en-aut-sei=Yamada en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OkanoTadashi en-aut-sei=Okano en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OkanoTakaichi en-aut-sei=Okano en-aut-mei=Takaichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SaegusaJun en-aut-sei=Saegusa en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HoritaMasahiro en-aut-sei=Horita en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KinoshitaKoji en-aut-sei=Kinoshita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=RaiShinya en-aut-sei=Rai en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Hematology and Rheumatology, Kindai University Faculty of Medicine kn-affil= affil-num=2 en-affil=Department of Hematology and Rheumatology, Kindai University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Hematology and Rheumatology, Kindai University Faculty of Medicine kn-affil= affil-num=4 en-affil=Department of Hematology and Rheumatology, Kindai University Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University kn-affil= affil-num=6 en-affil=Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University kn-affil= affil-num=7 en-affil=Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University kn-affil= affil-num=8 en-affil=Rheumatology Center, Miyazaki Zenjinkai Hospital kn-affil= affil-num=9 en-affil=Department of Rheumatology and Clinical Immunology, Izumi City General Medical Center kn-affil= affil-num=10 en-affil=Miyamoto Internal Medicine and Rheumatology Clinic kn-affil= affil-num=11 en-affil=Department of General Internal Medicine, Tenri Hospital kn-affil= affil-num=12 en-affil=Department of General Internal Medicine, Tenri Hospital kn-affil= affil-num=13 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=14 en-affil=Center for Senile Degenerative Disorders (CSDD), Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Center for Senile Degenerative Disorders (CSDD), Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Orthopaedic Surgery, Faculty of Medical Development Field, Okayama University kn-affil= affil-num=19 en-affil=Locomotive Pain Center, Faculty of Medical Development Field, Okayama University kn-affil= affil-num=20 en-affil=Department of Hematology and Rheumatology, Kindai University Faculty of Medicine kn-affil= affil-num=21 en-affil=Department of Hematology and Rheumatology, Kindai University Faculty of Medicine kn-affil= en-keyword=Rheumatoid arthritis kn-keyword=Rheumatoid arthritis en-keyword=Methotrexate kn-keyword=Methotrexate en-keyword=Biological DMARDs kn-keyword=Biological DMARDs END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=e006392 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=Dental infection is associated with early relapse in patients with ANCA-associated vasculitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic autoimmune disease where infections can trigger relapses. Dental infections, being common and associated with systemic inflammation, may play a role in AAV relapse, though their impact remains unclear. We aimed to evaluate the association between severe dental infections and early relapse in patients with AAV.
Methods This retrospective cohort study included patients newly diagnosed with AAV between January 2011 and July 2022. Patients with severe dental infections requiring tooth extraction were placed in the dental infection group, while the remaining patients were assigned to the control group. The primary outcome was defined as either vasculitis relapse or all-cause mortality within 1 year of treatment initiation. Adjusted HRs (aHRs) and 95% CIs were estimated using Cox proportional hazards models.
Results A total of 93 patients were enrolled with a median age of 74 years. 41 patients (44.1%) had severe dental infections in this cohort. Over the 1-year follow-up period, 13 patients experienced a relapse and two died, resulting in a composite event rate of 20.9 per 100 person-years. Dental infection was independently associated with the composite outcome (aHR, 3.78 (95% CI 1.13 to 12.66); p=0.031). Exploratory analysis indicated that composite outcome rates were similar regardless of tooth extraction among patients with dental infections.
Conclusions Severe dental infections were associated with increased risk of early relapse or mortality in AAV. These findings highlight the importance of early dental evaluation in AAV management. en-copyright= kn-copyright= en-aut-name=NawachiShoichi en-aut-sei=Nawachi en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatsuyamaTakayuki en-aut-sei=Katsuyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyawakiYoshia en-aut-sei=Miyawaki en-aut-mei=Yoshia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Sakamoto-TokunagaMoe en-aut-sei=Sakamoto-Tokunaga en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KubotaNatsuki en-aut-sei=Kubota en-aut-mei=Natsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TerajimaYuya en-aut-sei=Terajima en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoKazuya en-aut-sei=Matsumoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiroseKei en-aut-sei=Hirose en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakadoiTakato en-aut-sei=Nakadoi en-aut-mei=Takato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Hirata-WatanabeManami en-aut-sei=Hirata-Watanabe en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatayamaYu en-aut-sei=Katayama en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HayashiKeigo en-aut-sei=Hayashi en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WatanabeHaruki en-aut-sei=Watanabe en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatsuyamaEri en-aut-sei=Katsuyama en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=Takano-NarazakiMariko en-aut-sei=Takano-Narazaki en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TsujiShigetomo en-aut-sei=Tsuji en-aut-mei=Shigetomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SadaKen-Ei en-aut-sei=Sada en-aut-mei=Ken-Ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue= article-no= start-page=e79545 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260302 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prescription Support Practice for Pharmacy Students: Pre-Post Educational Intervention Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: In the field of team-based care, pharmacists are vital for optimizing medication therapy. However, many medical professionals lack the opportunity to learn how to propose prescription changes with precision.
Objective: This study aimed to address this knowledge gap by developing and assessing a new educational program for pharmacy students focused on prescription support and interprofessional collaboration.
Methods: We recruited 191 fifth-year pharmaceutical students during the 2022]2024 academic years. The program featured a 7-day intensive curriculum that included learning how to assist with prescriptions, analyzing clinical data, and engaging in role-playing exercises. A web-based questionnaire and a paper test were used to evaluate studentsf awareness and knowledge both before and after the program. Statistical analyses were performed to verify the significance of changes; we utilized the Wilcoxon signed-rank test for the ordinal data derived from the specific behavioral objectives and 2-tailed paired t tests for the interval data from the knowledge tests. The magnitude of change was quantified using r for Wilcoxon tests and Cohen dz for 2-tailed t tests, with 95% CI calculated to ensure the stability and reliability of the observed results.
Results: Analysis of the primary outcome specific behavioral objectives revealed statistically significant effects across all items (Wilcoxon signed-rank test; P<.001). Effect sizes (r=0.505]0.835) ranged from moderate to large, with particularly large effects observed in identifying contents issue (r=0.835, 95% CI 0.126-0.330; P<.001). Knowledge test scores showed significant improvement in the following 3 subjects: pharmacology (r=?0.504, 95% CI ?0.215 to 0.127; P<.001), organic chemistry (r=0.254, 95% CI ?0.148 to ?0.193; P=.004), and communication (r=0.221, 95% CI ?0.151 to ?0.190; P=.01). No significant changes were observed in pathology or pharmacokinetics.
Conclusions: This program provides strong evidence that practical, hands-on learning with hospital pharmacists helps improve pharmacy studentsf professional skills and optimize pharmaceutical therapies in interprofessional care. By teaching pharmacists to effectively propose prescription changes, the program equips them to become integral members of interprofessional care, ultimately leading to optimized pharmaceutical care for patients. en-copyright= kn-copyright= en-aut-name=AizawaFuka en-aut-sei=Aizawa en-aut-mei=Fuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YagiKenta en-aut-sei=Yagi en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=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=TakahashiShimon en-aut-sei=Takahashi en-aut-mei=Shimon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=ShinomiyaKazuaki en-aut-sei=Shinomiya en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NiimuraTakahiro en-aut-sei=Niimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=GodaMitsuhiro en-aut-sei=Goda en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawadaKei en-aut-sei=Kawada en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshizawaKeisuke en-aut-sei=Ishizawa en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital kn-affil= affil-num=2 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=3 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=6 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pharmaceutical Care and Clinical Pharmacy, Tokushima Bunri University kn-affil= affil-num=8 en-affil=Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital kn-affil= affil-num=9 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=10 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=11 en-affil=Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital kn-affil= en-keyword=academic detailing kn-keyword=academic detailing en-keyword=pharmaceutical clinical practice kn-keyword=pharmaceutical clinical practice en-keyword=prescription support kn-keyword=prescription support en-keyword=professional education kn-keyword=professional education en-keyword=Interprofessional care kn-keyword=Interprofessional care END start-ver=1.4 cd-journal=joma no-vol=115 cd-vols= no-issue=3 article-no= start-page=117345 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202607 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Investigation of the cefazolin inoculum effect in blood culture-isolated methicillin-susceptible Staphylococcus aureus strains: A Japanese multicenter study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Cefazolin inoculum effect (CInE) is a microbiological phenomenon where the MIC of cefazolin against methicillin-susceptible Staphylococcus aureus (MSSA) strains increases with higher bacterial volumes.
Method: We retrospectively investigated the prevalence and characteristics of the CInE among MSSA strains isolated from blood cultures at three Japanese hospitals. The collected isolates were screened for blaZ using PCR, and the cefazolin minimum inhibitory concentration (MIC) for the blaZ-positive MSSA isolates was measured at standard and high inoculum volumes. CInE-positive MSSA strains were defined as those with a cefazolin MIC ?16 g/mL at 107 CFU/mL and ?8 g/mL at 105 CFU/mL. In these blaZ-positive strains, we performed blaZ typing and tested a modified nitrocefin-based rapid examination to detect the CInE.
Results: We collected 329 MSSA strains isolated from blood cultures. Of these, 96 (29.2%) were positive for the blaZ gene, with the following genotypes: type A (15, 15.6%), type B (3, 3.1%), type C (77, 80.2%), type D (0, 0.0%), and non-type (1, 1.0%). Among 96 blaZ-positive MSSA isolates, 11 exhibited the CInE, all of which harbored blaZ type A. The rapid nitrocefin test detected CInE positivity with high sensitivity (100%), specificity (94.1%), and diagnostic accuracy (94.8%).
Conclusion: This study highlighted the low prevalence of CInE-presenting MSSA isolates in Japan. When the cefazolin MIC is ?1 g/mL or the penicillin G MIC is ?0.25 g/mL, the rapid nitrocefin test may be useful for considering the CInE in patients with high bacterial volume MSSA infections. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 ORCID= en-aut-name=OgawaSakura en-aut-sei=Ogawa en-aut-mei=Sakura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KoyanagiNorihito en-aut-sei=Koyanagi en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItoYuji en-aut-sei=Ito en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoganemaruHiroshi en-aut-sei=Koganemaru en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshidaAtsushi en-aut-sei=Yoshida en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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 Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital 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 Clinical Laboratory, Chutoen General Medical Center kn-affil= affil-num=7 en-affil=Department of General Internal Medicine, Chutoen General Medical Center kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, Tokyo Metropolitan Institute for Geriatrics and Gerontology kn-affil= affil-num=9 en-affil=Department of Infectious Diseases, Tokyo Metropolitan Institute for Geriatrics and Gerontology kn-affil= affil-num=10 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=blaZ kn-keyword=blaZ en-keyword=Cefazolin inoculum effect kn-keyword=Cefazolin inoculum effect en-keyword=Methicillin-susceptible Staphylococcus aureus kn-keyword=Methicillin-susceptible Staphylococcus aureus en-keyword=Nitrocefin rapid test kn-keyword=Nitrocefin rapid test en-keyword=-lactamase kn-keyword=-lactamase 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=20260203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-world six-month outcomes after switching from aflibercept 2 mg to aflibercept 8 mg for neovascular age-related macular degeneration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose To investigate 6-month outcomes in eyes with neovascular age-related macular degeneration (nAMD) switched from intravitreal aflibercept 2 mg to intravitreal aflibercept 8 mg.
Study design Retrospective observational study.
Methods We reviewed records of consecutive nAMD eyes switched from aflibercept 2 mg to 8 mg. In eyes continuing aflibercept 8 mg, best-corrected visual acuity (BCVA), treatment intervals, and anatomical/exudative parameters were evaluated at 6 months. In eyes that could not continue, reasons for discontinuation were examined.
Results Forty-four eyes from 44 patients were included. At 6 months, 35 eyes (79.5%) continued and 9 (20.5%) discontinued aflibercept 8 mg. Discontinuing eyes had significantly shorter pre-switch treatment intervals and more frequent prior therapies than continuing eyes. In the continuation group, BCVA remained stable (median 0.05 to 0.00 logMAR, P = 0.351), while the treatment interval was significantly extended (median 7.0 to 9.0 weeks, P < 0.001). Central retinal thickness and pigment epithelial detachment height decreased significantly (P = 0.035 and P = 0.021, respectively). The proportion of eyes with subretinal fluid significantly decreased from 74.3 to 37.1% (P = 0.003). Of the discontinuations, 4 were due to worsening exudation and 5 to inability to extend to ?8 weeks as required by labeling. No intraocular inflammation or serious adverse events occurred.
Conclusions Switching to aflibercept 8?mg achieved anatomical improvements and longer treatment intervals in ~80% of nAMD cases, suggesting it may be a useful alternative to aflibercept 2 mg. However, continuation may be difficult in refractory cases requiring frequent injections before switching. en-copyright= kn-copyright= en-aut-name=KindoHiroya en-aut-sei=Kindo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HosokawaMio Morizane en-aut-sei=Hosokawa en-aut-mei=Mio Morizane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OuchiChihiro en-aut-sei=Ouchi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HayashiJunko en-aut-sei=Hayashi en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Aflibercept 8 mg kn-keyword=Aflibercept 8 mg en-keyword=Neovascular age-related macular degeneration kn-keyword=Neovascular age-related macular degeneration en-keyword=Treat-and-extend kn-keyword=Treat-and-extend en-keyword=Switching kn-keyword=Switching en-keyword=Treatment interval kn-keyword=Treatment interval END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=6 article-no= start-page=oeaf162 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=Sex differences in the progression of cardiovascular?kidney?metabolic syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims Cardiovascular?kidney?metabolic (CKM) syndrome is a novel disease concept; however, sex differences in its progression remain uncertain. This study aimed to quantify the risk of cardiovascular disease (CVD) events across CKM stages and to explore sex differences in this association.
Methods and results We included 1 332 436 individuals (581 423 males and 751 013 females) from the DeSC database between 2014 and 2023 who had no prior CVD (i.e. CKM Stage 4). CKM stages were categorized as follows: Stage 0 (no CKM risk factors); Stage 1 (excess or dysfunctional adiposity); Stage 2 [metabolic risk factors and chronic kidney diseases (CKD)], and Stage 3 (subclinical CVD). We used Cox models to examine the association of CKM stages with the risk of CVD events (newly developed CKM Stage 4), including myocardial infarction, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The progression from CKM Stages 0 to 3 showed a dose-dependent increase in adjusted hazard ratios (HR) for developing CVD events, with the highest risk at Stage 3 [1.85 (95% CI: 1.80?1.90)]. A similar pattern was observed in both males and females. However, the magnitude of associations for CKM stages 1?3 differed between the sexes: HR by Stage 1, 1.12 (1.04?1.21) vs. 1.12 (1.07?1.16); by Stage 2, 1.78 (1.69?1.88) vs. 1.43 (1.39?1.48); by Stage 3, 1.99 (1.89?2.10) vs. 1.82 (1.76?1.88); and P-for-interaction values were 0.87, < 0.001, and 0.005, respectively.
Conclusion In this large nationwide cohort, CKM stage progression was associated with higher CVD risk in both sexes, with modest sex-specific differences. These findings highlight the value of CKM staging for early risk assessment, regardless of sex. en-copyright= kn-copyright= en-aut-name=TayaSatoshi en-aut-sei=Taya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanekoHidehiro en-aut-sei=Kaneko en-aut-mei=Hidehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MizunoAtsushi en-aut-sei=Mizuno en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KoToshiyuki en-aut-sei=Ko en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=JimbaTakahiro en-aut-sei=Jimba en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AzegamiTatsuhiko en-aut-sei=Azegami en-aut-mei=Tatsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkadaAkira en-aut-sei=Okada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiuKatsuhito en-aut-sei=Fujiu en-aut-mei=Katsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakedaNorifumi en-aut-sei=Takeda en-aut-mei=Norifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MoritaHiroyuki en-aut-sei=Morita en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HayashiKaori en-aut-sei=Hayashi en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NodeKoichi en-aut-sei=Node en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NangakuMasaomi en-aut-sei=Nangaku en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YasunagaHideo en-aut-sei=Yasunaga en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TakedaNorihiko en-aut-sei=Takeda en-aut-mei=Norihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Advanced Cardiology, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiology, Medical Quality Management Office, QI Center, St. Luke's International Hospital kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=10 en-affil=Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=11 en-affil=Department of Cardiovascular Medicine, The University of Tokyo kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, The University of Tokyo kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, The University of Tokyo kn-affil= affil-num=14 en-affil=Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=15 en-affil=Department of Cardiovascular Medicine, Saga University kn-affil= affil-num=16 en-affil=Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=17 en-affil=Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo kn-affil= affil-num=18 en-affil=Department of Cardiovascular Medicine, The University of Tokyo kn-affil= affil-num=19 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Cardiovascular?kidney?metabolic syndrome kn-keyword=Cardiovascular?kidney?metabolic syndrome en-keyword=Cardiovascular disease kn-keyword=Cardiovascular disease en-keyword=Sex difference kn-keyword=Sex difference END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=888 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=TRPV2 in muscle satellite cells is crucial for skeletal muscle remodelling en-subtitle= kn-subtitle= en-abstract= kn-abstract=Skeletal muscle remodelling relies on muscle stem cells (MuSCs) for regeneration after injury and hypertrophy in response to mechanical loading. However, the mechanisms that trigger MuSC activation and proliferation remain unclear. Transient receptor potential vanilloid 2 (TRPV2) ion channels respond to insulin-like growth factor-1 and mechanical stimuli to regulate the biological characteristics of various cells. Using a temporally inducible MuSC-specific conditional knockout (cKO) mouse, we show that TRPV2 regulates MuSC function and is essential for muscle remodelling. In cultured myofibre, MuSCs express TRPV2 and exhibit Ca2+ responses to the TRPV2 agonists 2-aminoethoxydiphenyl borate and probenecid, which are abolished upon TRPV2 deletion. TRPV2-deficient MuSCs exhibit reduced paired box 7 (Pax7) expression and impaired proliferation, suggesting TRPV2 is a factor that regulates the early stage of MuSC function. Myotube formation in MuSCs was enhanced by overexpression of TRPV2 and suppressed by TRPV2 deficiency, suggesting that TRPV2 is a factor that promotes myogenesis. Muscle-administered cardiotoxin promoted muscle regeneration and resulted in the appearance of numerous Pax7-positive MuSCs between myofibres. MuSC-specific TRPV2 cKO mice exhibit substantially impaired muscle regeneration after cardiotoxin-induced injury, drastically reducing Pax7-positive MuSCs between myofibres. In floxed mice, mechanical loading via synergist ablation induces hypertrophy and greatly increases the number of myonuclei per myofibre. In contrast, MuSC-specific TRPV2 cKO mice show no changes in myofibre thickness or nuclear number, either at baseline or after mechanical loading. Mechanical loading of floxed mice increased TRPV2+/Pax7+ double-positive MuSCs, but MuSC-specific TRPV2 cKO mice showed no change. Additionally, MuSCs exhibit Ca2+ responses to hypo-osmotic stimuli, which are suppressed by TRPV2 inhibitors and TRPV2 deletion, suggesting that MuSCs exhibit TRPV2-dependent mechanical responses. These results establish TRPV2 as a critical regulator of MuSC-mediated muscle remodelling, an important finding that may lead to therapeutic strategies for muscle repair and adaptation. en-copyright= kn-copyright= en-aut-name=ChenYanzhu en-aut-sei=Chen en-aut-mei=Yanzhu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatanosakaKimiaki en-aut-sei=Katanosaka en-aut-mei=Kimiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShibuyaMakoto en-aut-sei=Shibuya en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DongYubing en-aut-sei=Dong en-aut-mei=Yubing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhangLidan en-aut-sei=Zhang en-aut-mei=Lidan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KanagawaMotoi en-aut-sei=Kanagawa en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FukadaSo-ichiro en-aut-sei=Fukada en-aut-mei=So-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatanosakaYuki en-aut-sei=Katanosaka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Laboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of Osaka kn-affil= affil-num=6 en-affil=Department of Cell Biology and Molecular Medicine, Ehime University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Laboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of Osaka kn-affil= affil-num=8 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=411 cd-vols= no-issue=1 article-no= start-page=22 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=The impact of liver transection depth on surgical difficulty in robotic versus laparoscopic limited liver resection (TAKUMI-5) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Although robotic liver resection (RLR) has gained popularity worldwide, limited liver resection remains the mainstay of RLR. This study aimed to investigate the effect of parameters, including liver transection depth (LTD), on surgical difficulty in limited RLR compared with limited laparoscopic liver resection (LLR).
Methods This retrospective study included 105 patients who underwent limited RLR (n?=?56) or LLR (n?=?49) at our institution between January 2018 and December 2024. After comparing outcomes of RLR and LLR, multivariate analyses were performed to examine effect of LTD on surgical difficulty (defined as prolonged operative time). Moreover, outcomes stratified by LTD cut-off values were compared between the groups.
Results Median LTD was similar between groups (RLR vs. LLR: 2.6 vs. 2.6 cm, P?=?0.77). LTD was significantly correlated with operative time for both procedures (RLR, R? = 0.07, P?=?0.042; LLR, R? = 0.08, P?=?0.046). Multivariate analyses demonstrated that LLR (odds ratio, 6.9; P??2.5 cm), the RLR group had significantly shorter operative time (145 vs. 231 min, P? Conclusion This study investigated impact of LTD on surgical outcomes in patients who underwent limited RLR compared to those who underwent limited LLR. LTD may be a useful parameter for estimating surgical difficulty in limited RLR. Moreover, robotic surgery may be favorable for deeper and limited liver resections. en-copyright= kn-copyright= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItoAtene en-aut-sei=Ito en-aut-mei=Atene kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiyamaTakeyoshi en-aut-sei=Nishiyama en-aut-mei=Takeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YokoyamaShohei en-aut-sei=Yokoyama en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Robotic surgery kn-keyword=Robotic surgery en-keyword=Laparoscopic surgery kn-keyword=Laparoscopic surgery en-keyword=Limited liver resection kn-keyword=Limited liver resection en-keyword=Textbook outcome kn-keyword=Textbook outcome END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=10 article-no= start-page=e70269 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=D3 lymph node dissection in colon cancer patients aged 90?years and over: Is it justified? A multi]institutional retrospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim: The oncological benefit of D3 lymph node dissection (D3 LND) for colon cancer in patients aged ?90?years remains unclear. This study aimed to evaluate the impact of D3 LND on outcomes in this specific, vulnerable population.
Method: This retrospective cohort study evaluated 166 patients aged ?90?years with pathological Stages II?III colon cancer undergoing non-D3 or D3 LND from a multicentre database (2011?2022). Postoperative complications, overall survival and cancer-specific survival were compared between LND groups using propensity score-weighted analyses.
Results: D3 LND group had significantly more females and laparoscopic procedures. Operation time was longer, and blood loss was lower in the D3 LND group. Postoperative complications and severe complications were significantly fewer, and postoperative hospital stay was shorter in the D3 LND group. The number of harvested lymph nodes and distal margin was significantly higher in the D3 group. While unadjusted analysis showed better overall survival with D3 LND (p? Conclusion: In nonagenarian colon cancer patients, D3 LND is safe and feasible without increasing complications, but lacks survival benefit. Careful consideration is warranted, and high-quality D2 LND must be consistently ensured when limited surgery is chosen. 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=TakanagaSatoe en-aut-sei=Takanaga en-aut-mei=Satoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=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=ToshimaToshiaki en-aut-sei=Toshima en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 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=10 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, Kochi Health Sciences Center kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Medical Development Field, Okayama University 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 Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil= kn-affil= en-keyword=colon cancer kn-keyword=colon cancer en-keyword=lymph node dissection kn-keyword=lymph node dissection en-keyword=nonagenarian kn-keyword=nonagenarian en-keyword=postoperative complication kn-keyword=postoperative complication en-keyword=survival benefit kn-keyword=survival benefit 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=20260225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Overexpression of Escherichia coli yaiX Confers Multidrug Resistance and Enhances Virulence in the Silkworm Infection Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=The emergence of bacteria with both antimicrobial resistance and high virulence has become a global health concern, underscoring the urgent need to elucidate the molecular basis underlying these traits. Here, we employed the silkworm (Bombyx mori) infection model, which is suitable for high-throughput screening, together with an Escherichia coli library containing plasmid clones of all genes from strain W3110, to identify genes whose overexpression enhances virulence. We found that overexpression of the uncharacterized protein YaiX promoted bacterial proliferation in silkworms and increased host lethality. Compared with the empty-vector control, the YaiX-overexpressing strain exhibited resistance to multiple antimicrobial agents with diverse mechanisms of action, including -lactams, tetracyclines, fluoroquinolones, aminoglycosides, cationic surfactants, and hydrogen peroxide. Sequence analysis revealed that amino acids 18?52 of YaiX contain a transferase hexapeptide domain predicted to form a left-handed parallel -helix. Overexpression of YaiX mutants lacking regions outside this domain conferred ampicillin resistance, whereas deletion of the hexapeptide domain abolished this phenotype. RNA sequencing and GO enrichment analyses further indicated that YaiX overexpression altered the expression of genes encoding RNA-binding proteins and porins. These findings suggest that YaiX overexpression, through its hexapeptide domain, modulates gene expression and contributes to both multidrug resistance and enhanced virulence in E. coli. en-copyright= kn-copyright= en-aut-name=HonguKinuka en-aut-sei=Hongu en-aut-mei=Kinuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KosakiTomoki en-aut-sei=Kosaki en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=FurutaKazuyuki en-aut-sei=Furuta en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KaitoChikara en-aut-sei=Kaito en-aut-mei=Chikara 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=Research Center for Intestinal Health Science, 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= en-keyword=Escherichia coli kn-keyword=Escherichia coli en-keyword=hexapeptide domain kn-keyword=hexapeptide domain en-keyword=multidrug resistance kn-keyword=multidrug resistance en-keyword=pseudogene function kn-keyword=pseudogene function en-keyword=RNA]seq kn-keyword=RNA]seq en-keyword=silkworm infection model kn-keyword=silkworm infection model en-keyword=virulence kn-keyword=virulence en-keyword=yaiX kn-keyword=yaiX 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? 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= cd-vols= no-issue= article-no= start-page= end-page= 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=Early C-reactive protein as a predictive biomarker for postoperative complications following robot-assisted surgery for rectal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=This retrospective cohort study aimed to assess the predictive value of early postoperative C-reactive protein (CRP) levels for complications following robot-assisted rectal surgery (RARS) for rectal cancer. We analyzed data from 117 consecutive patients who underwent elective RARS at Okayama University Hospital between September 2020 and January 2025. Serum CRP levels were routinely measured preoperatively and on postoperative days (POD) 1 and 4. The primary outcome was the occurrence of any postoperative complication within 30 days, classified according to the Clavien?Dindo grading system. Postoperative complications were observed in 26 patients, representing 22.2% of the cohort. Univariate analysis revealed that several factors were significantly associated with complications, including older age, higher ASA score, neoadjuvant therapy, stoma creation, prolonged operative time, and elevated CRP levels on POD1 and POD4. Notably, multivariate logistic regression analysis identified POD1 CRP as a robust independent predictor of overall postoperative complications (adjusted odds ratio 0.77, 95% confidence interval (CI) [0.63?0.93], p? Methods: This cross-sectional multicentre study surveyed 133 adults with DS (mean age 50.1?years) residing in 45 welfare facilities across Japan in 2019. Dementia was diagnosed by a consensus panel of physicians using established criteria (DSM-5, ICD-10, DC-LD) after comprehensive assessments, including the Japanese version of the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID-J). Logistic regression analysis was performed to identify factors independently associated with dementia.
Results: Forty-six participants (34.6%) were diagnosed with dementia. The prevalence rose sharply with age: 0% in their 30s, 30.8% in their 40s, 31.6% in their 50s and 65.5% in their 60s. After adjusting for covariates, older age, female sex, dyslipidaemia and visual impairment were independently associated with dementia.
Conclusions: This study, the largest of its kind in Asia, confirms a high prevalence of dementia in institutionalized Japanese adults with DS. Crucially, this study is the first to identify dyslipidaemia and visual impairment as independent and potentially modifiable risk factors in this population. These findings highlight tangible targets for clinical interventions aimed at mitigating dementia risk in people with DS. en-copyright= kn-copyright= en-aut-name=TakenoshitaShintaro en-aut-sei=Takenoshita en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=InoueTomokazu en-aut-sei=Inoue en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KurozumiTaku en-aut-sei=Kurozumi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=KuwanoRyozo en-aut-sei=Kuwano en-aut-mei=Ryozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuemitsuShigeru en-aut-sei=Suemitsu en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso kn-affil= affil-num=4 en-affil=Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso kn-affil= affil-num=5 en-affil=Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso kn-affil= affil-num=7 en-affil=Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso kn-affil= END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=1 article-no= start-page=72 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260227 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Preferential sacral fracture sites in fragility fractures of the pelvis type IVb and comparison of internal fixation methods: CT-based morphological mapping and finite element analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Fragility fractures of the pelvis (FFP) classified as Rommens-Hoffman type IVb are associated with spinopelvic dissociation and are generally considered to require surgical intervention. This study aimed to clarify the localization patterns of FFP type IVb and compare the biomechanical stability of different internal fixation techniques.
Methods In this retrospective study, morphologic mapping of sacral fracture lines was performed in 36 patients with FFP type IVb. Based on the mapping results, a finite element (FE) model of FFP type IVb was developed to evaluate the biomechanical stability of ilio-sacral screw (ISS) fixation, trans-sacral screw (TSS) fixation, spinopelvic fixation (SPF; On each side, L5 pedicle screw was connected to two iliac screws with a rod, and the bilateral constructs were linked using a cross-connector.), and bilateral triangular fixation (one TSS at S1 combined with SPF mentioned above) using finite element analysis (FEA).
Results Morphologic mapping showed that the sacrum fracture transverse line tended to pass between the S1-2 transverse lines. Although bilateral triangular fixation and SPF provided the highest stability in both U-type and H-type fractures, a TSS for U-type and two TSSs for H-type also demonstrated comparable levels of stability. ISS-based methods showed greater displacements.
Conclusion TSS-based fixation may provide stability comparable to bilateral triangular fixation and SPF in FFP type IVb, with less invasiveness when anatomy permits. Further studies are needed to optimize treatment strategies for this complex injury. en-copyright= kn-copyright= en-aut-name=NaniwaShuichi en-aut-sei=Naniwa en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YorimitsuMasanori en-aut-sei=Yorimitsu en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasegawaTsubasa en-aut-sei=Hasegawa en-aut-mei=Tsubasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AndoTeruhiko en-aut-sei=Ando en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkudaRyuichiro en-aut-sei=Okuda en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuokaShiro en-aut-sei=Fukuoka en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MochizukiYusuke en-aut-sei=Mochizuki en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamakawaYasuaki en-aut-sei=Yamakawa en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=HanakawaShiro en-aut-sei=Hanakawa en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Musculoskeletal Traumatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=7 en-affil=Department of Emergency Health Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Kochi Health Sciences Center kn-affil= affil-num=9 en-affil=Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Okayama Saidaiji Hospital kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Fragility fractures of the pelvis kn-keyword=Fragility fractures of the pelvis en-keyword=Spinopelvic dissociation kn-keyword=Spinopelvic dissociation en-keyword=Finite element analysis kn-keyword=Finite element analysis en-keyword=Internal fixation kn-keyword=Internal fixation 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=25 cd-vols= no-issue=1 article-no= start-page=908 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognostic value of right atrial strain in patients with chronic heart failure en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims Right ventricular dysfunction is a well-established prognostic marker in patients with heart failure (HF). However, the prognostic significance of right atrial (RA) function remains unclear. Given its sensitivity to systemic congestion, RA function may provide additional insights into HF disease progression and management. This study aimed to investigate whether RA reservoir function serves as an independent prognostic indicator in patients with chronic HF.
Methods A total of 613 patients with chronic HF and a left ventricular (LV) ejection fraction of less than 50% who underwent echocardiographic assessment at Okayama University Hospital between January 2018 and March 2023 were included (median age: 68 (58?76) years; 69% male). RA reservoir function was quantified using two-dimensional speckle-tracking echocardiography. The primary endpoint was cardiovascular death or HF-related hospitalization. Kaplan?Meier survival analysis was performed to examine the association between RA reservoir function and clinical outcomes.
Results During a median follow-up period of 41 months (range: 12?91 months), 119 patients experienced cardiac events. Compared with event-free patients, those with cardiac events exhibited a significantly larger RA maximum volume index (38 mL/m2 vs. 31 mL/m2, P??20%, even without RA volume enlargement (log-rank test, P? Conclusions In patients who experienced adverse cardiac events, a reduced RASr and an increased RA maximum volume were observed. Furthermore, a reduced RASr was independently associated with an increased risk of cardiovascular death and HF-related hospitalization in patients with chronic HF and LV dysfunction. These findings indicate that RASr may serve as a valuable prognostic marker for the risk stratification and management of chronic HF. en-copyright= kn-copyright= en-aut-name=NakayamaRie en-aut-sei=Nakayama en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakayaYoichi en-aut-sei=Takaya en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishiharaTakahiro en-aut-sei=Nishihara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TohNorihisa en-aut-sei=Toh en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ToruMiyoshi en-aut-sei=Toru en-aut-mei=Miyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= en-keyword=Right atrial function kn-keyword=Right atrial function en-keyword=Right atrial strain kn-keyword=Right atrial strain en-keyword=Chronic heart failure kn-keyword=Chronic heart failure en-keyword=Echocardiography kn-keyword=Echocardiography END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=1 article-no= start-page=16 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260221 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Compound heterozygosity of a novel missense variant and exonic deletion in hypomyelinating leukodystrophy 15 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hypomyelinating leukodystrophy 15 (HLD15) results from biallelic pathogenic variants in EPRS1, but exonic deletions have not been reported. We describe a 40-year-old woman with mild intellectual disability, ataxia, dystonia, and MRI showing hypomyelination. Whole-exome sequencing identified a heterozygous missense variant in the prolyl-tRNA synthetase domain of EPRS1 (c.3430 C?>?G; p.Leu1144Val, NM_004446.3), without second variant. Whole-genome sequencing revealed a heterozygous 220-bp deletion spanning exon 15 (c.1743-30_1932del), and segregation analysis confirmed compound heterozygosity. RT-PCR from lymphoblastoid cells demonstrated exon-15 skipping leading to a frameshift (p.Asn582Serfs*10) and nonsense-mediated decay, leaving predominant expression of the paternally inherited missense allele. These findings support loss-of-function for the deletion and classify c.3430 C?>?G as likely pathogenic under ACMG/AMP criteria (PM1, PM2, PM3, PP3). This case represents the first exonic deletion reported in EPRS1. The relatively mild, adult-onset phenotype broadens both mutational and clinical spectra of HLD15 and highlights the importance of structural-variant anal en-copyright= kn-copyright= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko 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=OrimoKenta en-aut-sei=Orimo en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UedaKunihiro en-aut-sei=Ueda en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SekiTomonari en-aut-sei=Seki en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShiioYasushi en-aut-sei=Shiio en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= en-aut-name=MoriHarushi en-aut-sei=Mori en-aut-mei=Harushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=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= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology kn-affil= affil-num=5 en-affil=Department of Neurology, Tokyo Teishin Hospital kn-affil= affil-num=6 en-affil=Department of Neurology, Tokyo Teishin Hospital kn-affil= affil-num=7 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Neurology, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Radiology, School of Medicine, Jichi Medical University, kn-affil= affil-num=10 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=11 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology kn-affil= en-keyword=Hypomyelinating leukodystrophy kn-keyword=Hypomyelinating leukodystrophy en-keyword=EPRS1 kn-keyword=EPRS1 en-keyword=Structural variant kn-keyword=Structural variant en-keyword=Exon deletion kn-keyword=Exon deletion en-keyword=Nonsense?mediated decay kn-keyword=Nonsense?mediated decay en-keyword=Whole?genome sequencing kn-keyword=Whole?genome sequencing 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 Fisherfs 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? 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 Childrenfs Hospital kn-affil= affil-num=7 en-affil=Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Childrenfs 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 Childrenfs 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 Childrenfs 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=7 cd-vols= no-issue=2 article-no= start-page=e70170 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=Safety and efficacy of Rez?m water vapour energy therapy in BPH patients receiving antithrombotic therapy: A Japanese single]centre experience en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: The objective of this study is to evaluate the safety and efficacy of Rez?m water vapour energy therapy (WAVE) in Japanese patients with benign prostatic hyperplasia (BPH) continuing antithrombotic therapy and to validate the Okayama University Modified Clavien-Dindo classification (OU-mCD) for perioperative hematuria.
Patients and Methods: We retrospectively analysed 80 consecutive patients who underwent WAVE from August 2023 to July 2024, including 37 (46.2%) continuing antithrombotic therapy perioperatively. Hematuria within 30?days was graded using conventional Clavien-Dindo classification and the OU-mCD, a novel classification focusing on intervention necessity. We assessed clinically significant hematuria (Grade ? Ib), catheter-free rate, prostate volume reduction and haemoglobin change.
Results: Clinically significant hematuria occurred in 21.6% (8/37) of patients continuing antithrombotic therapy versus 4.7% (2/43) without (p?=?0.038). All 10 Grade ? Ib cases occurred during hospitalization with the catheter in place and were managed conservatively with continuous bladder irrigation (median 1 day); none required transfusion or surgical reintervention. Only one patient required temporary drug discontinuation. Treatment efficacy did not differ by antithrombotic status: 86.2% achieved PVR? Conclusion: WAVE can be safely performed with continued antithrombotic therapy. Whereas Grade ?Ib hematuria occurred in 25% of antiplatelet/anticoagulant users (vs. 5% without), 75% had no significant bleeding, and all complications were managed conservatively without transfusion. The OU-mCD provides precise complication stratification. These findings suggest outpatient procedures may be feasible with appropriate patient selection. en-copyright= kn-copyright= en-aut-name=MoriwakeTakatoshi en-aut-sei=Moriwake en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KakuHaruki en-aut-sei=Kaku en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshinagaKasumi en-aut-sei=Yoshinaga en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamanoiTomoaki en-aut-sei=Yamanoi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KatayamaYasuhiro en-aut-sei=Katayama en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= affil-num=1 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Urology, Okamura Isshindo Hospital kn-affil= affil-num=14 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=benign prostatic hyperplasia kn-keyword=benign prostatic hyperplasia en-keyword=hematuriaantithrombotic therapy kn-keyword=hematuriaantithrombotic therapy en-keyword=Japanese kn-keyword=Japanese en-keyword=OU-mCD kn-keyword=OU-mCD en-keyword=water vapour energy therapy kn-keyword=water vapour energy therapy END start-ver=1.4 cd-journal=joma no-vol=88 cd-vols= no-issue=5 article-no= start-page=1003 end-page=1015 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=Claudin-18 expression in gastric type adenocarcinoma and HPV-associated adenocarcinoma of the uterine cervix en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims: Claudin-18 (CLDN18) is both a marker for the gastric phenotype and a therapeutic target. However, little is known about its immunoexpression in endocervical adenocarcinomas (ECAs), particularly as detected using the clone 43-14A antibody, or about the gene expression of its isoforms in ECAs.
Methods and results: We examined CLDN18, HIK1083, p16 and Rb expression by immunohistochemistry and high-risk human papillomavirus (HR-HPV) mRNA by in situ hybridization (ISH) in 121 ECAs, including 35 HPV-independent adenocarcinomas (gastric type [GAS], n?=?24; non-GAS, n?=?11) and 86 HPV-associated ECAs. We also analysed mRNA expression of the CLDN18.1 (lung type) and CLDN18.2 (gastric type) isoforms by quantitative polymerase chain reaction (qPCR) in selected cases. CLDN18 positivity was detected in 8/24 (33%) GASs, 0/11 (0%) non-GASs and 2/86 (2%) HPV-associated ECAs, with positivity defined as staining in ?75% of tumour cells, as in gastric cancer. When a 5% cut-off was used, CLDN18 positivity was detected in 22/24 (92%) GASs, 0/11 (0%) non-GASs and 6/86 (7%) HPV-associated ECAs; CLDN18 expression was thus significantly associated with GAS histology (P? Conclusions: CLDN18 (43-14A) emerged as a potential diagnostic and therapeutic marker for GAS. A minor subset of HPV-associated ECAs also can be immunoreactive for CLDN18 and express CLDN18.2 mRNA, suggesting divergent gastric phenotypic differentiation. The caution is that GAS and HPV-associated ECAs can share overlapping histological features and similar expression of CLDN18 and p16. en-copyright= kn-copyright= en-aut-name=YasutakeNobuko en-aut-sei=Yasutake en-aut-mei=Nobuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokawaYuki en-aut-sei=Yokawa en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=MishimaRiri en-aut-sei=Mishima en-aut-mei=Riri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KomamizuMisato en-aut-sei=Komamizu en-aut-mei=Misato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KugaRyosuke en-aut-sei=Kuga en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=JiromaruRina en-aut-sei=Jiromaru en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawatokoShinichiro en-aut-sei=Kawatoko en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SonodaKenzo en-aut-sei=Sonoda en-aut-mei=Kenzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YahataHideaki en-aut-sei=Yahata en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatoKiyoko en-aut-sei=Kato en-aut-mei=Kiyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OdaYoshinao en-aut-sei=Oda en-aut-mei=Yoshinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=2 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University Fukuoka Japan kn-affil= affil-num=6 en-affil=Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=7 en-affil=Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=8 en-affil=Department of Medicine and Clinical Science, Kyushu University Beppu Hospital kn-affil= affil-num=9 en-affil=Department of Gynecology, Kyushu University Beppu Hospital kn-affil= affil-num=10 en-affil=Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=11 en-affil=Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=12 en-affil=Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=13 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University kn-affil= en-keyword=claudin-18 kn-keyword=claudin-18 en-keyword=endocervical adenocarcinoma kn-keyword=endocervical adenocarcinoma en-keyword=gastric type kn-keyword=gastric type en-keyword=human papillomavirus kn-keyword=human papillomavirus en-keyword=p16 kn-keyword=p16 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=20260225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical and Genetic Landscape of Glioblastoma, IDH-Wildtype With FGFR Gene Family Alterations en-subtitle= kn-subtitle= en-abstract= kn-abstract=Glioblastoma, isocitrate dehydrogenase wildtype (GBM, IDH-wt), is a highly aggressive brain tumor with a poor prognosis. Alterations in the fibroblast growth factor receptor (FGFR) gene family?such as FGFR::TACC fusions and FGFR1 mutations?have emerged as potential therapeutic targets; however, their clinical and genetic features in GBM, IDH-wt remain unclear. We analyzed 1076 GBM, IDH-wt cases using comprehensive genomic profiling data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan. FGFR alterations were detected in 8.0% of patients, including FGFR::TACC fusions (3.3%) and FGFR1 mutations (2.9%). The FGFR::TACC fusion-positive group was older at diagnosis and showed higher frequencies of TERT promoter mutation and MDM2 amplification, and lower frequencies of EGFR amplification and TP53 mutation, compared with the fusion-negative group. The FGFR1 mutation-positive group was enriched for ATRX, NF1, and PIK3CA mutations and had significantly fewer TERT promoter and PTEN mutations, compared with the mutation-negative group. No significant differences in overall survival were observed, although both groups tended to have longer median overall survival compared with their respective negative groups. This study represents the largest genomic cohort to date of FGFR alterations in GBM, IDH-wt. FGFR::TACC fusion-positive and FGFR1 mutation-positive GBMs exhibited distinct genetic profiles, highlighting the clinical relevance of molecular subclassification and providing insight for future therapeutic strategies. en-copyright= kn-copyright= en-aut-name=KegoyaYasuhito en-aut-sei=Kegoya en-aut-mei=Yasuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=MizutaRyo en-aut-sei=Mizuta en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IkemachiRyosuke en-aut-sei=Ikemachi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamiuraMako en-aut-sei=Kamiura en-aut-mei=Mako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=9 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=10 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=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=copy number alteration kn-keyword=copy number alteration en-keyword=FGFR kn-keyword=FGFR en-keyword=glioblastoma kn-keyword=glioblastoma en-keyword=single-nucleotide variant kn-keyword=single-nucleotide variant END start-ver=1.4 cd-journal=joma no-vol=191 cd-vols= no-issue= article-no= start-page=1 end-page=16 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=A Consideration on Roles and Issues of Universities in Developing Teachers and Staff Training: Through the Activities of Okayama University Center for NITS kn-title=EC̍xɉʂw̖Ɖۑ \ NITS RwZ^[̊ʂ \ en-subtitle= kn-subtitle= en-abstract= kn-abstract=@{_ł́CEƂĂ̋E̊wтۏႷ錤ĈCƂɑwʂƉۑɂ‚čl@BE̊wт͋ψł̌CCΖZł̌CCEw@ł̊wCCĉł̌CȂǂɂēWJBwJE{錤C͂Ƃǂ֘ACǂ̂悤ȓF‚BƗs@lEx@\iȉCNITSjRwZ^[̊ʂČBāCw͋E̊wт̃j[Yɉ鑤ɂ邾łȂCE̊wтč\CIIȊwтxEiĂƂĂ̖ʂ̂ł邱Ƃl@B܂CwAEgJďCJ̕KvwEC̎g̉ۑƂĎB en-copyright= kn-copyright= en-aut-name=TAKASEAtsushi en-aut-sei=TAKASE en-aut-mei=Atsushi kn-aut-name=~ kn-aut-sei= kn-aut-mei=~ aut-affil-num=1 ORCID= en-aut-name=TSURUMIAkiko en-aut-sei=TSURUMI en-aut-mei=Akiko kn-aut-name=ߊCq kn-aut-sei=ߊC kn-aut-mei=q aut-affil-num=2 ORCID= en-aut-name=KUROSUMIChiyo en-aut-sei=KUROSUMI en-aut-mei=Chiyo kn-aut-name=Zm kn-aut-sei=Z kn-aut-mei=m aut-affil-num=3 ORCID= en-aut-name=KIYOTATetsuo en-aut-sei=KIYOTA en-aut-mei=Tetsuo kn-aut-name=cNj kn-aut-sei=c kn-aut-mei=Nj aut-affil-num=4 ORCID= en-aut-name=INADAYoshihiko en-aut-sei=INADA en-aut-mei=Yoshihiko kn-aut-name=cF kn-aut-sei=c kn-aut-mei=F aut-affil-num=5 ORCID= en-aut-name=MATSUURAAi en-aut-sei=MATSUURA en-aut-mei=Ai kn-aut-name=Y kn-aut-sei=Y kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MIYAMOTOKouji en-aut-sei=MIYAMOTO en-aut-mei=Kouji kn-aut-name={{_ kn-aut-sei={{ kn-aut-mei=_ aut-affil-num=7 ORCID= en-aut-name=MATSUEDAMutsumi en-aut-sei=MATSUEDA en-aut-mei=Mutsumi kn-aut-name=}r kn-aut-sei=} kn-aut-mei=r aut-affil-num=8 ORCID= en-aut-name=TSUSHIMAAiko en-aut-sei=TSUSHIMA en-aut-mei=Aiko kn-aut-name=Óq kn-aut-sei=Ó kn-aut-mei=q aut-affil-num=9 ORCID= en-aut-name=MIYAZAKIYoshio en-aut-sei=MIYAZAKI en-aut-mei=Yoshio kn-aut-name={PY kn-aut-sei={ kn-aut-mei=PY aut-affil-num=10 ORCID= en-aut-name=TAKEMOTOToshiya en-aut-sei=TAKEMOTO en-aut-mei=Toshiya kn-aut-name=|{r kn-aut-sei=|{ kn-aut-mei=r aut-affil-num=11 ORCID= en-aut-name=SAWATANIYoko en-aut-sei=SAWATANI en-aut-mei=Yoko kn-aut-name=VJzq kn-aut-sei=VJ kn-aut-mei=zq aut-affil-num=12 ORCID= en-aut-name=KAJIIKazuaki en-aut-sei=KAJII en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KANAGAWAMakiko en-aut-sei=KANAGAWA en-aut-mei=Makiko kn-aut-name=앑Mq kn-aut-sei= kn-aut-mei=Mq aut-affil-num=14 ORCID= affil-num=1 en-affil=Faculty of Education, Okayama University kn-affil=Rwwp@w affil-num=2 en-affil=Okayama University Kindergarten kn-affil=Rwct affil-num=3 en-affil=Okayama University Kindergarten kn-affil=Rwct affil-num=4 en-affil=Faculty of Education, Okayama University kn-affil=Rwwp@w affil-num=5 en-affil=Faculty of Education, Okayama University kn-affil=Rwwp@w affil-num=6 en-affil=Faculty of Education, Okayama University kn-affil=Rwwp@w affil-num=7 en-affil=Faculty of Education, Okayama University kn-affil=Rwwp@w affil-num=8 en-affil=Faculty of Education, Okayama University kn-affil=Rwwp@w affil-num=9 en-affil=Faculty of Education, Okayama University kn-affil=Rwwp@w affil-num=10 en-affil=Faculty of Education, Okayama University kn-affil=Rwwp@w affil-num=11 en-affil=Okayama University School for Special Needs Education kn-affil=RwʎxwZ affil-num=12 en-affil=Okayama University School for Special Needs Education kn-affil=RwʎxwZ affil-num=13 en-affil=Faculty of Education, Okayama University kn-affil=Rwwp@w affil-num=14 en-affil=Faculty of Education, Okayama University kn-affil=Rwwp@w en-keyword=EC kn-keyword=EC en-keyword=x kn-keyword=x en-keyword=w kn-keyword=w en-keyword=NITS kn-keyword=NITS en-keyword=EƂĂ̋E kn-keyword=EƂĂ̋E END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=e70154 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260217 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mitrofanoff Appendicovesicostomy With Boari Flap for Complete Female Urethral Transection: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Female urethral complete transection caused by pelvic trauma is extremely rare, and no standard management has been established when urethral reconstruction is not feasible.
Case Presentation: A woman in her twenties sustained an open pelvic fracture with perineal injury due to a traffic accident. Complete urethral transection was identified, and a suprapubic cystostomy was placed. After staged vaginal reconstruction and bladder function evaluation, a Mitrofanoff appendicovesicostomy was performed. Because the appendix was not enough to reach the umbilicus, a Boari flap was created to compensate for the length. Urodynamic evaluation showed improvement from a preoperative high-pressure bladder to increased compliance postoperatively, though pharmacological management was still required. Postoperatively, the patient achieved stable clean intermittent catheterization without complications.
Conclusion: The Mitrofanoff procedure can be an effective option in female urethral injuries where reconstruction is impossible. The addition of a Boari flap may expand its applicability by overcoming conduit length limitations. en-copyright= kn-copyright= en-aut-name=MoriKohei en-aut-sei=Mori en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamasakiYuichiro en-aut-sei=Yamasaki en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Kanagawa Children's Medical Center kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Boari flap kn-keyword=Boari flap en-keyword=female urethral transection kn-keyword=female urethral transection en-keyword=Mitrofanoff kn-keyword=Mitrofanoff 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= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260219 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tabtoxin biosynthetic gene cluster in Pseudomonas syringae pv. tabaci 6605 genomic island 1 (GI-1Pta6605) is required for severe disease symptoms en-subtitle= kn-subtitle= en-abstract= kn-abstract=One of the genomic islands in Pseudomonas syringae pv. tabaci 6605 (GI-1Pta6605) has been identified as a pathogenicity island required for virulence because the deletion almost completely eliminated disease symptoms in inoculation tests at 4?~?105 CFU/ml. GI-1Pta6605 contains four cargo regions (CRs) named CR-1 to CR-4. The ?CR-4 mutant did not produce tabtoxin like ?GI-1 and disease symptoms did not develop in tobacco. However, it grew, although to a lesser extent than the wild-type strain. These results indicate that the tabtoxin biosynthetic gene cluster in GI-1 is required for virulence but not for establishment of compatibility. en-copyright= kn-copyright= en-aut-name=KunishiKotomi en-aut-sei=Kunishi en-aut-mei=Kotomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujisawaNorika en-aut-sei=Fujisawa en-aut-mei=Norika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=5 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=6 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=7 ORCID= affil-num=1 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=GI-1Pta6605 kn-keyword=GI-1Pta6605 en-keyword=Pathogenicity island kn-keyword=Pathogenicity island en-keyword=Pseudomonas syringae kn-keyword=Pseudomonas syringae en-keyword=Tabtoxin kn-keyword=Tabtoxin END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=16 article-no= start-page=9663 end-page=9677 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251011 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of sulfation for cellulose pulp to change its fiber morphology and appearance to transparent in water en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cellulose pulp (CP) is composed mainly of cellulose which is one of the most useful and sustainable natural polymers. Cellulose-based materials, such as completely dispersed nanofibers and water-soluble cellulose, are transparent in water. Additionally, chemical modification of CP has been employed as a pretreatment for the preparation of nanofibers and to impart absorption properties derived from anionic functional groups. However, little is known about chemically modified CPs comprising micron-scale fibers that are transparent in water.In this study, we synthesized transparent sulfated cellulose pulp (TSCP) that exhibits good dispersion stability, high transparency in water, and highly swollen fiber structures. The sulfation method involved heating sulfamic acid and urea supported on CP. TSCP synthesized using a sulfamic acid amount relative to CP (Q) of 18.5, a molar ratio of urea to sulfamic acid (R) of 0.80, and a reaction temperature of 140 C exhibited the highest total light transmittance (94.7%) in water, a degree of polymerization (535), and amount of sulfate groups (1.73 mmol/g). Polarization microscopy confirmed that most TSCP fibers swelled in water along the fiber width direction. The structure of hydrous-state TSCP was further confirmed using low-vacuum scanning electron microscopy. The maximum fiber width of the swollen TSCP reached 122 m, which was approximately six times than that of CP. The crystallinity was equivalent to that of the original CP with a Cellulose I-type crystalline structure. This transparent, hydrous-state TSCP, comprising predominantly swollen CP fibers, demonstrates potential for applications as a transparent material. en-copyright= kn-copyright= en-aut-name=NishimuraAyato en-aut-sei=Nishimura en-aut-mei=Ayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaTetsuya en-aut-sei=Uchida en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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= en-keyword=Cellulose pulp kn-keyword=Cellulose pulp en-keyword=Sulfation kn-keyword=Sulfation en-keyword=Transparent kn-keyword=Transparent en-keyword=Swollen fiber structure kn-keyword=Swollen fiber structure en-keyword=Microscopy kn-keyword=Microscopy en-keyword=Refractive index kn-keyword=Refractive index END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=1 article-no= start-page=pgaf393 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=Chloroplast heat shock protein cpHsc70-1 interacts with thylakoid membrane remodeling protein VIPP1 C-terminal tail and controls VIPP1 oligomer assembly en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oxygenic photosynthetic organisms depend on the thylakoid membranes (TMs) for light-driven energy conversion. Recent studies on TM homeostasis (thylakostasis) have highlighted the essential role of the TM remodeling protein vesicle-inducing protein in plastid 1 (VIPP1). As a member of the endosomal sorting complexes required for transport-III (ESCRT-III)/phage shock protein A (PspA)/VIPP1 superfamily, VIPP1 forms large ring- and filament-like homo-oligomeric structures that exhibit a membrane remodeling activity. The oligomerization status was proposed to be modulated by the intrinsically disordered C-terminal tail (Vc), whereas its functional role remained unclear. Notably, this Vc region is conserved not only in photosynthetic VIPP1 but also in the PspA proteins of extremophilic species, implicating its role in membrane stress responses. To investigate the role of the Vc region in VIPP1 assembly, we performed coimmunoprecipitation assays in Arabidopsis chloroplasts and identified chloroplast-localized HSP70 proteins (cpHsc70) as major interactors. Among the two isoforms, cpHsc70-1 was found to be specifically required for modulating VIPP1 oligomeric assembly and dynamics in response to heat stress. Genetic analyses revealed that cpHsc70-1 facilitates the disassembly of VIPP1 oligomers, similarly to Vps4 ATPase in ESCRT-III; loss of either the Vc region or cpHsc70-1-impaired VIPP1 disassembly, resulting in more static oligomeric structures. Furthermore, cpHsc70-1 exhibited a broader role in chloroplast proteostasis, as the cphsc70-1 mutant showed impaired accumulation of green fluorescent protein (GFP)-fusion proteins. Together, our findings uncover a crucial crosstalk between proteostasis and thylakostasis in chloroplasts, coordinated by cpHsc70-1 and VIPP1 in response to membrane stress. en-copyright= kn-copyright= en-aut-name=LiDi en-aut-sei=Li en-aut-mei=Di kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GachieSarah Wanjiru en-aut-sei=Gachie en-aut-mei=Sarah Wanjiru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=ScholzMartin en-aut-sei=Scholz en-aut-mei=Martin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HipplerMichael en-aut-sei=Hippler en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakamotoWataru en-aut-sei=Sakamoto en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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= affil-num=4 en-affil=Institute of Plant Biology and Biotechnology, University of M?nster kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Arabidopsis thaliana kn-keyword=Arabidopsis thaliana en-keyword=chloroplast kn-keyword=chloroplast en-keyword=heat shock protein kn-keyword=heat shock protein en-keyword=photosynthesis kn-keyword=photosynthesis en-keyword=thylakoid membrane remodeling kn-keyword=thylakoid membrane remodeling END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=4591 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Calcium ions play a critical role in calcification of Corynebacterium matruchotii en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dental calculus is a hardened deposit composed of calcium phosphate precipitated within dental plaque. While the involvement of dental calculus in the progression of periodontal disease is well established, many aspects of its formation process remain poorly understood. In this study, we focused on Corynebacterium matruchotii, a key bacterium involved in dental calculus formation, and investigated the role of calcium ions in calcification, as well as the associated internal and external changes in the bacterium through long-term observation. In the absence of calcium ions, no intracellular calcification was observed, and the lipid bilayer with the formation of holes in bacterial body was evident. In contrast, in the presence of calcium ions, lipid bilayer remained intact, and intracellular needle- and plate- like crystals were formed. Furthermore, calcified C. matruchotii showed increased flocculation compared to non-calcified C. matruchotii. These results indicate that the influx of calcium ions is essential for intracellular calcification. Calcium ions entry appears to reinforce the integrity of the lipid bilayer, providing a stable intracellular environment conductive to calcification. Moreover, calcified C. matruchotii may contribute to the nucleation of dental calculus by forming aggregates composed of both bacterial components and calcified material. en-copyright= kn-copyright= en-aut-name=OharaNaoko en-aut-sei=Ohara en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgawaMidori en-aut-sei=Ogawa en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakebeKatsuki en-aut-sei=Takebe en-aut-mei=Katsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TosaIkue en-aut-sei=Tosa en-aut-mei=Ikue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OnoSerina en-aut-sei=Ono en-aut-mei=Serina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SaitoMitsumasa en-aut-sei=Saito en-aut-mei=Mitsumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Microbiology, School of Medicine, University of Occupational and Environmental Health kn-affil= affil-num=3 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Microbiology, School of Medicine, University of Occupational and Environmental Health kn-affil= affil-num=7 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Calcification kn-keyword=Calcification en-keyword=Corynebacterium matruchotii kn-keyword=Corynebacterium matruchotii en-keyword=Dental calculus kn-keyword=Dental calculus en-keyword=Calcium ions kn-keyword=Calcium ions 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? 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=22 cd-vols= no-issue=1 article-no= start-page=98 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260119 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genetic and phenotypic identities of Staphylococcus coagulans isolated from pustules of dogs with superficial bacterial folliculitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Staphylococcus coagulans, formerly called Staphylococcus schleiferi subsp. coagulans is the second most common isolate from skin lesions of dogs with superficial bacterial folliculitis (SBF). However, the clinical significance of S. coagulans in pustules of canine SBF remains uncertain. This study aimed to investigate the prevalence and genotypic and phenotypic diversity of S. coagulans isolated from pustules in two dogs with SBF.
Results Two dogs with SBF were included in this study. S. schleiferi/coagulans was isolated as the sole organism from three pustules in case #1, whereas it coexisted with S. pseudintermedius in two of seven pustules in case #2. S. pseudintermedius was the sole organism in the remaining five pustules in case #2. Whole genome sequences revealed that all isolates tested were annotated as S. coagulans. The isolates from the same pustules exhibited identical genotypic and phenotypic profiles, indicating clonal multiplication. S. coagulans isolated from different pustules exhibited similar yet distinct genotypic and phenotypic profiles.
Conclusions S. coagulans with identical genetic and phenotypic profiles can be identified as the sole pathogen or coexist with S. pseudintermedius in the pustules of the same dogs with SBF. en-copyright= kn-copyright= en-aut-name=OsumiTakafumi en-aut-sei=Osumi en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShinomiyaYuuki en-aut-sei=Shinomiya en-aut-mei=Yuuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WanganuttaraThamonwan en-aut-sei=Wanganuttara en-aut-mei=Thamonwan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImanishiIchiro en-aut-sei=Imanishi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimazakiYotaro en-aut-sei=Shimazaki en-aut-mei=Yotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IyoriKeita en-aut-sei=Iyori en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyodaYoichi en-aut-sei=Toyoda en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IdeKaori en-aut-sei=Ide en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=NishifujiKoji en-aut-sei=Nishifuji en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology kn-affil= affil-num=2 en-affil=Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology kn-affil= affil-num=3 en-affil=Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=5 en-affil=Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology kn-affil= affil-num=6 en-affil=1sec Co. Ltd. kn-affil= affil-num=7 en-affil=1sec Co. Ltd. kn-affil= affil-num=8 en-affil=Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology kn-affil= affil-num=9 en-affil=Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology kn-affil= en-keyword=Staphylococcus coagulans kn-keyword=Staphylococcus coagulans en-keyword=Staphylococcus pseudintermedius kn-keyword=Staphylococcus pseudintermedius en-keyword=Dog kn-keyword=Dog en-keyword=Superficial bacterial folliculitis kn-keyword=Superficial bacterial folliculitis en-keyword=Antimicrobial susceptibility kn-keyword=Antimicrobial susceptibility en-keyword=Disk diffusion test kn-keyword=Disk diffusion test 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=16 cd-vols= no-issue= article-no= start-page=1716939 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=Structural analysis of PSI-ACPI and PSII-ACPII supercomplexes from a cryptophyte alga Rhodomonas sp. NIES-2332 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Light energy is converted to chemical energy by two photosystems (PSI and PSII) in complex with their light-harvesting complex proteins (LHCI and LHCII) in photosynthesis. Rhodomonas is a member of cryptophyte alga whose LHCs contain unique chlorophyll a/c proteins (ACPs) and phycobiliproteins. We purified PSI-ACPI and PSII-ACPII supercomplexes from a cryptophyte Rhodomonas sp. NIES-2332 and analyzed their structures at high resolutions of 2.08 ? and 2.17 ?, respectively, using cryo-electron microscopy. These structures are largely similar to those reported previously from two other species of cryptophytes, but exhibited some differences in both the pigment locations and subunit structures. A part of the antenna subunits of both photosystems is shifted compared with the previously reported structures from other species of cryptophytes, suggesting some differences in the energy transfer rates from the antenna to the PSI and PSII cores. Newly identified lipids are found to occupy the interfaces between the antennae and cores, which may be important for assembly and stabilization of the supercomplexes. Water molecules surrounding three iron-sulfur clusters of the PSI core are found in our high-resolution structure, some of which are conserved from cyanobacteria to higher plants but some are different. In addition, our structure of PSII-ACPII lacks the subunits of oxygen-evolving complex as well as the Mn4CaO5 cluster, suggesting that the cells are in the S-growth phase, yet the PSI-ACPI structure showed the binding of PsaQ, suggesting that it is in an L-phase. These results suggest that the S-phase and L-phase can co-exist in the cryptophytic cells. The high-resolution structures of both PSI-ACPIs and PSII-ACPIIs solved in this study provide a more solid structural basis for elucidating the energy transfer and quenching mechanisms in this group of the organisms. en-copyright= kn-copyright= en-aut-name=ZhangWenyue en-aut-sei=Zhang en-aut-mei=Wenyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoneharaNozomi en-aut-sei=Yonehara en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshiiMizuki en-aut-sei=Ishii en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=JiangHaowei en-aut-sei=Jiang en-aut-mei=Haowei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=La RoccaRomain en-aut-sei=La Rocca en-aut-mei=Romain kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsaiPi-Cheng en-aut-sei=Tsai en-aut-mei=Pi-Cheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LiHongjie en-aut-sei=Li en-aut-mei=Hongjie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AkitaFusamichi en-aut-sei=Akita en-aut-mei=Fusamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= affil-num=1 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=cryptophytes kn-keyword=cryptophytes en-keyword=Rhodomonas kn-keyword=Rhodomonas en-keyword=photosystem I kn-keyword=photosystem I en-keyword=photosystem II kn-keyword=photosystem II en-keyword=light-harvesting complex kn-keyword=light-harvesting complex en-keyword=photosynthesis kn-keyword=photosynthesis END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=13 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pan-cancer profiling links C1orf50 to DNA repair and immune modulation in ovarian cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background C1orf50 encodes a small, evolutionarily conserved protein, the function of which remains unclear. Its significance across various human cancers, particularly its specific role in ovarian cancer within an immunogenomic context, is not yet fully understood. Utilizing The Cancer Genome Atlas and single-cell RNA sequencing (scRNA-seq) public datasets, we conducted a comprehensive profiling of C1orf50 across multiple cancer types, with a particular focus on ovarian cancer, to investigate its associations with copy-number status, genomic instability, tumor programs, and the immune microenvironment.
Results Across cancer types, copy-number gain or amplification of C1orf50 was most frequent in ovarian cancer and closely tracked with higher messenger RNA levels. Higher C1orf50 expression was associated with a greater tumor mutational burden and homologous recombination deficiency, as indicated by gene-set patterns that suggested heightened cell-cycle and cellular stress responses accompanied by reduced oxidative phosphorylation, enrichment of regulatory T cells, and depletion of resting memory CD4 T cells. In ovarian cancer, focal events at chromosome 1p34.2 were accompanied by stepwise increases in C1orf50 expression by clinical stage and were linked to higher tumor mutational burden, homologous recombination deficiency, and greater loss of heterozygosity, together with more frequent gene alterations in BRCA1 or BRCA2. Immune composition clustered into profiles consistent with an immunosuppressive context in tumors with higher C1orf50 expression. The scRNA-seq data further revealed that cancer cells enhanced immune-suppressive interactions with various immune cell populations and diminished antigen-presentation signals. Analyses of genomic instability in ovarian cancer suggested mutational processes compatible with base-substitution patterns associated with cytidine deaminase activity and with insertion-deletion patterns characteristic of homologous recombination failure, while transcript-level patterns pointed to a broad downshift of canonical DNA repair activity with apparent compensatory adjustments in related pathways rather than a uniform change in any single pathway.
Conclusions The overexpression of C1orf50 characterizes an aggressive immunogenomic phenotype in ovarian cancer, distinguished by genomic instability, impaired DNA repair mechanisms, and extensive immunosuppression. These findings indicate that C1orf50 warrants consideration as a potential biomarker and a prospective target for therapeutic investigation. Furthermore, they advocate for the progression to prospective validation and functional studies to ascertain its clinical significance. en-copyright= kn-copyright= en-aut-name=RogachevskayaAnna en-aut-sei=Rogachevskaya en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaniYusuke en-aut-sei=Otani en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhtsuAkira en-aut-sei=Ohtsu en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChinVanessa D. en-aut-sei=Chin en-aut-mei=Vanessa D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Pe?aTirso en-aut-sei=Pe?a en-aut-mei=Tirso kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AraiSeiji en-aut-sei=Arai en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaAtsushi en-aut-sei=Tanaka en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Harvard Medical School kn-affil= affil-num=4 en-affil=UMass Chan Medical School, UMass Memorial Medical Center kn-affil= affil-num=5 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=6 en-affil=Department of Urology, Gunma University Graduate School of Medicine 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 kn-affil= affil-num=8 en-affil=Department of Molecular Physiology, Faculty of Medicine, Graduate School of Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= en-keyword=C1orf50 kn-keyword=C1orf50 en-keyword=Pan-cancer analysis kn-keyword=Pan-cancer analysis en-keyword=DNA repair kn-keyword=DNA repair en-keyword=Gene expression kn-keyword=Gene expression en-keyword=Tumor microenvironment kn-keyword=Tumor microenvironment en-keyword=Immune evasion kn-keyword=Immune evasion en-keyword=Single-cell RNA-seq kn-keyword=Single-cell RNA-seq 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? 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 Childrenfs Medical Center kn-affil= affil-num=7 en-affil=Division of Infectious Diseases and Immunology, Saitama Childrenfs 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=76 cd-vols= no-issue=1 article-no= start-page=100065 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=Effects of systemic ventricular assist combined with fenestration in failing Fontan: A theoretical analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Biventricular assist for failing Fontan circulation remains challenging. Because fenestration effectively reduces stressed blood volume and central venous pressure in Fontan patients with increased pulmonary vascular resistance (PVR), systemic ventricular assist device (VAD) combined with fenestration may improve hemodynamics in failing Fontan patients with increased PVR who would require biventricular assist. To validate this hypothesis, we performed a computational hemodynamic simulation of the failing Fontan circulation using a lumped parameter model. We compared hemodynamic variables between the models with and without fenestration while the PVR index was increased sequentially from 3.01 to 6.81 Wood Units m2. Following VAD initiation and stressed blood volume reduction, central venous pressure was maintained at a lower level in the fenestration models. This positive effect was greater in the model with larger fenestration diameter. However, excessive fenestration caused significant desaturation. In failing Fontan circulation with elevated PVR, systemic VAD combined with fenestration significantly improved hemodynamics. en-copyright= kn-copyright= en-aut-name=ShimizuShuji en-aut-sei=Shimizu en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KotaniYasuhiro en-aut-sei=Kotani en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HorioNaohiro en-aut-sei=Horio en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KisamoriEiri en-aut-sei=Kisamori en-aut-mei=Eiri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyaharaYoshinori en-aut-sei=Miyahara en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UemuraKoji en-aut-sei=Uemura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShishidoToshiaki en-aut-sei=Shishido en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KasaharaShingo en-aut-sei=Kasahara en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=5 en-affil=Pediatric Heart Disease and Adult Congenital Heart Disease Center, Showa Medical University Hospital kn-affil= affil-num=6 en-affil=Department of Research Promotion and Management, National Cerebral and Cardiovascular Center kn-affil= affil-num=7 en-affil=Department of Research Promotion and Management, National Cerebral and Cardiovascular Center kn-affil= affil-num=8 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= en-keyword=Fontan circulation kn-keyword=Fontan circulation en-keyword=Hemodynamic simulation kn-keyword=Hemodynamic simulation en-keyword=Ventricular assist device kn-keyword=Ventricular assist device en-keyword=Fenestration kn-keyword=Fenestration en-keyword=Pulmonary vascular resistance kn-keyword=Pulmonary vascular resistance 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 teachersf 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 teachersf 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 teachersf 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=FielfardhKhalifatulloh en-aut-sei=Fielfardh 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=32 cd-vols= no-issue=12 article-no= start-page=8903 end-page=8905 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250818 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mesenteric Route Superior Mesenteric Artery First Approach in Robot-Assisted Pancreatoduodenectomy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background. The superior mesenteric artery (SMA) approach is crucial for the successful implementation of robot-assisted pancreatoduodenectomy (RPD). Herein, we present a novel technique, the mesenteric route SMA-first approach, for RPD.
Patients and Methods. A 20-year-old woman with a 50 mm intraductal papillary mucinous neoplasm underwent RPD. As the tumor was large and located close to the mesenteric vessels, we developed the mesenteric route SMA-first approach.
Results. Following the mesenteric Kocher maneuver, the mesenteric route SMA-first approach was applied. With appropriate retraction of the pancreatic head, dissection around the mesenteric vessels was performed and their branches were divided. The uncinate process dissection (PL, ph II) was performed via the mesenteric route. This approach facilitated dorsal dissection, particularly around the large tumor. After dissection of the hepatoduodenal ligament, the remaining pancreatic nerve plexus (PL ph I) was dissected. Finally, the pancreas was divided on the superior mesenteric vein, and the specimen was resected. Operative time was 390 min with minimal blood loss.
Conclusions. The mesenteric route SMA-first approach enables uncinate process dissection via the mesenteric route. This technique may be a safe and feasible option for selected patients, such as nonobese individuals with a large pancreatic head tumor near major vessels. en-copyright= kn-copyright= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoAtene en-aut-sei=Ito en-aut-mei=Atene kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiyamaTakeyoshi en-aut-sei=Nishiyama en-aut-mei=Takeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YanagiharaTsubasa en-aut-sei=Yanagihara en-aut-mei=Tsubasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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= en-keyword=Robotic pancreaticoduodenectomy kn-keyword=Robotic pancreaticoduodenectomy en-keyword=Superior mesenteric artery approach kn-keyword=Superior mesenteric artery approach en-keyword=Mesenteric route kn-keyword=Mesenteric route END start-ver=1.4 cd-journal=joma no-vol=410 cd-vols= no-issue=1 article-no= start-page=171 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Robotic distal pancreatectomy using two-surgeon technique (TAKUMI-4): a technical note and initial outcomes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose With the increasing use of minimally invasive distal pancreatectomy, the use of robotic distal pancreatectomy (RDP) is also increasing worldwide. Standardized surgical protocols are essential for safe implementation of RDP. In this study, we present our surgical protocol and initial outcomes of RDP using gtwo-surgeon techniqueh.
Methods Our standard RDP protocol included a two-surgeon technique for cooperation, rationality, and education. Short-term outcomes of RDP were also investigated. This retrospective study included 77 consecutive patients who underwent RDP at our institution between April 2021 and January 2025.
Results The median operative time, estimated blood loss, and postoperative hospital stay were 214 min (interquartile range [IQR], 176?253), 10 mL (IQR, 0?50), and 9 days (IQR, 8?10), respectively. A textbook outcome was achieved in 84.4% of patients. Moreover, superior outcomes of RDP (n?=?77) compared with those of laparoscopic distal pancreatectomy (n?=?62) were confirmed in this study.
Conclusion Using the two-surgeon technique, we successfully standardized and introduced the RDP program. The two-surgeon technique can contribute to the safe introduction of RDP and expansion of the program. en-copyright= kn-copyright= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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= en-keyword=Distal pancreatectomy kn-keyword=Distal pancreatectomy en-keyword=Robotic surgery: minimally invasive surgery kn-keyword=Robotic surgery: minimally invasive surgery en-keyword=Training kn-keyword=Training en-keyword=Outcomes kn-keyword=Outcomes END start-ver=1.4 cd-journal=joma no-vol=39 cd-vols= no-issue=5 article-no= start-page=3137 end-page=3145 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of visceral fat area on surgical difficulty during robotic distal pancreatectomy (TAKUMI-2) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Difficulty scoring systems (DSS) have been developed to quantify the surgical complexity of laparoscopic distal pancreatectomy (LDP). However, few studies have validated these systems in the context of robotic distal pancreatectomy (RDP). Moreover, the impact of body composition on RDP outcomes remains unexplored. This study aimed to investigate the risk factors of surgical difficulty in RDP, including body composition.
Methods: This retrospective study included 72 consecutive patients who underwent RDP at our institution between April 2021 and October 2024. Using a modified DSS for LDP, patients were divided into three difficulty index groups. The association between the difficulty index and outcomes was investigated. Multivariate analyses were performed to identify risk factors associated with surgical difficulty (prolonged operative time) in RDP.
Results: Patients were classified into three difficulty index groups: low (n?=?28), intermediate (n?=?25), and high (n?=?19). Operative time was significantly associated with the surgical index (P?=?0.01). Moreover, visceral fat area (VFA) was significantly correlated with operative time (r2?=?0.10, P?=?0.008). The multivariate analyses found that VFA (??100 cm2) (odds ratio [OR] 5.03, 95% confidence interval [CI] 1.32?22.4, P?=?0.02), malignancy (OR 4.92, 95% CI 1.50?18.9, P?=?0.01), and pancreatic resection on the portal vein (OR 4.14, 95% CI 1.24?15.9, P?=?0.02) were significant risk factors associated with surgical difficulty.
Conclusion: VFA could be a novel and useful factor for assessing the surgical difficulty associated with RDP. en-copyright= kn-copyright= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaMotohiko en-aut-sei=Yamada en-aut-mei=Motohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiyamaTakeyoshi en-aut-sei=Nishiyama en-aut-mei=Takeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KanehiraNoriyuki en-aut-sei=Kanehira en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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= en-keyword=Robotic distal pancreatectomy kn-keyword=Robotic distal pancreatectomy en-keyword=Difficulty score kn-keyword=Difficulty score en-keyword=Visceral fat area kn-keyword=Visceral fat area END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=e70069 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=Metachronous Pancreatic Metastasis of Myxoid Liposarcoma Successfully Treated With Robotic Spleen]Preserving Distal Pancreatectomy With Splenic Vessels Resections: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pancreatic metastasis of myxoid liposarcoma (MLS) after primary resection is extremely rare. Herein, we present a case of metachronous pancreatic metastasis of MLS that was successfully treated with robotic spleen-preserving distal pancreatectomy (SPDP) using the Warshaw technique. A 60-year-old woman underwent radical resection of a 25-cm MLS in the right thigh after receiving neoadjuvant radiotherapy. The patient developed a 6-cm solitary pancreatic metastasis of the MLS 2?years later. Because no other distant metastases were detected, robotic SPDP (Warshaw technique) was performed. The operative time was 140?min with minimal blood loss. Follow-up at 3?months showed no recurrence. To our knowledge, this is the first report of a case of metachronous pancreatic metastasis of MLS successfully treated with robotic SPDP. Curative resection using minimally invasive surgery should be performed for solitary pancreatic metastases from MLS. en-copyright= kn-copyright= en-aut-name=SotaYumi en-aut-sei=Sota en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaMotohiko en-aut-sei=Yamada en-aut-mei=Motohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiyamaTakeyoshi en-aut-sei=Nishiyama en-aut-mei=Takeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanehiraNoriyuki en-aut-sei=Kanehira en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MasunagaAkari en-aut-sei=Masunaga en-aut-mei=Akari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=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 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= en-keyword=myxoid liposarcoma kn-keyword=myxoid liposarcoma en-keyword=pancreatic metastasis kn-keyword=pancreatic metastasis en-keyword=robotic surgery kn-keyword=robotic surgery END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=7 article-no= start-page=1259 end-page=1267 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=How to report and discuss subgroup analyses in clinical practice guidelines? Evaluation procedure of the clinical and statistical relevancy en-subtitle= kn-subtitle= en-abstract= kn-abstract=The results of subgroup analyses of clinical trials are important reference information when considering the generalizability of a study treatment, i.e., providing the best treatment for each individual patient. The results of subgroup analyses are often presented in publications, etc. as forest plots focusing on patient backgrounds. However, it is important to fully understand and grasp some of the issues involved in subgroup analyses and to interpret the results carefully to apply them in clinical practice. Although the literature includes some reports on how subgroup analyses should be evaluated and handled for the purpose of establishing medical practice guidelines, most of the papers have mainly evaluated the reliability of subgroup analyses from a statistical perspective; few of them have incorporated clinical importance in their evaluations. Therefore, in December 2019, we established a Subgroup Analysis Review Committee consisting of oncologists specializing in lung cancer treatment and statistical experts among the members of the Guidelines Review Committee of the Japanese Lung Cancer Association, with the aim of appropriately reflecting subgroup analysis in Japanese lung cancer practice guidelines. We developed a new evaluation strategy to incorporate clinical aspects as well as reliability assessment. Specifically, on the basis of a clinical and statistical review of the problems with subgroup analyses presented as clinical trial results, we developed criteria and procedures to ensure consistency and fairness in the citation of clinical guidelines. en-copyright= kn-copyright= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiuraSatoru en-aut-sei=Miura en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OyaYuko en-aut-sei=Oya en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoTomohiro en-aut-sei=Sakamoto en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaKentaro en-aut-sei=Tanaka en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TeraokaShunsuke en-aut-sei=Teraoka en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MoriseMasahiro en-aut-sei=Morise en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Niigata Cancer Center Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine and Allergy, Fujita Health University kn-affil= affil-num=4 en-affil=Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Tottori University kn-affil= affil-num=5 en-affil=Graduate School of Medical Sciences, Research Institute for Diseases of the Chest, Kyushu University kn-affil= affil-num=6 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Nagoya University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University kn-affil= en-keyword=Subgroup analysis kn-keyword=Subgroup analysis en-keyword=Guideline kn-keyword=Guideline en-keyword=Lung cancer kn-keyword=Lung cancer END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=6 article-no= start-page=e86575 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250623 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Retreatment With EGFR-Tyrosine Kinase Inhibitor After Disease Progression Following Gefitinib Induction and Chemoradiotherapy in EGFR-Mutant Stage III Non-small Lung Cancer: An Efficacy and Safety Analysis of the LOGIK0902/OLCSG0905 Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and objective: We had previously conducted a phase II study (LOGIK0902/OLCSG0905 study) involving the eight-week administration of gefitinib, followed by cisplatin-based chemoradiotherapy, to treat locally advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC). Despite favorable overall survival outcomes, more than half of the patients relapsed after the protocol therapy, highlighting the need to clarify the clinical significance of retreatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated the efficacy and safety of EGFR-TKI retreatment after disease progression.
Materials and methods: We included 14 patients who relapsed after the protocol treatment and received any type of EGFR-TKI as post-progression treatment in this sub-analysis. We evaluated the efficacy and safety of retreatment with EGFR-TKI in these patients.
Results: Among the 14 patients, 11 (78.6%) responded to the induction of gefitinib in the treatment protocol. After relapse, 9/14 patients (64.3%) received gefitinib, 3/14 (21.4%) received afatinib, and 2/14 (14.3%) received erlotinib monotherapy, respectively. The median duration of post-progression EGFR-TKI treatment was 17.9 (0.7-45.5) months. The overall response rate (ORR) and disease control rate were 64.3% [9/14 patients; 95% confidence interval (CI): 35.1%-87.2%] and 85.7% (12/14 patients; 95% CI: 57.2%-98.2%), respectively. The median progression-free survival (PFS) and median survival durations after the initiation of EGFR-TKI retreatment were 11.8 months (95% CI: 5.7-20.7 months) and 47.4 months (95% CI: 31.8 months to not estimable), respectively. Adverse events were comparable to those previously reported.
Conclusions: Patients with disease progression after protocol therapy demonstrated sensitivity to retreatment with an EGFR-TKI, with acceptable safety. en-copyright= kn-copyright= en-aut-name=SaekiSho en-aut-sei=Saeki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=SakataShinya en-aut-sei=Sakata en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 ORCID= en-aut-name=ToyozawaRyo en-aut-sei=Toyozawa en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaradaDaijiro en-aut-sei=Harada en-aut-mei=Daijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaKentaro en-aut-sei=Tanaka en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=ShioyamaYoshiyuki en-aut-sei=Shioyama en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GembaKenichi en-aut-sei=Gemba en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SasakiTomonari en-aut-sei=Sasaki en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=BesshoAkihiro en-aut-sei=Bessho en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KishimotoJunji en-aut-sei=Kishimoto en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KatsuiKuniaki en-aut-sei=Katsui en-aut-mei=Kuniaki 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=SugioKenji en-aut-sei=Sugio en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, Kumamoto University Hospital kn-affil= affil-num=2 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Kumamoto University Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Kitakyushu Municipal Medical Center kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center kn-affil= affil-num=8 en-affil=Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=11 en-affil=Radiation Oncology, Ion Beam Therapy Center, SAGA HIMAT Foundation kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Chugoku Central Hospital kn-affil= affil-num=13 en-affil=Department of Radiation Oncology, Iizuka Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=15 en-affil=Center for Clinical and Translational Research, Kyushu University Hospital kn-affil= affil-num=16 en-affil=Department of Radiology, Division of Radiation Oncology, Kawasaki Medical School kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Thoracic and Breast Surgery, Oita University kn-affil= en-keyword=chemoradiotherapy kn-keyword=chemoradiotherapy en-keyword=egfr kn-keyword=egfr en-keyword=locally advanced setting kn-keyword=locally advanced setting en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=progression kn-keyword=progression en-keyword=retreatment kn-keyword=retreatment en-keyword=safety kn-keyword=safety en-keyword=targeted therapy kn-keyword=targeted therapy END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=4 article-no= start-page=e82046 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gastrointestinal Stromal Tumors in the Stomach With Tumor Growth and Hemorrhage During Conservative Management: A Report of Two Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gastrointestinal stromal tumors (GISTs) are often detected incidentally during esophagogastroduodenoscopy. Although surgical resection is the standard treatment for GISTs, patients with significant comorbidities may not be eligible for surgery and are managed conservatively. Herein, we report two cases of gastric GISTs that were initially observed during the management of other comorbidities but subsequently became enlarged, resulting in gastrointestinal bleeding. These cases highlight the potential risks of tumor progression and bleeding in patients undergoing conservative management. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya 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=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, 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 Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=conservative management kn-keyword=conservative management en-keyword=gastric subepithelial lesion kn-keyword=gastric subepithelial lesion en-keyword=gastrointestinal bleeding kn-keyword=gastrointestinal bleeding en-keyword=gastrointestinal stromal tumor kn-keyword=gastrointestinal stromal tumor en-keyword=tumor growth kn-keyword=tumor growth END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=2 article-no= start-page=363 end-page=368 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Microsatellite-high intrahepatic cholangiocarcinoma with favorable treatment outcome using pembrolizumab en-subtitle= kn-subtitle= en-abstract= kn-abstract=Intrahepatic cholangiocarcinoma has a poor prognosis. In unresectable cases, the survival period is short despite combination therapy with cytotoxic anticancer agents and immune checkpoint inhibitors. The usefulness of immune checkpoint inhibitors against malignant tumors with microsatellite instability-high (MSI-H) mutations was shown in the KEYNOTE158 study; however, data for intrahepatic cholangiocarcinoma are insufficient. In the present case, a 65-year-old man with intrahepatic cholangiocarcinoma and lymph node metastasis could not be treated with a combination of gemcitabine, CDDP, and S-1. A comprehensive cancer genomic profiling (CGP) test showed MLH1 pathogenic mutation and MSI-H. When pembrolizumab was administered, the tumor shrinkage effect was rapidly observed, which was sustained even after 30 months. No pathogenic mutations were observed in the germline test, and MSI-high was considered to be due to the MLH1 pathogenic mutation occurring sporadically in somatic cells. MSI-H intrahepatic cholangiocarcinoma is extremely rare. However, because pembrolizumab is expected to be effective, CGP testing should be actively performed. en-copyright= kn-copyright= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatoHironari en-aut-sei=Kato en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorimotoKosaku en-aut-sei=Morimoto en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TerasawaHiroyuki en-aut-sei=Terasawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=Microsatellite instability (MSI)-high kn-keyword=Microsatellite instability (MSI)-high en-keyword=Tumor mutation burden (TMB)-high kn-keyword=Tumor mutation burden (TMB)-high en-keyword=Intrahepatic cholangiocarcinoma kn-keyword=Intrahepatic cholangiocarcinoma en-keyword=Comprehensive genome profiling kn-keyword=Comprehensive genome profiling END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=2 article-no= start-page=e79651 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gastric Metastasis of Renal Cell Carcinoma Initially Diagnosed by Esophagogastroduodenoscopy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Here, we report a rare case of renal cell carcinoma (RCC) initially detected as a gastric metastasis. A 58-year-old man with epigastric discomfort underwent esophagogastroduodenoscopy, which revealed a reddish semi-pedunculated lesion with a whitish coating. Biopsy and imaging confirmed clear cell RCC metastasis. Contrast-enhanced computed tomography (CT) revealed a primary renal tumor with pancreatic and lymph node metastases. Despite chemotherapy treatment, the patient died after 10 months. Gastric metastases from RCC, although rare, should be considered in highly vascular gastric lesions with white coatings. Clinicians must be vigilant for metastatic diseases with atypical gastric findings. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KamioTomohiro en-aut-sei=Kamio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirataShoichiro en-aut-sei=Hirata en-aut-mei=Shoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=clear renal cell carcinoma kn-keyword=clear renal cell carcinoma en-keyword=esophagogastroduodenoscopy (egd) kn-keyword=esophagogastroduodenoscopy (egd) en-keyword=gastric metastasis kn-keyword=gastric metastasis en-keyword=metastatic tumor, renal cell carcinoma (rcc) kn-keyword=metastatic tumor, renal cell carcinoma (rcc) 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=14 cd-vols= no-issue=2 article-no= start-page=e72067 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=Oculogyric Crisis During Chronic Aripiprazole Therapy: A Diagnostic Challenge in the Emergency Department en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oculogyric crisis can occur even during chronic, stable aripiprazole therapy without recent dose escalation. In patients with acute upward eye deviation and an otherwise normal neurologic examination, medication review is key to recognizing drug-induced dystonia and avoiding unnecessary neurologic workup. en-copyright= kn-copyright= en-aut-name=TokiokaKohei en-aut-sei=Tokioka en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuoIppei en-aut-sei=Matsuo en-aut-mei=Ippei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama Universitye, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Okayama University Japan kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=acute dystonia kn-keyword=acute dystonia en-keyword=aripiprazole kn-keyword=aripiprazole en-keyword=drug-induced movement disorder kn-keyword=drug-induced movement disorder en-keyword=oculogyric crisis kn-keyword=oculogyric crisis END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=11 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=Association of Wet-Bulb Globe Temperature with heat-related illness hospitalizations in Japan: a time-stratified, case-crossover study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Heat-related illnesses are a serious public health concern and are exacerbated by global warming. Wet-Bulb Globe Temperature (WBGT) is widely used as a heat stress indicator, but its clinical impact remains unclear. This study aimed to investigate the association between hourly variations in WBGT and the incidence of hospitalizations for heat-related illness in Japan using a nationwide database. By incorporating individual-level clinical data and performing stratified analyses, we sought to provide a more granular understanding of how heat exposure affects the risk of heat-related illness requiring hospitalization.
Methods We conducted a time-stratified, case-crossover study using data collected from July to September in 2020 and 2021 in the Heatstroke STUDY registry. The inclusion criteria were patients registered in the Heatstroke STUDY registry, specifically hospitalized patients with heat-related illness who were transported to participating hospitals during the study period. Hourly WBGT values were assigned based on the nearest monitoring station to each hospital. Conditional logistic regression and distributed lag models were used to estimate associations between WBGT and the risk of hospitalization.
Results A total of 1,653 heat-related illness hospitalizations were analyzed. The mean patient age was 67.9 years; 67.6% were male. Each 1 C increase in WBGT at onset (hospital arrival) was associated with a significantly increased risk of hospitalization (OR 1.10, 95% CI: 1.05?1.15). The cumulative effect over the prior six hours was also significant (OR 1.56, 95% CI: 1.50?1.62). Compared with WBGT? Conclusions Higher WBGT levels were associated with an increased risk of heat-related hospitalization. Although the effect appeared greater in some subgroups, only patients with mental disorders demonstrated statistically significant effect modification, suggesting elevated WBGT confers risk broadly. en-copyright= kn-copyright= en-aut-name=YamamuraYuka en-aut-sei=Yamamura en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HongoTakashi en-aut-sei=Hongo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasaiFumiya en-aut-sei=Sasai en-aut-mei=Fumiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TokiokaKohei en-aut-sei=Tokioka en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KandaJun en-aut-sei=Kanda en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YokoboriShoji en-aut-sei=Yokobori en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Emergency and Critical Care Medicine, Nippon Medical School Musashikosugi Hospital kn-affil= affil-num=9 en-affil=Department of Emergency and Critical Care Medicine, Nippon Medical School kn-affil= affil-num=10 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Wet-Bulb Globe Temperature kn-keyword=Wet-Bulb Globe Temperature en-keyword=Heat stroke kn-keyword=Heat stroke en-keyword=Heat related illness kn-keyword=Heat related illness en-keyword=Global warming kn-keyword=Global warming END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=5 article-no= start-page=372 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=Alpha-Ketoglutarate Drives an Osteogenic and Extracellular Matrix Gene Program in Periodontal Ligament Fibroblasts via Selective Reduction of H3K27me3 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontal disease damages the tissues that support teeth and can ultimately lead to tooth loss, yet effective treatments to regenerate these tissues are still limited. Recent studies have shown that substances produced during normal cellular metabolism can influence how genes are regulated, but their role in periodontal regeneration has not been fully clarified. In this study, we investigated whether alpha-ketoglutarate, a naturally occurring metabolite involved in energy production, could promote periodontal tissue regeneration. We found that alpha-ketoglutarate enhanced bone-related and extracellular matrix-related gene expression in human periodontal ligament cells by reducing a repressive gene-regulatory signal that normally suppresses these genes. Importantly, alpha-ketoglutarate did not broadly alter chromatin accessibility, indicating that its effects were mediated through selective gene regulation. Furthermore, oral administration of alpha-ketoglutarate promoted alveolar bone regeneration and collagen-rich tissue formation in a mouse model of periodontal disease. Because alpha-ketoglutarate is a naturally occurring molecule in the body, these findings suggest that metabolite-based regulation of gene activity may represent a promising and safe approach for periodontal tissue regeneration. en-copyright= kn-copyright= en-aut-name=HasegawaRyu en-aut-sei=Hasegawa en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiShigeki en-aut-sei=Suzuki en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FahrezaRahmad Rifqi en-aut-sei=Fahreza en-aut-mei=Rahmad Rifqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsaiShin-Ho en-aut-sei=Tsai en-aut-mei=Shin-Ho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DaidoujiYoshino en-aut-sei=Daidouji en-aut-mei=Yoshino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriMasato en-aut-sei=Omori en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KajikawaTetsuhiro en-aut-sei=Kajikawa en-aut-mei=Tetsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamadaSatoru en-aut-sei=Yamada en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=2 en-affil=Department of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=4 en-affil=Department of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=6 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=7 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=8 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= en-keyword=alpha-ketoglutarate kn-keyword=alpha-ketoglutarate en-keyword=periodontal ligament kn-keyword=periodontal ligament en-keyword=extracellular matrix kn-keyword=extracellular matrix en-keyword=epigenetic regulation kn-keyword=epigenetic regulation en-keyword=H3K27me3 kn-keyword=H3K27me3 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=20260221 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Turning pancreatic cancer from cold to hot: the promise of a p53-expressing oncolytic adenovirus (OBP-702) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pancreatic cancer remains one of the most lethal malignancies, with limited therapeutic options and poor responsiveness to immune checkpoint inhibitors (ICIs). This resistance is largely attributed to its profoundly immunosuppressive and desmoplastic tumor microenvironment (TME), characterized by low tumor mutational burden, dense stroma, and abundant immunosuppressive cell populations. Therefore, strategies capable of enhancing tumor immunogenicity and overcoming immune evasion are urgently needed. Oncolytic virotherapy is a promising approach, offering not only tumor-selective cytotoxicity, but also potent immunomodulatory effects. Of these agents, Telomelysin (OBP-301, Suratadenoturev), a telomerase-specific oncolytic adenovirus, demonstrated clinical safety but limited efficacy in refractory tumors. To address this challenge, we developed OBP-702, a next-generation, p53-armed, oncolytic adenovirus designed to augment antitumor activity. Preclinical studies have shown that OBP-702 exerts robust cytotoxicity through multiple mechanisms, including p53-mediated apoptosis and autophagy, E1A?E2F1-mediated p21 suppression, and inhibition of oncogenic KRAS pathways. Importantly, OBP-702 induces strong immunogenic cell death, activates dendritic cells, and promotes tumor-specific T-cell responses, effectively converting immunologically gcoldh pancreatic tumors into ghoth tumors. OBP-702 also remodels the immunosuppressive TME by reducing granulocyte?macrophage colony-stimulating factor (GM-CSF) secretion, suppressing myeloid-derived suppressor cells (MDSCs), and targeting stromal components, such as cancer-associated fibroblasts (CAFs). These effects contribute to enhanced responses to ICIs and standard chemotherapies. Given its multifaceted antitumor functions and ability to overcome key barriers in pancreatic cancer, OBP-702 represents a highly promising therapeutic candidate. A first-in-human clinical trial evaluating endoscopic ultrasonography-guided intratumoral injection of OBP-702 is currently in preparation, expected to advance clinical translation of this novel virotherapeutic strategy. en-copyright= kn-copyright= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji 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=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=Center for Innovative Clinical Medicine, Okayama University Hospital 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=Oncolys BioPharma Inc kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Oncolytic adenovirus kn-keyword=Oncolytic adenovirus en-keyword=p53 kn-keyword=p53 en-keyword=OBP-702 kn-keyword=OBP-702 en-keyword=Immunogenic cell death kn-keyword=Immunogenic cell death en-keyword=Tumor microenvironment kn-keyword=Tumor microenvironment en-keyword=Pancreatic cancer kn-keyword=Pancreatic cancer 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 Japanfs 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 systemfs 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=6 cd-vols= no-issue=1 article-no= start-page=96 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260109 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of an oral exercise intervention on pre-frailty or frailty in older people: a randomized clinical trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Frailty is often experienced by older adults, which can lead to long-term health problems. We aimed to examine associations with improvements in nutritional status, sarcopenia (age-related loss of skeletal muscle mass and strength), and frailty in four groups with different oral exercise frequencies.
Methods: We conducted a prospective, parallel multi-arm randomized controlled trial (Japan Registry of Clinical Trials (jRCT) 1062210063) to test the effects of oral exercise on frailty in older adults. Each intervention consisted of a standardized oral exercise protocol including neck exercises, lip exercises, and tongue movements, designed to improve oral function and reduce frailty. The primary outcome was the change in the number of frailty criteria from baseline to follow-up. Individuals aged ?60 years were screened for frailty status using standardized criteria at the Department of Preventive Dentistry at Okayama University Hospital between October 2022 and December 2023. Those identified as pre-frailty or frailty were eligible and enrolled in the study. After screening 60 individuals, 58 eligible participants were randomly assigned using block randomization to one of four oral exercise frequency groups: 3 times/day & everyday, 3 times/day & 3 days/week, once/day & everyday, and once/day & 3 days/week. A two-way repeated measures analysis of variance was used to evaluate the impact of the four frequencies of oral exercise methods on frailty in older adults. Outcome assessors were blinded; participants were not.
Results: Here we show the results of the 58 participants. Group sizes are: 3 times/day & everyday (n?=?14), 3 times/day & 3 days/week (n?=?15), once/day & everyday (n?=?14), once/day & 3 days/week (n?=?15). The trial is completed as planned, and all randomized participants are analyzed. The main effect of time is significant for the number of frailty criteria (F?=?14.803, p? Conclusions: After conducting oral exercises for 3 months on older adults with pre-frailty or frailty, improvements in frailty are observed. Overall, these exercises could be a simple, low-cost way to support healthy aging in the community. 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=SawadaNanami en-aut-sei=Sawada en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InadaSakura en-aut-sei=Inada en-aut-mei=Sakura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=Section of Preventive and Public Health Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University kn-affil= affil-num=3 en-affil=Division of Health Promotion, Okayama-City Health Center kn-affil= affil-num=4 en-affil=Department of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health Care kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue= article-no= start-page=e5 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=Effects of sagging correction calibration error on radiation therapy equipment using image analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: This study investigates the effect of sagging correction errors on image quality and geometric coordinate accuracy.
Methods: This study utilised the Elekta radiotherapy system, ball bearing (BB), Catphan phantom and MultiMet-WL phantom. Ten distinct flex maps (FMs) were acquired by positioning the BB at the accuracy isocentre and introducing shifts of 0.2, 0.4 and 0.6 mm in the left, table and up directions, respectively. Cone-beam computed tomography images of the Catphan phantom were acquired using 10 FMs. The images were analysed for modulation transfer function (MTF) values and geometric coordinates. Additionally, the Winston?Lutz (W-L) test was conducted under reference couch positions and with a 0.3 mm couch shift.
Results: For the Catphan phantom analysis, the standard deviations of MTF10% across FMs were 0.19. The centre-of-gravity coordinates of the insert exhibited shifts of approximately 0.2, 0.4 and 0.6 mm when comparing reference images to those acquired with the shifted FMs. The results of the W-L test with a 0.3 mm couch shift showed radiation isocentre deviations exceeding 1 mm compared to the reference couch positions.
Conclusions: Minor sagging correction calibration errors did not remarkably impact image quality; however, they altered the geometric coordinates of the image isocentre. These calibration errors decreased the accuracy of off-isocentre positioning. en-copyright= kn-copyright= en-aut-name=FujiiYasushi en-aut-sei=Fujii en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakayamaTakahiro en-aut-sei=Nakayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OshitaJunki en-aut-sei=Oshita en-aut-mei=Junki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsunodaAyaka en-aut-sei=Tsunoda en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaekiYusuke en-aut-sei=Saeki en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanabeYoshinori en-aut-sei=Tanabe en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Radiology, Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers kn-affil= affil-num=2 en-affil=Department of Radiology, Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers kn-affil= affil-num=3 en-affil=Department of Radiology, Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers kn-affil= affil-num=4 en-affil=Department of Radiology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Kawasaki Medical School Hospital kn-affil= affil-num=6 en-affil= Faculty of Medicine, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=flex map kn-keyword=flex map en-keyword=sagging kn-keyword=sagging en-keyword=Winston?Lutz test kn-keyword=Winston?Lutz test END start-ver=1.4 cd-journal=joma no-vol=164 cd-vols= no-issue= article-no= start-page=108315 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=Global trends in Clostridioides difficile infection?related mortality, 2001-2023: An observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Clostridioides difficile infection (CDI) is a major public health concern, particularly in aging populations. The aim of this study was to evaluate global trends in CDI-related mortality to inform sustainable and cost-effective management strategies.
Methods: We conducted an observational study using mortality data from the World Health Organization (WHO) database spanning 2001 to 2023. Sixty-three countries with satisfactory data quality and at least 12 years of data between 2001 and 2023 were included. Crude and age-standardized CDI-related mortality rates per 1,000,000 individuals were calculated after stratification by age, sex, WHO region, and sociodemographic index (SDI). Global trends were analyzed using locally weighted regression.
Results: The global age-standardized CDI-related mortality rate was 0.76 per 1,000,000 individuals in 2001, peaked at 4.08 in 2010, and declined to 2.44 in 2023. The most notable downward trends were observed in the Americas and high-SDI countries. These improvements may reflect the impact of multidisciplinary efforts in CDI prevention and management.
Conclusions: Although CDI-related mortality has declined globally over the past decade, the disease remains a significant threat, especially in older populations. Ongoing global efforts are essential to further reduce CDI-related deaths. en-copyright= kn-copyright= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaKo en-aut-sei=Harada en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoMaki en-aut-sei=Yamamoto en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=VuQuynh Thi en-aut-sei=Vu en-aut-mei=Quynh Thi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BelangoyKeith Pardillada en-aut-sei=Belangoy en-aut-mei=Keith Pardillada kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OuddoudHanane en-aut-sei=Ouddoud en-aut-mei=Hanane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=2 en-affil=Division of Hematology/Oncology, Mayo Clinic kn-affil= affil-num=3 en-affil=Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=4 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Aging kn-keyword=Aging en-keyword=Locally weighted regression model kn-keyword=Locally weighted regression model en-keyword=Infection kn-keyword=Infection en-keyword=Clostridioides difficile kn-keyword=Clostridioides difficile en-keyword=Disparity kn-keyword=Disparity 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=112 cd-vols= no-issue=2 article-no= start-page=2301 end-page=2310 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Total thymectomy is oncologically superior to partial thymectomy in patients with thymic carcinoma: insights from a multicenter real-world data analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Although total thymectomy has been the standard surgical approach for thymic epithelial tumors, an increasing number of recent reports suggest that partial thymectomy for early-stage thymomas may yield outcomes comparable to those of total thymectomy. However, whether partial thymectomy is a viable alternative for thymic carcinoma remains unclear.
Materials and methods: A total of 106 patients with thymic carcinoma underwent curative intended resection at 19 institutions between January 2010 and December 2021. Excluding 14 patients with incomplete resection, 92 patients with thymic carcinoma who underwent total (n = 73) or partial thymectomy (n = 19) were compared. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan?Meier curves and Cox proportional hazard models. Overlap weighting was applied to adjust for potential confounding factors.
Results: Among patients with clinical stage I disease, 79.3% were upstaged to stage II or higher postoperatively. Unadjusted analyses revealed no statistically significant differences in OS and RFS between the total and partial thymectomy groups, although a trend toward poorer outcomes in the partial thymectomy group was observed. After overlap weighting, partial thymectomy was associated with significantly poorer OS (P = 0.0027) and higher recurrence risk (P < 0.0001). Early postoperative recurrence occurred more frequently in the partial thymectomy group.
Conclusion: Partial thymectomy was associated with significantly worse survival and recurrence outcomes in thymic carcinoma. Given the limitations of preoperative diagnosis, total thymectomy should remain the preferred surgical approach for undiagnosed thymic epithelial tumors to achieve optimal oncologic control and minimize the risk of recurrence. en-copyright= kn-copyright= en-aut-name=HayashiTatsuya en-aut-sei=Hayashi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HabuTomohiro en-aut-sei=Habu en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko 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=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OtsukaTomoaki en-aut-sei=Otsuka en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeMototsugu en-aut-sei=Watanabe en-aut-mei=Mototsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KurosakiTakeshi en-aut-sei=Kurosaki en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamadaEiji en-aut-sei=Yamada en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsudaEisuke en-aut-sei=Matsuda en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HayashiTatsurou en-aut-sei=Hayashi en-aut-mei=Tatsurou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= en-aut-name=HayamaMakio en-aut-sei=Hayama en-aut-mei=Makio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TaoHiroyuki en-aut-sei=Tao en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 ORCID= en-aut-name=HiramiYuji en-aut-sei=Hirami en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=WashioKazuhiro en-aut-sei=Washio en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MisaoTakahiko en-aut-sei=Misao en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 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=23 ORCID= en-aut-name=SanoYoshifumi en-aut-sei=Sano en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 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=25 ORCID= en-aut-name=KawamataOsamu en-aut-sei=Kawamata en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 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=27 ORCID= affil-num=1 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=2 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=3 en-affil=Center of Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=6 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=7 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=8 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=9 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=10 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=11 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=12 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=13 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=14 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=15 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=16 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=17 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=18 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=19 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=20 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=21 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=22 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=23 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=24 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=25 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=26 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=27 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=partial thymectomy kn-keyword=partial thymectomy en-keyword=real-world data analysis kn-keyword=real-world data analysis en-keyword=retrospective comparative cohort study kn-keyword=retrospective comparative cohort study en-keyword=thymic carcinoma kn-keyword=thymic carcinoma en-keyword=thymic epithelial tumors kn-keyword=thymic epithelial tumors en-keyword=total thymectomy kn-keyword=total thymectomy 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=20260219 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Induction of IL-9-producing CD8+ T cells by ascochlorin derivatives en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Purpose: Ascochlorin (ASC) is an antiviral antibiotic from the fermented broth of Ascochyta viciae which exerts an inhibitory effect to cancers. Its impact on immune cells has not been examined. In this study, we obtained ASC derivatives with less cytotoxicity and determined whether they affected T cells, indicating possible immune-mediated antitumour effects.
Experimental Approach: Newly synthesised ASC derivatives were screened for inhibitory effects on T-cell antigen receptor (TCR)-stimulated proliferative responses using murine CD4+ and CD8+ T cells. Two compounds were identified that exhibited >10-fold less toxicity compared with ASC. N184, the less toxic of the two, was analysed for its in vivo antitumour effects, and in vitro effects on CD8+ T-cell proliferation, survival, cytokine production and exhaustion, using microscopy, qPCR and flow cytometry.
Key Results: N184 induced limited IL-9 production in CD8+ T cells following TCR stimulation, thereby improving cell survival. It also enhanced cytokine production in the late phase of proliferation and suppressed the induction of exhaustion. N184 suppressed tumour growth in mice in a CD8+ T cell-dependent manner. The effect was partially prevented by an IL-9-neutralising antibody.
Conclusion and Implications: N184 induces differentiation of IL-9-producing CD8+ T cells in vitro and elicits antitumour immunity in an IL-9-dependent manner. en-copyright= kn-copyright= en-aut-name=ImanoNatsumi en-aut-sei=Imano en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishidaMikako en-aut-sei=Nishida en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokumasuMiho en-aut-sei=Tokumasu en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhaoWeiyang en-aut-sei=Zhao en-aut-mei=Weiyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamashitaNahoko en-aut-sei=Yamashita en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Immunology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Immunology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Immunology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=ascochlorin derivative kn-keyword=ascochlorin derivative en-keyword=CD8 positive T lymphocytes kn-keyword=CD8 positive T lymphocytes en-keyword=cell survival kn-keyword=cell survival en-keyword=IFN- kn-keyword=IFN- en-keyword=interleukin-9 kn-keyword=interleukin-9 en-keyword=Tc9 kn-keyword=Tc9 en-keyword=tumour immunity kn-keyword=tumour immunity END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue= article-no= start-page=1673581 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260107 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Binding of IgA1 and surface-expressed collagen-binding protein of Streptococcus mutans contributes to IgA nephropathy pathogenesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The present study was conducted to examine the interaction between collagen-binding protein (Cnm) of Streptococcus mutans and immunoglobulin (IgA) to clarify the possible involvement in IgA nephropathy (IgAN) development.
Methods: The binding of Cnm to human immunoglobulins was examined using an enzyme-linked immunosorbent assay. A nephritis-induced rat model was employed to confirm the localization of Cnm.
Results: IgA1 showed significantly greater binding ability to Cnm than to other bacterial surface proteins, and Cnm showed significantly greater binding ability to IgA1 than to other immunoglobulins. In rats administered Cnm, IgA deposition was observed in the glomerular mesangial region. Furthermore, biotin-labeled Cnm was observed in the same region as IgA deposition in the Cnm group.
Conclusions: Taken together, it is considered that following invasion into the bloodstream, Cnm binds to and forms a complex with IgA1, leading to deposition of IgA1 in renal glomeruli. en-copyright= kn-copyright= en-aut-name=MatsuokaDaiki en-aut-sei=Matsuoka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SueharaKana en-aut-sei=Suehara en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakaShuhei en-aut-sei=Naka en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MisakiTaro en-aut-sei=Misaki en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagasawaYasuyuki en-aut-sei=Nagasawa en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoSeigo en-aut-sei=Ito en-aut-mei=Seigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuehiroYuto en-aut-sei=Suehiro en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NomuraRyota en-aut-sei=Nomura en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanoKazuhiko en-aut-sei=Nakano en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Matsumoto-NakanoMichiyo en-aut-sei=Matsumoto-Nakano en-aut-mei=Michiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Nephrology, Seirei Hamamatsu General Hospital kn-affil= affil-num=5 en-affil=Department of General Internal Medicine, Hyogo Medical University kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Japan Self-Defense Force Iruma Hospital kn-affil= affil-num=7 en-affil=Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka kn-affil= affil-num=8 en-affil=Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=9 en-affil=Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka kn-affil= affil-num=10 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=bacterial surface proteins kn-keyword=bacterial surface proteins en-keyword=collagen-binding protein kn-keyword=collagen-binding protein en-keyword=human immunoglobulins kn-keyword=human immunoglobulins en-keyword=IgA nephropathy kn-keyword=IgA nephropathy en-keyword=Streptococcus mutans kn-keyword=Streptococcus mutans END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=2 article-no= start-page=110 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 Slide Annotation System with Multimodal Analysis for Video Presentation Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=With the rapid growth of online presentations, there has been an increasing need for efficient review of recorded materials. In typical presentations, speakers verbally elaborate on each slide, providing details not captured in the slides themselves. Automatically extracting and embedding these verbal explanations at their corresponding slide locations can greatly enhance the review process for audiences. This paper presents a Slide Annotation System that employs a robust hybrid two-stage detector to identify slide boundaries, extracts slide text through Optical Character Recognition (OCR), transcribes narration, and employs a multimodal Large Language Model (LLM) to generate concise, context-aware annotations that are added to their corresponding slide locations. For evaluations, the technical performance was validated on five recorded presentations, while the user experience was assessed by 37 participants. The results showed that the system achieved a macro-average ?1 score of 0.879 (??=0.024, 95% ??[0.849,0.909]) for slide segmentation and 90.0% accuracy (95% ??[74.4%,96.5%]) for annotation alignment. Subjective evaluations revealed high annotation validity and usefulness as rated by presenters, and a high System Usability Scale (SUS) score of 80.5 (??=6.7, 95% ??[78.3,82.7]). Qualitative feedback further confirmed that the system effectively streamlined the review process, enabling users to locate key information more efficiently than standard video playback. These findings demonstrate the strong potential of the proposed system as an effective automated annotation system. en-copyright= kn-copyright= en-aut-name=HazAmma Liesvarastranta en-aut-sei=Haz en-aut-mei=Amma Liesvarastranta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BrataKomang Candra en-aut-sei=Brata en-aut-mei=Komang Candra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FunabikiNobuo en-aut-sei=Funabiki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KyawHtoo Htoo Sandi en-aut-sei=Kyaw en-aut-mei=Htoo Htoo Sandi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FajriantiEvianita Dewi en-aut-sei=Fajrianti en-aut-mei=Evianita Dewi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SukaridhotoSritrusta en-aut-sei=Sukaridhoto en-aut-mei=Sritrusta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=5 en-affil=Human Centric Multimedia Research Laboratory, Department of Informatic and Computer Engineering, Politeknik Elektronika Negeri Surabaya kn-affil= affil-num=6 en-affil=Human Centric Multimedia Research Laboratory, Department of Informatic and Computer Engineering, Politeknik Elektronika Negeri Surabaya kn-affil= en-keyword=slide annotation kn-keyword=slide annotation en-keyword=multimodal analysis kn-keyword=multimodal analysis en-keyword=speech-to-text kn-keyword=speech-to-text en-keyword=LLM kn-keyword=LLM en-keyword=SUS kn-keyword=SUS END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1 article-no= start-page=69 end-page=74 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=Effective Treatment of Advanced Hepatocellular Carcinoma with Extensive Peritoneal Dissemination Using Lenvatinib en-subtitle= kn-subtitle= en-abstract= kn-abstract=Patients with hepatocellular carcinoma (HCC) and extensive peritoneal dissemination generally have a poor prognosis and are often resistant to systemic therapy. We report the case of a 47-year-old woman with HCC and massive peritoneal dissemination who presented with malignant ascites requiring repeated cell-free and concentrated ascites reinfusion therapy and peritoneovenous shunt placement, as well as malignant pleural effusion requiring pleurodesis. Combined immunotherapy with durvalumab/tremelimumab was initiated;however, disease progression was observed after three treatment courses, prompting a switch to lenvatinib therapy. Two months after initiation of lenvatinib, CT imaging demonstrated complete disappearance of arterial enhancement in the primary hepatic lesion, along with reduction in the size of peritoneal dissemination nodules. Thirteen months after switching to lenvatinib (16 months after the initial diagnosis), the alpha-fetoprotein level continued to decrease, and the disease remained stable under treatment. Despite the extremely high tumor burden, lenvatinib achieved disease stabilization and symptomatic improvement. en-copyright= kn-copyright= en-aut-name=WakatsukiShinya en-aut-sei=Wakatsuki en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=UenoAkiko en-aut-sei=Ueno en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NambaTakaomi en-aut-sei=Namba en-aut-mei=Takaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoYorito en-aut-sei=Yamamoto en-aut-mei=Yorito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, 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 Obstetrics and Gynecology, Kochi Health Sciences Center kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Kochi Health Sciences Center kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, 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 Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= en-keyword=diagnostic laparoscopy kn-keyword=diagnostic laparoscopy en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma en-keyword=peritoneal dissemination kn-keyword=peritoneal dissemination en-keyword=lenvatinib kn-keyword=lenvatinib END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1 article-no= start-page=63 end-page=67 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=Metastatic Intraocular Tumor Likely from Hepatocellular Carcinoma Mimicking Panuveitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 77-year-old man undergoing treatment for hepatocellular carcinoma (HCC) presented with blurred vision in his right eye, persisting for 2 months. Slit-lamp microscopy and fundus examination revealed inflammatory cells in the anterior chamber, severe vitreous opacities, and retinal vasculitis in the right eye. The patient underwent vitreous surgery with biopsy, and vitreous cytology confirmed a metastatic intraocular tumor originating from the HCC. Radiotherapy was administered to the right eye, with no recurrence of intraocular inflammation observed at 10 months post-irradiation. en-copyright= kn-copyright= en-aut-name=TakasuEri en-aut-sei=Takasu en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KindoHiroya en-aut-sei=Kindo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KimuraShuhei en-aut-sei=Kimura en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HosokawaMio en-aut-sei=Hosokawa en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KanzakiYuki en-aut-sei=Kanzaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AdachiTakuya en-aut-sei=Adachi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=metastatic intraocular tumor kn-keyword=metastatic intraocular tumor en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma en-keyword=panuveitis kn-keyword=panuveitis en-keyword=uveitis masquerade syndrome kn-keyword=uveitis masquerade syndrome 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 agentsf prescribing patterns and the patient outcomes following the policy shift. We conducted a multicenter retrospective study at four hospitals in Japanfs 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 patientsf clinical data from the electronic database. The studyfs 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=47 end-page=54 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=Time Course of the Development and Loss of Delta-9-tetrahydrocannabinol Tolerance: Effects on Hypothermia and Spontaneous Locomotor Activity in Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Deregulation of cannabis use is gradually expanding in Europe and the United States. However, the biological processes driving tolerance to delta-9-tetrahydrocannabinol (9-THC), the main psychoactive component of cannabis, remain unclear. Thus, this study aimed to investigate the mechanisms and time course of tolerance development and loss to 9-THC in mice. Male ICR mice (7 weeks old) were administered 9-THC once daily for 3 days and then divided into three groups according to the washout period (3-, 10-, and 17-day washout groups). After each washout, changes in body temperature and locomotor activity were measured following re-exposure to 9-THC. Furthermore, the mRNA expression levels of CB1 and CB2 receptors in the brain were evaluated using real-time PCR. On day 1, significant hypothermia and reduced spontaneous locomotor activity were observed in the 9-THC-treated mice compared with the vehicle-treated mice. Tolerance to the hypothermic and locomotor-suppressing effects of 9-THC developed on days 2 and 3, respectively, and dissipated after 3 and 11 days of washout, respectively. These differences in the rates of tolerance development and recovery may reflect distinct underlying mechanisms. No significant changes in receptor mRNA expression were observed. These findings highlight the complexity of 9-THC tolerance and its potential implications for long-term cannabis use. en-copyright= kn-copyright= en-aut-name=EguchiYukiomi en-aut-sei=Eguchi en-aut-mei=Yukiomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UshioSoichiro en-aut-sei=Ushio en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IrieKeiichi en-aut-sei=Irie en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamashitaYuta en-aut-sei=Yamashita en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EguchiMiyu en-aut-sei=Eguchi en-aut-mei=Miyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoTakafumi en-aut-sei=Nakano en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MishimaKenichi en-aut-sei=Mishima en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=2 en-affil=Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=3 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=4 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=5 en-affil=Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=6 en-affil=Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=7 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= en-keyword=delta-9-tetrahydrocannabinol kn-keyword=delta-9-tetrahydrocannabinol en-keyword=cannabis kn-keyword=cannabis en-keyword=tolerance kn-keyword=tolerance en-keyword=locomotor kn-keyword=locomotor en-keyword=hypothermic kn-keyword=hypothermic END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1 article-no= start-page=39 end-page=46 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=Kinesiophobia Is Associated with Disability, Poor Quality of Life, Psychological Morbidity, and Surgery Dissatisfaction in Patients with Lumbar Microdiscetomy: A Cross-Sectional Controlled Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The study aimed to determine the prevalence of kinesiophobia in patients who had undergone lumbar microdiscectomy and to examine its associations with pain intensity, disability, quality of life, depression, anxiety, and satisfaction with surgery. Forty-eight patients with microdiscectomy and 48 healthy controls were enrolled. The Tampa Scale for Kinesiophobia (TSK), Roland-Morris Disability Index (RMDI), Hospital Anxiety and Depression Scale (HADS-A and HADS-D, respectively), and Short Form-36 Health Survey (SF-36) were administered to both groups. The scores of TSK, RMDI, HADS-A, and HADS-D were significantly higher and SF-36 scores were significantly lower in the microdiscectomy than the control group (p<0.001 for all). In the microdiscectomy group, median (min-max) RMDI, HADS-A, and HADS-D scores were 19 (4-34), 10 (0-18), and 9 (0-18), respectively, in kinesiophobic patients, and were significantly higher than 6 (2-20), 3 (0-11), 2.5 (0-11) in non-kinesiophobic patients (all p<0.001). The median (min-max) SF-36 PCS, SF-36 MCS, and VAS scores for surgery satisfaction were 36.5 (8.7-75), 52.1 (11-95), 5, 5 (0-10), respectively, in kinesiophobic patients and were significantly lower than 71 (28-95), 85.5 (9-93), 8.5 (3-10) in non-kinesiophobic patients (all p<0.05). TSK scores were significantly correlated with RMDI, HADS-A, HADS-D, SF-36, and surgery satisfaction scores (all p<0.05). Kinesiophobic patients with lumbar microdiscectomy therefore showed greater disability and psychological morbidity, poorer quality of life, and lower satisfaction with surgery. en-copyright= kn-copyright= en-aut-name=TezelNihal en-aut-sei=Tezel en-aut-mei=Nihal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=CanAsl? Gen?ay en-aut-sei=Can en-aut-mei=Asl? Gen?ay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Physical and Rehabilitation Medicine, Health Sciences University kn-affil= affil-num=2 en-affil=Department of Physical and Rehabilitation Medicine, Faculty of Medicine, Ankara Y?ld?r?m Beyaz?t University kn-affil= en-keyword=kinesiophobia kn-keyword=kinesiophobia en-keyword=microdiscectomy kn-keyword=microdiscectomy en-keyword=disability kn-keyword=disability en-keyword=quality of life kn-keyword=quality of life en-keyword=depression kn-keyword=depression END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1 article-no= start-page=31 end-page=37 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=The Preoperative Anterior Pelvic Plane Angle Predicts Cup Anteversion Changes at 1 Year after Total Hip Arthroplasty en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated global alignment changes following total hip arthroplasty (THA) and predictive alignment parameters for increased cup anteversion (CA) by retrospectively analyzing the primary THA data of 75 patients treated at our hospital (49 women, 26 men; age 65.1}5.7 years, BMI 28.3}3.4 kg/m2). Global alignment parameters, i.e., the anterior pelvic plane angle (APPa) and proximal femoral shaft angle (PFSa) and other alignment parameters were measured. CA was evaluated based on the patientsf standing coronal radiographs. CA was defined as the difference in CA from 2 weeks before to 1 year after each THA. We classified the cases as stable (S) (CA < 10; n=63) and pelvic retroversion (R) (CA ? 10; n=12) groups. Associations between CA and alignment parameters were evaluated by linear regression and a receiver operating characteristic (ROC) analysis. A significant decrease in the PFSa occurred between the 2-week and 1-year post-THA timepoints (7.8}4.3 vs. 4.2}3.6, p<0.001), with no notable change in other alignment parameters. At 1-year post-THA, the CA of 12 (16%) patients had increased to 4.5}4.4. Only the preoperative APPa was positively associated with CA (=0.165, p=0.020). The ROC analysis revealed that the optimal cut-off value for increased CA in the APPa is 2.1 (area under the curve, 0.700; p=0.020; odds ratio, 4.80). The APPa change predicted increased CA, which emphasizes the importance of the use of preoperative standing radiography for identifying the optimal cup positioning for post-THA changes in CA. en-copyright= kn-copyright= en-aut-name=IshibashiKyota en-aut-sei=Ishibashi en-aut-mei=Kyota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OishiHirotaka en-aut-sei=Oishi en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ArakiRyo en-aut-sei=Araki en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawamuraKosuke en-aut-sei=Kawamura en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SasakiIsamu en-aut-sei=Sasaki en-aut-mei=Isamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SasakiEiji en-aut-sei=Sasaki en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamadaHikaru en-aut-sei=Kamada en-aut-mei=Hikaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KogawaMasakazu en-aut-sei=Kogawa en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaSunao en-aut-sei=Tanaka en-aut-mei=Sunao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NumasawaTakuya en-aut-sei=Numasawa en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshibashiYasuyuki en-aut-sei=Ishibashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine kn-affil= en-keyword=total hip arthroplasty kn-keyword=total hip arthroplasty en-keyword=global alignment kn-keyword=global alignment en-keyword=anterior pelvic plane kn-keyword=anterior pelvic plane en-keyword=cup anteversion kn-keyword=cup anteversion en-keyword=pelvic tilt kn-keyword=pelvic tilt 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 scalefs 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=80 cd-vols= no-issue=1 article-no= start-page=9 end-page=16 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=A Novel Nomogram that Predicts Chronic Hemodialysis Patientsf Survival Based on Their Sedentary Behavior en-subtitle= kn-subtitle= en-abstract= kn-abstract=Appropriate treatments for chronic hemodialysis patients are a public health challenge in Japan. Sedentary behavior appears to be closely associated with these patientsf survival. We thus sought to develop a nomogram that predicts survival based on the duration of chronic hemodialysis patientsf sedentary behavior. One hundred twenty-four patients under chronic hemodialysis (73 men, 51 women, age 71.7}11.1 years) were enrolled in this cohort study. The patients wore a triaxial accelerometer that measured both their sedentary behavior, i.e., total sedentary behavior (minutes) and their maximum sedentary bouts (min) on non-hemodialysis days. We obtained the Kaplan-Meier curve and used the log-rank test and a Cox proportional hazards model to evaluate the relationship between the patientsf sedentary behavior and their survival. We also used a Cox proportional hazards model to develop a nomogram for the patientsf 5-year survival rate. Forty-six patients died during the follow-up period. When we stratified the patients by the medians of total sedentary behavior and maximum sedentary bouts, we observed significant between-group differences. After adjustment for confounding factors in a Cox proportional hazards model, total sedentary behavior and maximum sedentary bouts were identified as critical survival factors, and we generated a nomogram using an index of sedentary behavior. Our analysis results demonstrated that sedentary behavior on non-dialysis days was closely associated with the survival of the chronic hemodialysis patients, suggesting that a decrease in sedentary behavior would prolong their survival. The nomogram developed herein based on sedentary behavior may be useful for predicting the outcomes of chronic hemodialysis patients. en-copyright= kn-copyright= en-aut-name=SugaharaKentaro en-aut-sei=Sugahara en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KondoTakashi en-aut-sei=Kondo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyatakeNobuyuki en-aut-sei=Miyatake en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishiHiroyuki en-aut-sei=Nishi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UjikeKazuhiro en-aut-sei=Ujike en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KoumotoKiichi en-aut-sei=Koumoto en-aut-mei=Kiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NamioKeiichi en-aut-sei=Namio en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HishiiShuhei en-aut-sei=Hishii en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatayamaAkihiko en-aut-sei=Katayama en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SuzukiHiromi en-aut-sei=Suzuki en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamamotoYorimasa en-aut-sei=Yamamoto en-aut-mei=Yorimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=2 en-affil=Innoshima General Hospital kn-affil= affil-num=3 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=4 en-affil=Innoshima General Hospital kn-affil= affil-num=5 en-affil=Innoshima General Hospital kn-affil= affil-num=6 en-affil=Innoshima General Hospital kn-affil= affil-num=7 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=8 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Faculty of Social Studies, Shikokugakuin University kn-affil= affil-num=10 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=11 en-affil=Innoshima General Hospital kn-affil= en-keyword=nomogram kn-keyword=nomogram en-keyword=chronic hemodialysis kn-keyword=chronic hemodialysis en-keyword=sedentary behavior kn-keyword=sedentary behavior en-keyword=Cox proportional hazards model kn-keyword=Cox proportional hazards model en-keyword=Kaplan- Meier curve kn-keyword=Kaplan- Meier curve END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1 article-no= start-page=1 end-page=7 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=Usefulness of D-dimer Assay to Confirm the Course of Overt Venous Thromboembolism (VTE) in Cancer Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Venous thromboembolism (VTE) is a serious complication in patients with cancer. In this population, the presence of thrombi is often assessed at cancer diagnosis by measuring D-dimer levels, which have high sensitivity but low specificity for identifying VTE at this clinical time point. However, the usefulness of D-dimer measurement during anticoagulation therapy has not been fully established, despite its widespread use. In this retrospective observational study, we investigated whether D-dimer measurement during anticoagulation therapy in cancer patients could predict overt VTE at follow-up. The study included patients who underwent D-dimer testing and contrast-enhanced computed tomography between 30 and 100 days after initiation of anticoagulation therapy. Eighty-two patients were included: 60 with cancer and 22 without. The diagnostic performance of D-dimer for overt VTE was as follows: sensitivity, 85.7%; specificity, 87.2%; positive predictive value, 78.3%; and negative predictive value, 89.2%. These findings suggest that D-dimer measurement at follow-up has high sensitivity and specificity for overt VTE in cancer patients and may aid in assessing thrombotic status. Clinically, if anticoagulation therapy is continued until D-dimer levels become negative, the absence of overt VTE could be inferred without additional invasive testing. en-copyright= kn-copyright= en-aut-name=YamaokaHidenaru en-aut-sei=Yamaoka en-aut-mei=Hidenaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SarashinaToshihiro en-aut-sei=Sarashina en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MunemasaMitsuru en-aut-sei=Munemasa en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, IMS Tokyo Katsushika General Hospital kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Seisukai Kuroda Clinic kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama Rosai Hospital kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=D-dimer kn-keyword=D-dimer en-keyword=venous kn-keyword=venous en-keyword=thromboembolism kn-keyword=thromboembolism en-keyword=cancer kn-keyword=cancer 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? 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=5 cd-vols= no-issue=1 article-no= start-page=e70285 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cardiogenic cerebral infarction after Takotsubo cardiomyopathy in a patient with catatonia: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Takotsubo cardiomyopathy (TTC) is a transient cardiac condition often triggered by an emotional or physical stress. TTC usually has a benign clinical course with full recovery. However, in rare cases, TTC is complicated by cardiogenic shock, left ventricular rupture, or ventricular thrombus. We report a case of a patient with catatonia who developed TTC and subsequently experienced extensive cerebral infarction.
Case Presentation: A 71-year-old woman with no prior psychiatric history was admitted for catatonia following a suicide attempt. During hospitalization, she exhibited electrocardiography (ECG) abnormalities and elevated D-dimer levels. Transthoracic echocardiography revealed apical hypokinesis and basal hyperkinesis, consistent with TTC, along with an intraventricular thrombus. Cardiovascular CT angiography confirmed normal coronary arteries. She was diagnosed with TTC complicated by left ventricular thrombus and deep vein thrombosis. Anticoagulant therapy was initiated. Despite improvement in catatonia with lorazepam, she developed right hemiplegia and aphasia on Day 5 due to cardiogenic cerebral infarction from thromboembolism. Thrombolytic therapy was not indicated, and conservative treatment was provided. Although cardiac function normalized by Day 16, she was left with severe neurological deficits.
Conclusion: The case highlights the diagnostic challenges of TTC in non-communicative psychiatric patients and the potential for severe complications. Psychiatrists need to be aware of the development of TTC as a serious physical complication in patients with catatonia. 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=OsawaKazuhiro en-aut-sei=Osawa en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoShinji en-aut-sei=Sakamoto en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KodamaMasafumi en-aut-sei=Kodama en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center kn-affil= affil-num=4 en-affil=Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Okayama Psychiatric Medical Center kn-affil= en-keyword=catatonia kn-keyword=catatonia en-keyword=cerebral infarction kn-keyword=cerebral infarction en-keyword=depression kn-keyword=depression en-keyword=Takotsubo cardiomyopathy kn-keyword=Takotsubo cardiomyopathy en-keyword=ventricular thrombus kn-keyword=ventricular thrombus END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=4 article-no= start-page=1422 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Perioperative Ozoralizumab Management for Patients with Rheumatoid Arthritis Who Underwent Orthopaedic Surgery: A Retrospective Case Series en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Launched in Japan in 2022, ozoralizumab (OZR) is a novel, anti-tumour necrosis factor (TNF)- inhibitor for treating rheumatoid arthritis (RA) that is refractory to conventional therapies. However, there is a lack of evidence regarding its perioperative management. Methods: This retrospective case series included nine patients with RA who underwent a total of 12 either RA-related (n = 9) or unrelated (n = 3) orthopaedic procedures. We reviewed patient demographics, surgical procedures, perioperative OZR discontinuation periods, and postoperative complications. Results: The mean preoperative OZR discontinuation period was 15.8 days (range, 2?25 days). Sutures were removed at a mean of 12.8 days postoperatively (range, 11?14 days) after adequate wound healing had been confirmed. The mean total discontinuation period was 34.9 days (range, 27?43 days). No cases of surgical site infection (SSI) or delayed wound healing (DWH) were observed during a minimum follow-up period of three months. One patient experienced a disease flare before OZR was restarted. Conclusions: Preoperative OZR discontinuation for up to four weeks appeared to be safe in this cohort. These findings may assist orthopaedic surgeons in determining an appropriate perioperative discontinuation strategy for OZR that minimises SSI and DWH risk while reducing the likelihood of RA flare. en-copyright= kn-copyright= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NasuYoshihisa en-aut-sei=Nasu en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaRyozo en-aut-sei=Harada en-aut-mei=Ryozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=HoritaMasahiro en-aut-sei=Horita en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NatsumedaMasamitsu en-aut-sei=Natsumeda en-aut-mei=Masamitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaniwaShuichi en-aut-sei=Naniwa en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Locomotive Pain Center, Faculty of Medical Development Field, Okayama University kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama City Hospital kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Kurashiki Sweet Hospital kn-affil= affil-num=4 en-affil=Locomotive Pain Center, Faculty of Medical Development Field, Okayama University kn-affil= affil-num=5 en-affil=Locomotive Pain Center, Faculty of Medical Development Field, Okayama University kn-affil= affil-num=6 en-affil=Rheumatic Disease Center, Mabi Memorial Hospital kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=delayed wound healing kn-keyword=delayed wound healing en-keyword=discontinuation kn-keyword=discontinuation en-keyword=ozoralizumab kn-keyword=ozoralizumab en-keyword=orthopaedic surgery kn-keyword=orthopaedic surgery en-keyword=perioperative management kn-keyword=perioperative management en-keyword=rheumatoid arthritis kn-keyword=rheumatoid arthritis en-keyword=surgical site infection kn-keyword=surgical site infection 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=20260210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Starch Synthase 3 isoforms are essential for normal starch granule initiation in wheat endosperm en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=DingJinjin en-aut-sei=Ding en-aut-mei=Jinjin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FahyBrendan en-aut-sei=Fahy en-aut-mei=Brendan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=JiangQiantao en-aut-sei=Jiang en-aut-mei=Qiantao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SeungDavid en-aut-sei=Seung en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=John Innes Centre, Norwich Research Park kn-affil= affil-num=2 en-affil=John Innes Centre, Norwich Research Park kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Triticeae Research Institute, Sichuan Agricultural University kn-affil= affil-num=5 en-affil=John Innes Centre, Norwich Research Park kn-affil= en-keyword=resistant starch kn-keyword=resistant starch en-keyword=starch kn-keyword=starch en-keyword=starch granule kn-keyword=starch granule en-keyword=starch synthase kn-keyword=starch synthase en-keyword=wheat kn-keyword=wheat 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 -smooth muscle actin (-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=14 cd-vols= no-issue=1 article-no= start-page=9 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Influence of Fluidic Flow Stress on the Development of the Secondary Palate en-subtitle= kn-subtitle= en-abstract= kn-abstract=Craniofacial development is orchestrated by a finely regulated interplay of numerous genes and signaling pathways. Palatogenesis proceeds through a complex, stepwise process, in which endogenous mechanical stresses within tissues have been implicated. However, the impact of exogenous fluidic flow mechanical stress derived from maternal movement on palatal development remains unclear. In this study, we investigated the effect of exogenous fluidic flow mechanical stress on palatal morphogenesis, focusing on the horizontal outgrowth of palatal shelves after elevation. Palatal tissues dissected from mouse embryos were subjected to organ culture with or without mechanical loading (loaded and unloaded groups, respectively). Stress magnitude was quantified by calculating wave energy, and morphometric and molecular analyses were performed. Compared with the unloaded group, palatal shelves in the loaded group showed significant increases in thickness and volume, accompanied by enhanced cell proliferation, nuclear translocation of YAP and -catenin, and upregulation of the osteogenic markers Osterix and Osteocalcin. No significant difference in apoptosis was observed. These findings indicate that exogenous mechanical stress promotes cell proliferation and osteogenic differentiation through the Hippo and WNT/-catenin pathways in palate explants. Our results suggest that moderate maternal movement-induced mechanical stress contributes to normal palatogenesis, providing new insights into the mechanisms underlying cleft palate. en-copyright= kn-copyright= en-aut-name=NagataMasayo en-aut-sei=Nagata en-aut-mei=Masayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayanoSatoru en-aut-sei=Hayano en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=KosamiTakahiro en-aut-sei=Kosami en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Orthodontics, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Orthodontics, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=mechanical stress kn-keyword=mechanical stress en-keyword=palatal development kn-keyword=palatal development en-keyword=-catenin kn-keyword=-catenin en-keyword=YAP kn-keyword=YAP END start-ver=1.4 cd-journal=joma no-vol=178 cd-vols= no-issue=1 article-no= start-page=e70775 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=Reactive Carbonyl Species Mediate Isothiocyanate Signaling Pathway in Arabidopsis thaliana Guard Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Our previous results demonstrated that depletion of glutathione (GSH) rather than elevation of levels of reactive oxygen species (ROS) is highly correlated with the decrease in stomatal aperture induced by isothiocyanates (ITCs), although ROS is considered a key second messenger in stomatal closure, suggesting that another signal component regulates stomatal apertures along with GSH depletion. This study, using Arabidopsis, clarified that reactive carbonyl species (RCS), especially acrolein and 4-hydroxy-(E)-2-nonenal, are determinants of stomatal aperture responses to ITCs. All tested ITCs, allyl isothiocyanate (AITC), sulforaphane (SFN), benzyl isothiocyanate (BITC), and phenethyl isothiocyanate (PEITC), significantly induced stomatal closure, which was inhibited by the RCS scavengers, carnosine and pyridoxamine. The RCS scavengers suppressed ITC-induced depletion of GSH but not elevation of ROS levels. All tested ITCs (AITC, SFN, BITC, and PEITC) increased levels of RCS and non-RCS aldehydes in the epidermal tissues. However, acrolein, 4-hydroxy-(E)-2-nonenal, crotonaldehyde, and (E)-2-pentenal induced stomatal closure at 10 and 100?M, whereas propionaldehyde, butyraldehyde, and n-pentanal did not at concentrations up to 100?M. Acrolein and 4-hydroxy-(E)-2-nonenal more effectively induced stomatal closure and GSH depletion than crotonaldehyde and (E)-2-pentenal did. The contents of RCS were more strongly correlated with GSH levels and stomatal closure than with ROS levels. These results suggest that RCS, especially acrolein and 4-hydroxy-(E)-2-nonenal, acts as key regulators of stomatal closure in guard cells in response to ITCs. en-copyright= kn-copyright= en-aut-name=FarzanaSumaiya en-aut-sei=Farzana en-aut-mei=Sumaiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IslamMd. Moshiul en-aut-sei=Islam en-aut-mei=Md. Moshiul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraToshiyuki en-aut-sei=Nakamura en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=MunemasaShintaro en-aut-sei=Munemasa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ManoJun'ichi en-aut-sei=Mano en-aut-mei=Jun'ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MurataYoshiyuki en-aut-sei=Murata en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=Science Research Center, Yamaguchi University kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=arabidopsis kn-keyword=arabidopsis en-keyword=GSH depletion kn-keyword=GSH depletion en-keyword=isothiocyanate kn-keyword=isothiocyanate en-keyword=reactive carbonyl species kn-keyword=reactive carbonyl species en-keyword=reactive oxygen species kn-keyword=reactive oxygen species 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 ?m 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 ?m) in AM specimens, along with step-like irregularities (~40 ?m) 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= cd-vols= no-issue= article-no= start-page= 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=Does Human Depopulation Reduce Resource Consumption??Evidence from Anthropocene Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Humanityfs deepening strain on Earth systems has sparked widespread discussion of an gAnthropocene crisis,h often attributed to overpopulation. This raises the question: if overpopulation underpins the crisis, does its resolution lie in depopulation? Here, we examine the effects of Japanfs ongoing depopulation on the nexus of population, economy, cropland use, food, water, and energy. We take a systematic Bayesian approach to examine changes in the strength and direction of causality among these variables and explore plausible future pathways under Shared Socioeconomic Pathway (SSP) scenarios. We find that, while depopulation has led to reductions in resource demand, notably for water and energy, impacts on the food system are more complex due to interdependencies with economic and other factors beyond population change. In conclusion, we argue that it will take longer than predicted for depopulation dividends to materialize at a scale that could meaningfully contribute to addressing the crisis, and that proactive efforts to reshape consumption patterns and restructure economic systems, from a model predicated on perpetual growth to one oriented toward sufficiency, are necessary to capitalize on the potential dividends offered by this demographic shift. en-copyright= kn-copyright= en-aut-name=BarrahmouneAnass en-aut-sei=Barrahmoune en-aut-mei=Anass kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatanlePeter en-aut-sei=Matanle en-aut-mei=Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimJiyoung en-aut-sei=Kim en-aut-mei=Jiyoung kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Humanities and Social Sciences, Faculty of Economics, Okayama University kn-affil= affil-num=2 en-affil=School of East Asian Studies, The University of Sheffield kn-affil= affil-num=3 en-affil=Graduate School of Humanities and Social Sciences, Faculty of Economics, Okayama University kn-affil= en-keyword=Anthropocene crisis kn-keyword=Anthropocene crisis en-keyword=Depopulation dividend kn-keyword=Depopulation dividend en-keyword=Population kn-keyword=Population en-keyword=Overpopulation kn-keyword=Overpopulation en-keyword=Resource nexus kn-keyword=Resource nexus en-keyword=Bayesian analysis kn-keyword=Bayesian analysis 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=70 cd-vols= no-issue=1 article-no= start-page=355 end-page=365 dt-received= dt-revised= dt-accepted= dt-pub-year=2006 dt-pub=2006 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis of 6- and 7-(1,2,3-Trihydroxy-1,2-O-isopropylidenepropyl)pteridines and Deoxygenation of Their 3f-Hydroxy Groups en-subtitle= kn-subtitle= en-abstract= kn-abstract=Treatment of 3,4-O-isopropylidene-L-threo-pentos-2-ulose (7) with 5,6-diamino-1,3-dimethyluracil (8) afforded 1,3-dimethyl-6-[(1R,2S)-1,2,3-trihydroxy-1,2-O-isopropylidenepropyl]lumazine (9a) and its 7-substituted isomer (9b). Deoxygenation of 3f-hydroxy groups of 9a,b was investigated in connection with a practical transformation of neopterin into biopterin. en-copyright= kn-copyright= en-aut-name=HanayaTadashi en-aut-sei=Hanaya en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakayamaDaisuke en-aut-sei=Takayama en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoHiroshi en-aut-sei=Yamamoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry, Faculty of Science, Okayama University 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=2026 dt-pub=20260202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pediatric autologous peripheral blood stem cell collection without heparin using a highly concentrated sodium citrate anticoagulant: A retrospective comparison with standard ACD-A en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Heparin combined with sodium citrate has been used in leukocytapheresis for pediatric patients. Since 2022, we have performed leukocytapheresis using a highly concentrated sodium citrate solution (HSC, 5.32%) instead of acid citrate dextrose solution A (ACD-A). We conducted this study to determine whether HSC use reduces run time and the total amount of anticoagulant solution in children.
Study Design and Methods: We retrospectively analyzed data from consecutive autologous peripheral blood stem cell harvests (auto-PBSCHs) between June 2012 and May 2025, including patient characteristics, mobilization methods, protocol used, anticoagulant type, run time, total anticoagulant solution volume, and collection efficiency.
Results: Auto-PBSCH was performed using the mononuclear cell collection (MNC) protocol in 28 procedures and the continuous MNC protocol in 20 procedures. ACD-A was used in 35 procedures and HSC in 13. The run time was significantly shorter (204 [range, 117?302] vs. 157?min [range, 103?227], p?=?.02) in the HSC group and also confirmed in multivariable regression analysis (coefficient, ?55.6; 95% confidence interval, ?106.2 to ?5.04; p?=?.03). In a subgroup analysis of cMNC procedures, CD34+ collection efficiency showed a strong negative correlation with the proportion of run time devoted to establishing the initial interface (r?=??.73, p?=?.0003).
Conclusion: Delays in establishing the initial interface can reduce the duration of the effective MNC collection phase and may negatively affect collection efficiency. Careful attention to the initial interface phase is therefore warranted when using HSC. en-copyright= kn-copyright= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WashioKana en-aut-sei=Washio en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IkeuchiKazuhiro en-aut-sei=Ikeuchi en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimonoJoji en-aut-sei=Shimono en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MurakamiHiroyuki en-aut-sei=Murakami en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=9 ORCID= affil-num=1 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology, Okayama University Hospital kn-affil= en-keyword=acid citrate dextrose solution kn-keyword=acid citrate dextrose solution en-keyword=autologous kn-keyword=autologous en-keyword=continuous mononuclear cell collection kn-keyword=continuous mononuclear cell collection en-keyword=highly concentrated sodium kn-keyword=highly concentrated sodium en-keyword=pediatric kn-keyword=pediatric en-keyword=peripheral blood stem cells kn-keyword=peripheral blood stem cells END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue= article-no= start-page= 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=Clinical efficacy and safety of endoscopic ultrasound-guided ablation therapies for pancreatic neuroendocrine tumors: a systematic review and meta-analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Pancreatic neuroendocrine tumors (pNETs) are rare; however, they are increasingly being detected. Although surgical resection remains the standard treatment, its invasiveness has prompted interest in less invasive alternatives, particularly for small non-functional pNETs (NF-pNETs) and insulinomas.
Objectives: To evaluate the clinical efficacy and safety of endoscopic ultrasound-guided ethanol injection (EUS-EI) and radiofrequency ablation (EUS-RFA) for pNETs.
Design: A systematic review and meta-analysis.
Data sources and methods: A literature search of PubMed, MEDLINE, and Google Scholar was conducted (April 2005?April 2025). Studies were eligible if they reported clinical outcomes of EUS-EI or EUS-RFA in adult patients with insulinomas or NF-pNETs. The primary endpoints were clinical success (short-term symptom resolution or radiological response) and adverse event (AE) rates. Data were pooled using a random-effects model.
Results: Twenty-six studies were included in the meta-analysis. For insulinomas, the pooled clinical success rate was 77% (95% confidence interval (CI), 59?88) for EUS-EI and 95% (95% CI, 89?97) for EUS-RFA. The pooled incidence of total AEs was 32% (95% CI, 17?51) for EUS-EI and 25% (95% CI, 15?39) for EUS-RFA. For NF-pNETs, the pooled clinical success rates were 76% (95% CI, 54?90) for EUS-EI and 85% (95% CI, 74?92) for EUS-RFA, and the pooled incidence of total AEs was 27% (95% CI, 20?35) and 26% (95% CI, 17?38), respectively. The most common moderate or severe AEs were pancreatitis in 12 patients (7.6%) after EUS-EI, and pancreatic fluid collection in 4 patients (1.9%) and pancreatic duct stricture in 3 patients (1.4%) after EUS-RFA. One fatal case occurred in a 97-year-old patient following EUS-RFA.
Conclusion: Both EUS-EI and EUS-RFA are effective, relatively safe, and minimally invasive treatment options for pNETs. However, severe AE can occur, and careful patient selection and treatment indication are essential.
Trial registration: Not registered. en-copyright= kn-copyright= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakeuchiYasuto en-aut-sei=Takeuchi en-aut-mei=Yasuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=ablation techniques kn-keyword=ablation techniques en-keyword=endoscopic ultrasonography kn-keyword=endoscopic ultrasonography en-keyword=ethanol kn-keyword=ethanol en-keyword=pancreatic neuroendocrine tumors kn-keyword=pancreatic neuroendocrine tumors en-keyword=radiofrequency ablation kn-keyword=radiofrequency ablation END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=1 article-no= start-page=283 end-page=294 dt-received= dt-revised= dt-accepted= dt-pub-year=2006 dt-pub=2006 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis of Functionalized Phospholane Oxides and Phosphorinane Oxides from 1,4- and 1,5-Di-O-Mesyloxy Compounds en-subtitle= kn-subtitle= en-abstract= kn-abstract=Treatment of 1,4-di-O-mesyl-2,3-di-O-methyl-L-threitol (8b) with phenylphosphine in the presence of sodium hydride in DMSO, followed by the action of hydrogen peroxide, afforded 3,4-dimethoxy-1-phenylphospholane 1- oxide (7), while the same treatment of 1,5-di-O-mesyl-2,3,4-tri-O-methyl-meso- xylitol (11b) provided 2,3,4-trimethoxy-1-phenylphosphorinane 1-oxide (14). en-copyright= kn-copyright= en-aut-name=HanayaTadashi en-aut-sei=Hanaya en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Sch?rrleKarsten en-aut-sei=Sch?rrle en-aut-mei=Karsten kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoHiroshi en-aut-sei=Yamamoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue=1 article-no= start-page=19 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260116 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mycobacterium mageritense-associated refractory cutaneous infection and lymphadenitis in an immunocompetent adult: insights from genomic sequencing en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Nontuberculous mycobacteria are increasingly recognized as causes of chronic and refractory skin and soft tissue infections, even in individuals without immunodeficiency. Among them, Mycobacterium mageritense is a rare, rapidly growing species that can lead to persistent lesions requiring prolonged antimicrobial therapy. Reports of M. mageritense infections involving both the skin and regional lymph nodes are limited, and this case adds new clinical and genomic insights.
Case presentation A 48-year-old previously healthy man presented with a slowly enlarging cutaneous lesion on his lower leg and ipsilateral inguinal lymphadenitis. Empirical antibacterial therapy with -lactams and macrolides was ineffective. Wound cultures subsequently grew M. mageritense, confirmed by whole-genome sequencing. Several antimicrobial regimens were attempted, and the final successful therapy consisted of oral levofloxacin and minocycline for 4 months, leading to complete clinical resolution. Genomic analysis identified resistance-related genes, including erm(40), aac(2)-Ib, tet(V), and RbpA, although in vitro minimum inhibitory concentrations showed variable susceptibility. Phylogenetic comparison revealed that the isolate was closely related to previously reported M. mageritense strains from Japan.
Conclusions This case demonstrates that M. mageritense can cause cutaneous infection with secondary lymphadenitis in an immunocompetent host. Accurate species identification using molecular or genomic methods and selection of appropriate combination antibiotic therapy based on susceptibility testing are crucial for successful management of such infections. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KawakamiYoshio en-aut-sei=Kawakami en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuuraYoshiko en-aut-sei=Matsuura en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugiharaSatoru en-aut-sei=Sugihara en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MuenrayaPoowadon en-aut-sei=Muenraya en-aut-mei=Poowadon 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 Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Konohana Dermatology Clinic kn-affil= affil-num=5 en-affil=Department of Dermatology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Dermatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Genome sequence kn-keyword=Genome sequence en-keyword=Lymphadenitis kn-keyword=Lymphadenitis en-keyword=Mycobacterium mageritense kn-keyword=Mycobacterium mageritense en-keyword=Skin and soft tissue infections kn-keyword=Skin and soft tissue infections en-keyword=Rapidly growing mycobacteria kn-keyword=Rapidly growing mycobacteria 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=20260119 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A retrospective cohort study comparing periodontal regeneration using fibroblast growth factor]2 versus autologous bone graft en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Fibroblast growth factor-2 (FGF-2) is a novel agent utilized in periodontal regeneration therapy. However, its clinical efficacy compared with autologous bone graft (ABG), a long-established treatment, remains unclear. This study aimed to compare the clinical outcomes of FGF-2 and ABG and to assess the impact of patient background factors on outcomes when using FGF-2.
Methods: We collected the subjects from January 2013 to September 2023. Clinical outcomes included the vertical bone defect improvement rate (VBDIR) and the probing pocket depth improvement (PPDI). Clinical outcomes between the two groups were compared using analysis of covariance (ANCOVA), adjusting for age, sex, smoking history, and hypertension. Additionally, a multilevel linear analysis was performed to assess factors influencing outcomes in FGF-2.
Results: A total of 180 sites from 141 patients (FGF-2: 150 sites; ABG: 30 sites) were evaluated. Both VBDIR and PPDI significantly improved postoperatively in both groups. There were no significant differences in clinical outcomes between FGF-2 and ABG. In FGF-2, smoking history was positively associated, while the preoperative bone defect angle (BDA) was negatively associated with clinical outcomes.
Conclusions: FGF-2 might exhibit clinical outcomes comparable to those of ABG, suggesting it is a clinically viable alternative for vertical bone defects. When using FGF-2, patient-specific factors such as smoking history and preoperative BDA should be considered carefully.
The name in the trial registry: A survey of clinical practice and evaluation of treatment outcomes of periodontal regenerative therapy using REGROTH at Okayama University Hospital en-copyright= kn-copyright= en-aut-name=MatsumotoToshiki en-aut-sei=Matsumoto en-aut-mei=Toshiki 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=Ito]ShinodaYuki en-aut-sei=Ito]Shinoda en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoMai en-aut-sei=Sakamoto en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=NonomuraYasuki en-aut-sei=Nonomura en-aut-mei=Yasuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IdeguchiHidetaka en-aut-sei=Ideguchi en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkuboKeisuke en-aut-sei=Okubo en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=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=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=autologous bone graft kn-keyword=autologous bone graft en-keyword=fibroblast growth factor-2 kn-keyword=fibroblast growth factor-2 en-keyword=periodontal pocket kn-keyword=periodontal pocket en-keyword=periodontal regeneration kn-keyword=periodontal regeneration en-keyword=periodontitis kn-keyword=periodontitis en-keyword=vertical bone defect kn-keyword=vertical bone defect END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=26 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Osimertinib inhibits the MYLK4-mediated phosphorylation of CDKAL1 to suppress stemness and chemoresistance in rhabdomyosarcoma en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ItanoTakuto en-aut-sei=Itano en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HuangRongsheng en-aut-sei=Huang en-aut-mei=Rongsheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=2026 cd-vols= no-issue=1 article-no= start-page=7874254 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=Experimental Analysis of Automatic Discrimination Performance Between Simulated Bruxism and Non]Bruxism Under Conscious Conditions Using Electromyography and Machine Learning en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: This study aimed to evaluate the potential use of machine learning to automatically classify electromyography (EMG) data into bruxism simulated movement with tooth contact (BMwTC), bruxism simulated movement without tooth contact (BMwoTC), and non-bruxism movement (non-BM).
Methods: Twelve eligible healthy participants (female/male: 2/10, mean age: 35.3?}?8.4?years) were asked to perform the simulated movements (all the tasks were performed five times for 5?s each with a 30-s rest interval). The electrodes were placed on the masseter, infrahyoid, inframandibular, and chin muscles. A sound sensor was placed adjacent to the masseter. The EMG and sound data were sampled at 1 and 44.1?kHz, respectively. Single- and multi-stream hidden Markov models (HMMs) were used to automatically discriminate the tested behavior from the others using a hamming window with 100?ms and shift length of 50?ms. The leave-one-out method was used for training and testing the model, with data from 11 participants used for training and one for testing. Each participant was evaluated, and the final performance was measured by averaging the results of 12 classification trials. The validity of the discrimination was assessed by calculating the harmony mean values using six EMG signals and the sound data.
Results: The masseter EMG demonstrated significantly higher discrimination accuracy in the single-stream model (p? < 0.05, One-way ANOVA, Tukey HDS). The multi-stream model also demonstrated higher accuracy; however, no significant difference was observed. Notably, the accuracy of BMwoTC was less than 0.5.
Conclusion: The machine-learning-based discriminative system accurately discriminates BMwTC from non-BM using masseter EMG. en-copyright= kn-copyright= en-aut-name=MinakuchiHajime en-aut-sei=Minakuchi en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagasakiMitsuhiro en-aut-sei=Nagasaki en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=??nhL?c Ho?ng en-aut-sei=??nh en-aut-mei=L?c Ho?ng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MikiHaruna en-aut-sei=Miki en-aut-mei=Haruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OmoriKo en-aut-sei=Omori en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishimuraTazuko en-aut-sei=Nishimura en-aut-mei=Tazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KubokiTakuo en-aut-sei=Kuboki en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MinematsuNobuaki en-aut-sei=Minematsu en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Electrical Engineering and Information Systems, Graduate School of Engineering, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Electrical Engineering and Information Systems, Graduate School of Engineering, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Electrical Engineering and Information Systems, Graduate School of Engineering, The University of Tokyo kn-affil= en-keyword=bruxism kn-keyword=bruxism en-keyword=dentistry kn-keyword=dentistry en-keyword=electromyography kn-keyword=electromyography en-keyword=EMG discrimination kn-keyword=EMG discrimination en-keyword=machine learning kn-keyword=machine learning 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=20260120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SPRED2 suppresses the stemness of hepatocellular carcinoma through the p53/miR-506-3p/KLF4 pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: We previously reported that endogenous Sprouty-related, EVH1 domain-containing protein 2 (SPRED2), an inhibitor of the Ras/Raf/ERK-MAPK pathway, controls hepatocellular carcinoma (HCC) cell stemness by downregulating the expression of pluripotency factors, such as Nanog, c-Myc, and KLF4, in an ERK-dependent fashion. However, the exact mechanisms by which SPRED2 regulates HCC cell stemness have not been established.
Methods: Three human HCC cell lines [HepG2 (parental and SPRED2-deficient), HLE, and Hep3B] were used. Cells were transfected to downregulate or overexpress proteins. Western blot and RT-qPCR were used to evaluate the level of protein and mRNA expression. Co-immunoprecipitation and ChIP-qPCR were used to examine protein-protein interactions and the activation of gene transcription. Clinical HCC tissues were also used to validate in vitro data.
Results: KLF4 was identified as the major pluripotency factor responsible for SPRED2-mediated downregulation of HCC cell stemness and KLF4 expression was regulated by miR-506-3p. SPRED2 formed a protein complex with the tumor suppressor (p53) and upregulated miR-506 gene transcription by binding to the promoter region, resulting in subsequent downregulation of KLF4 mRNA expression. There was a negative correlation between KLF4 expression and miR-506-3p and a positive correlation between miR-506-3p expression and SPRED2 in human HCC samples, highlighting the relevance of the study findings.
Conclusions: The current study revealed a novel SPRED2/p53/miR-506-3p/KLF4 axis through which SPRED2 contributes to the suppression of HCC cell stemness and provides a potential new target to prevent HCC progression. en-copyright= kn-copyright= en-aut-name=GaoTong en-aut-sei=Gao en-aut-mei=Tong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoSachio en-aut-sei=Ito en-aut-mei=Sachio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Moh-Moh-AungAye en-aut-sei=Moh-Moh-Aung en-aut-mei=Aye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangTianyi en-aut-sei=Wang en-aut-mei=Tianyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=SPRED2 kn-keyword=SPRED2 en-keyword=p53 kn-keyword=p53 en-keyword=KLF4 kn-keyword=KLF4 en-keyword=miR-506-3p kn-keyword=miR-506-3p en-keyword=stemness kn-keyword=stemness END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue= article-no= start-page=105566 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A semi-quantitative archaeothermometer based on feldspar and volcanic glass compositions in ancient ceramics from the Kibi region, Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this study, we analyzed the chemical compositions of feldspar and volcanic glass clasts in haniwa from kofuns and Sue ware from the Sabukaze kiln site, both in the Kibi region, southwestern Japan, to estimate the thermal conditions of ceramic firing in the 5th?8th centuries CE. Based on the coexistence of molten and unmolten feldspar rims, the solidus temperatures were estimated at ? 1050C?1150C for haniwa and ? 1150C?1200C for Sue ware. Volcanic glass compositions changed systematically during firing, showing increases in K2O and decreases in Na2O. From these observations, we propose a semi-quantitative archaeothermometer using variations in the K/Na molar ratio of volcanic glass within a ceramic matrix. This approach can be applied to investigate the development of kiln-firing in the Kibi region, the existence of haniwa potters employing different firing methods, variation in heat input for producing Sue vessels of differing sizes or functions, and temperature-controlled practices in Sue ware production. en-copyright= kn-copyright= en-aut-name=NozakaToshio en-aut-sei=Nozaka en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhbayashiNaoya en-aut-sei=Ohbayashi en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TodaYuki en-aut-sei=Toda en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AnamiTaiji en-aut-sei=Anami en-aut-mei=Taiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugiuraKanako en-aut-sei=Sugiura en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NozakiTakahiro en-aut-sei=Nozaki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimuraOsamu en-aut-sei=Kimura en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumotoNaoko en-aut-sei=Matsumoto en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SeikeAkira en-aut-sei=Seike en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Archaeology, Okayama University kn-affil= affil-num=6 en-affil=Research Institute for the Dynamics of Civilizations, Okayama University kn-affil= affil-num=7 en-affil=Research Institute for the Dynamics of Civilizations, Okayama University kn-affil= affil-num=8 en-affil=Research Institute for the Dynamics of Civilizations, Okayama University kn-affil= affil-num=9 en-affil=Department of Archaeology, Okayama University kn-affil= en-keyword=Haniwa kn-keyword=Haniwa en-keyword=Sue ware kn-keyword=Sue ware en-keyword=Firing temperature kn-keyword=Firing temperature en-keyword=Kibi kn-keyword=Kibi en-keyword=Japan kn-keyword=Japan END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=12 article-no= start-page=e095428 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=Effectiveness of education programme to increase competency of health cadres in Indonesia: a cluster non-randomised controlled trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives Health cadres, who assist midwives in supporting pregnant women in community settings, need to enhance their competencies in identifying risk factors and referring high-risk pregnant women to midwives for further care. Since the capabilities of these health cadres are influenced by maternal complications, an educational programme was implemented to strengthen their skills. Therefore, this study aimed to evaluate the competency of health cadres by providing a researcher-developed educational programme.
Design An open-label, cluster non-randomised controlled trial.
Setting and participants Health cadres with at least 1 year of work experience were recruited at six public health centres (PHCs) in Banjarnegara Regency, Indonesia.
Interventions Six PHCs were selected and allocated into intervention group (IG=3 PHCs) and control group (CG=3 PHCs) groups. A total of 133 female health cadres were enrolled across the selected PHCs. At each PHC, a systematic random sampling method was used to select the participants. The researchers and health professionals provided a 3-week period of theoretical and scenario-based simulations to the IG, while the CG received no education.
Outcome measures Researcher-developed questionnaires and checklists were used to assess the knowledge, skills (health assessment, communication, attitude) and confidence. The primary endpoint was competency, a total score of knowledge and skills. The outcome domains were compared between the two groups, and a linear mixed-effect model was used to account for cluster-level variation.
Results A total of 130 (97.7%) completed the study (IG:64, CG:66). The competency score showed significant improvement at endline (CG=49.5?and IG=52.5; p=0.002). The median scores for health assessment skills (CG=12?vs IG=14; p<0.001) and communication skills (CG=7?vs IG=8; p<0.001) were increased in the IG compared with the CG. Mixed-effect model indicated that groups ( (95%?CI) 2.49 (0.57 to 4.41), p=0.012), baseline knowledge ((95%?CI) 0.73 (0.54 to 0.92), p<0.001) and midline health assessment skills ( (95%?CI) 0.54 (0.25 to 0.82), p<0.001) were significant positive predictors, while age was negatively associated with competency ( (95%?CI) ?0.20 (?0.30 to ?0.10), p<0.001)).
Conclusion Education effectively increased the competency of health cadres. A well-structured education programme is necessary for health cadres to improve and maintain their competencies in monitoring high-risk pregnant women.
Trial registration number NCT06134518. en-copyright= kn-copyright= en-aut-name=SulistyoriniDewie en-aut-sei=Sulistyorini en-aut-mei=Dewie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HuqK A T M Ehsanul en-aut-sei=Huq en-aut-mei=K A T M Ehsanul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BabaitaAbdulfatai Olamilekan en-aut-sei=Babaita en-aut-mei=Abdulfatai Olamilekan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AiveySadia A en-aut-sei=Aivey en-aut-mei=Sadia A kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HuiyingGao en-aut-sei=Huiying en-aut-mei=Gao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KazawaKana en-aut-sei=Kazawa en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FukushimaYasuko en-aut-sei=Fukushima en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KakoMayumi en-aut-sei=Kako en-aut-mei=Mayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoriyamaMichiko en-aut-sei=Moriyama en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=2 en-affil=Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=3 en-affil=Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=4 en-affil=Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=5 en-affil=Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=6 en-affil=Faculty of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=8 en-affil=Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=9 en-affil=Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= 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=131 cd-vols= no-issue=1 article-no= start-page=e2025JB033390 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=Electrical Conductivity of Carbonatite Melts to 20?GPa: Constraints on Partial Melting Atop the 410]km Discontinuity and in the Lower Mantle Transition Zone en-subtitle= kn-subtitle= en-abstract= kn-abstract=Deep-origin carbonatite melts are considered to be the products of partial-melting of the oceanic crust in the subduction zones. In this study, we conducted electrical conductivity (EC) measurements on two samples, the composition of which resemble the partial-melting products atop the 410-km discontinuity and in the lower part of the transition zone. The EC of carbonatite melts was investigated using impedance spectroscopy combined with a multi-anvil press up to 20 GPa. Pressure has a great effect on the EC of the carbonatite melts. While the EC dropped overall by 0.6 log unit from 3 to 20 GPa for varying compositions, the pressure effect becomes weaker above 10 GPa. The Hashin-Shtrikman mixing model indicates that melt fraction of 0?0.3 vol% is necessary to account for the EC atop the 410-km discontinuity beneath NE China, north Philippine Sea, north Pacific, and Australian craton. However, this value soars to 1?4.5 vol% for the lower part of the transition zone in the same regions, and further increases to 3.7?7.3 vol% for cold subduction regions if the slab surface temperature is 300 K lower. The difference in the needed melt fraction at different depths implies that the magnitude of partial melting is much larger in the lower part of the mantle transition zone, and it is thus likely to be the main barrier to the recycled carbonates towards the deep interior. 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=ZhuJintao en-aut-sei=Zhu en-aut-mei=Jintao 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=YoshinoTakashi en-aut-sei=Yoshino en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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, University of Chicago kn-affil= affil-num=4 en-affil=Institute for Planetary Materials, Okayama University kn-affil= en-keyword=carbon kn-keyword=carbon en-keyword=carbonatite melts kn-keyword=carbonatite melts en-keyword=electrical conductivity kn-keyword=electrical conductivity en-keyword=impedance spectroscopy kn-keyword=impedance spectroscopy en-keyword=multi-anvil press kn-keyword=multi-anvil press END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=12 article-no= start-page=110594 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endoscopic features of oral and pharyngolaryngeal papillomas and their role in distinguishing squamous cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND
Oral and pharyngolaryngeal papillomas are occasionally detected during esophagogastroduodenoscopy. However, their endoscopic features have not been sufficiently investigated.
AIM
To distinguish oral and pharyngolaryngeal papillomas from elevated squamous carcinomas, this study examined their endoscopic features.
METHODS
Forty-seven patients with oral or pharyngeal papilloma participated in this study. The endoscopic characteristics of papillomas were identified by focusing on narrowband and blue laser imaging representations.
RESULTS
Papillomas were classified into three patterns based on their endoscopic features: Salmon roe-like polyps, polyps without capillary transparency, and pinecone-like polyps, with salmon roe-like polyps most prevalent (48.9%). We subsequently analyzed features differentiating papillomas and squamous cell carcinomas in the same region and found that squamous cell carcinomas exhibited at least one of the following three features: Uneven or absent lobulated structure, irregular morphology of capillaries, and coexistence of flat lesions. In contrast, papillomas displayed a uniform lobulated structure, homogeneous or non-visible capillaries, and an absence of flat components. When any of these characteristics were present, two endoscopic specialists evaluated the lesions for the diagnosis of squamous cell carcinoma, with sensitivities of 100% and 97.6% and specificities of 68.9% and 93.3%.
CONCLUSION
Understanding distinct endoscopic patterns of oropharyngeal papillomas and squamous cell carcinomas provides valuable guidance to endoscopists performing esophagogastroduodenoscopy. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=HamadaKenta en-aut-sei=Hamada en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Esophagogastroduodenoscopy kn-keyword=Esophagogastroduodenoscopy en-keyword=Human papillomavirus kn-keyword=Human papillomavirus en-keyword=Laryngeal polyp kn-keyword=Laryngeal polyp en-keyword=Papilloma kn-keyword=Papilloma en-keyword=Pharyngeal polyp kn-keyword=Pharyngeal polyp END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=1786 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251221 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Salivary short chain fatty acids serve as biomarkers of periodontal inflammatory burden en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontitis is a chronic inflammatory condition associated with systemic diseases. Early detection and intervention are crucial; however, conventional diagnostic methods require specialized dental procedures. Therefore, we aimed to develop a noninvasive saliva-based screening method that can be easily performed outside dental clinics. This cross-sectional pilot study evaluated three periodontal indices?probing depth, Periodontal Inflamed Surface Area (PISA), and periodontal epithelial surface area?in relation to short-chain fatty acids (SCFAs) and bacterial profiles in the saliva. Saliva samples collected during the day exhibited stronger correlations with periodontal indices than waking time samples, demonstrating a significant association with periodontal pathogens, protease activity, and elevated levels of butyric acid. The diagnostic thresholds for PISA were 300 mm2 and 600 mm2. Multivariate logistic regression and likelihood ratio analyses identified the combination of enzymatic SCFA markers and dipstick-based occult blood or leukocyte detection as a promising biomarker pair. Combining enzymatic SCFA markers with occult blood demonstrated a positive likelihood ratio of 3.4 and a negative likelihood ratio of 0.19 for PISA???600 mm2, with a post-test probability of 77%, sensitivity of 86%, and specificity of 75%. These findings suggest that combining salivary enzymatic and dipstick-based biomarkers provides a simple, cost-effective, and moderately informative screening strategy for periodontitis. en-copyright= kn-copyright= 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=1 ORCID= en-aut-name=ShirahaseYasushi en-aut-sei=Shirahase en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaToshiyuki en-aut-sei=Yoshida en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KonoMari en-aut-sei=Kono en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToyaNaoki en-aut-sei=Toya en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KonishiKenji en-aut-sei=Konishi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= affil-num=1 en-affil=Division of Periodontics and Endodontics, Department of Dentistry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Sysmex Corporation kn-affil= affil-num=3 en-affil=Sysmex Corporation kn-affil= affil-num=4 en-affil=Sysmex Corporation kn-affil= affil-num=5 en-affil=Sysmex Corporation kn-affil= affil-num=6 en-affil=Present address: Diagnostics Division, IVD Enzyme Department, Nagase Diagnostics kn-affil= affil-num=7 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Periodontitis kn-keyword=Periodontitis en-keyword=Screening kn-keyword=Screening en-keyword=Saliva kn-keyword=Saliva en-keyword=Short-chain fatty acid kn-keyword=Short-chain fatty acid en-keyword=Periodontal inflamed surface area kn-keyword=Periodontal inflamed surface area en-keyword=Crosssectional studies kn-keyword=Crosssectional studies END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=ofaf790 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251223 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Candida Care Bundle Compliance on the Prognosis of Patients With Candidemia: A Multicenter Retrospective Cohort Study With Propensity Score Matching Analysis (2016?2023) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background. Candidemia is a life-threatening infection with high mortality, and appropriate management is essential to improve patient outcomes. The Candida Care Bundle aims to standardize hospital management for patients with candidemia and reduce mortality.
Methods. This retrospective multicenter cohort study included candidemia cases from 9 hospitals in Japan between 2016 and 2023. Compliance to the Candida Care Bundle was evaluated based on 5 elements: central venous catheter removal within 24?hours, appropriate antifungal therapy, ophthalmologic examination, follow-up blood cultures, and antifungal treatment for ?2 weeks after clearance. Patients were categorized into high (4?5 items) and low (0?3 items) compliance groups. The primary and secondary outcomes were defined as 30-day survival and the development of endophthalmitis, with propensity score matching used to adjust for potential confounders.
Results. Among 230 patients, 160 (69.5%) were classified into the high compliance group, which exhibited significantly lower 30-day mortality than the low compliance group (8.8% vs 57.1%, P < .01). Even after matching, the high compliance group remained independently associated with improved survival (hazard ratio [HR]: 0.15; 95% confidence interval [CI]: .08?.30). C. albicans (HR: 1.95; 95% CI: 1.01?3.52) and central line-associated bloodstream infection (HR: 2.63; 95% CI: 1.35?5.12) were associated with the fatal outcome. Endophthalmitis involved 23.6% of the patients, being associated with C. albicans (odds ratio [OR]: 8.18; 4.46?19.30) and central line-associated bloodstream infection (OR: 2.69; 1.08?6.70).
Conclusions. Strict compliance to the Candida Care Bundle significantly improves survival, underscoring its importance in candidemia management. 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=HiguchiToshie en-aut-sei=Higuchi en-aut-mei=Toshie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyoshiTomoko en-aut-sei=Miyoshi en-aut-mei=Tomoko 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=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AkamatsuYukinobu en-aut-sei=Akamatsu en-aut-mei=Yukinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=IwamotoYoshitaka en-aut-sei=Iwamoto en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaShuichi en-aut-sei=Tanaka en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujisatoShun en-aut-sei=Fujisato en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AkoSoichiro en-aut-sei=Ako en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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 General Internal Medicine, Okayama Red Cross Hospital kn-affil= affil-num=4 en-affil=Center for Medical Education and Internationalization, Kyoto University Graduate School of Medicine 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=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of General Medicine, Tottori Municipal Hospital kn-affil= affil-num=8 en-affil=Department of Pharmacy, Tsuyama Chuo Hospital kn-affil= affil-num=9 en-affil=Department of General Medicine, NHO Okayama Medical Center kn-affil= affil-num=10 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Pharmacy, Okayama Rousai Hospital 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 Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=candida bundle kn-keyword=candida bundle en-keyword=candidemia kn-keyword=candidemia en-keyword=endophthalmitis kn-keyword=endophthalmitis en-keyword=prognosis kn-keyword=prognosis en-keyword=propensity score matching kn-keyword=propensity score matching END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Racialized Contagion and Defensive Biopolitics in The Last of Us en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the opening moments of the video game The Last of Us Part I, players are introduced to an emerging pandemic via Austinfs Texas Herald newspaper. Below a headline warning of mass hospitalizations from a 'mysterious infection', players read of a recall of imported crops 'potentially tainted with mold': 'Initial lists distributed to vendors nationwide warned against crops imported from South America. However now the scope has extended to include Central America and Mexico'. This scene immediately suggests the racialization of the franchisefs Cordyceps brain infection (CBI), with the contagion germinating in the global South, invading the US via its southern border, and spreading fastest in the nationfs diverse urban centres. By highlighting tainted crops as the vector of dispersal in the US, however, rather than infected humans, the franchise resists making this a simple invasion-scare narrative and instead suggests that the spread of the infection is in part a result of the capitalist exploitation of cheap land and labour in the global South. Despite its inconsistent record on racial representation and the near-absence of discussion of race across the franchise, the structures reflecting the racialization of contagion and the perpetuation of racialized hierarchies through defensive biopolitics remain present. Drawing connections with the discourse around immigration and the southern border and contemporary pandemics and epidemics, this article makes the case for reading the franchise in terms of racialized contagion and defensive biopolitics, a reading that highlights how the games and their television adaptation reflect urgent contemporary issues around race in America. en-copyright= kn-copyright= en-aut-name=YeatesRobert en-aut-sei=Yeates en-aut-mei=Robert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Faculty of Humanities and Social Sciences, Okayama University kn-affil= en-keyword=the last of us kn-keyword=the last of us en-keyword=contagion kn-keyword=contagion en-keyword=pandemics kn-keyword=pandemics en-keyword=race kn-keyword=race en-keyword=immigration kn-keyword=immigration en-keyword=biopolitics kn-keyword=biopolitics END start-ver=1.4 cd-journal=joma no-vol=49 cd-vols= no-issue=1 article-no= start-page=66 end-page=73 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exploratory Analysis for Development Predictive Models of Immune Checkpoint Inhibitor-Induced Myocarditis Using a Nationwide Claims Database en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immune checkpoint inhibitors (ICIs), essential in cancer therapy, can cause severe immune-related adverse events (irAEs), including myocarditis with a high fatality rate. Currently, the pathogenesis, biomarkers, and risk factors of ICI-induced myocarditis (ICIM) are not fully understood. This exploratory study aimed to develop machine learning-based models to predict the onset of ICIM within 3 months of starting ICI therapy, using a large health insurance database. The models were constructed using the Light Gradient Boosting Machine (LightGBM) and Random Forest algorithms, incorporating clinical variables such as comorbidities and prior medication classifications. In this study, a strategy combining undersampling and bagging was used to minimize the impact of highly imbalanced datasets. The Random Forest model demonstrated superior performance compared with the LightGBM model, and the SHapley Additive exPlanations (SHAP) analysis for the Random Forest model revealed that the concurrent use of ICIs was the most important variable for predictions. Although predictive performance remains limited (AUROC ? 0.63), this exploratory framework demonstrates the feasibility of developing data-driven risk prediction models for ICIM. Future studies with expanded datasets and integration of laboratory parameters are warranted to improve predictive accuracy and potential clinical applicability. en-copyright= kn-copyright= en-aut-name=YamamotoReina en-aut-sei=Yamamoto en-aut-mei=Reina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=NakagomiKoki en-aut-sei=Nakagomi en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UchiyamaMiyu en-aut-sei=Uchiyama en-aut-mei=Miyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MichiharaAyana en-aut-sei=Michihara en-aut-mei=Ayana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OzakiAya F. en-aut-sei=Ozaki en-aut-mei=Aya F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PatelPranav M. en-aut-sei=Patel en-aut-mei=Pranav M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TaniokaMaki en-aut-sei=Tanioka en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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 Pharmacy, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Pharmacy Practice, School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= affil-num=7 en-affil=Division of Cardiology, School of Medicine, University of California kn-affil= affil-num=8 en-affil=Medical AI Project, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=machine learning kn-keyword=machine learning en-keyword=immune checkpoint inhibitor kn-keyword=immune checkpoint inhibitor en-keyword=myocarditis kn-keyword=myocarditis en-keyword=adverse event kn-keyword=adverse event 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=35 cd-vols= no-issue= article-no= start-page= 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=Addition of human platelet lysate to islet culture medium suppresses islet loss and improves transplantation outcomes en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NoguchiHirofumi en-aut-sei=Noguchi en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Miyagi-ShiohiraChika en-aut-sei=Miyagi-Shiohira en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitohIssei en-aut-sei=Saitoh en-aut-mei=Issei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus kn-affil= affil-num=2 en-affil=Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatric Dentistry, Asahi University School of Dentistry 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=20251231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficient resuscitation of early-stage viable but non-culturable cells of Vibrio cholerae using treatment with proteolytic enzymes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vibrio cholerae, the etiological agent of cholera, is ubiquitous in environmental brackish waters. Exposure to low water temperatures induces the bacterium to enter a viable but non-culturable (VBNC) state. In this study, a stepwise decrease in water temperature to 4C was found to delay the transition to the non-culturable state compared to an abrupt temperature drop, suggesting that V. cholerae cells partially adapt to low temperatures. V. cholerae VBNC cells maintained at 4C gradually lost their ability to revert to a culturable state. However, VBNC cells in the early stage of dormancy were efficiently resuscitated following treatment with proteolytic enzymes, including proteinase K. The abundance of culturable V. cholerae cells in brackish estuarine waters was quantified using the most probable number (MPN)?quantitative polymerase chain reaction (qPCR) method. Although culturable cells were undetectable in samples treated with bovine serum albumin, they were estimated at 93 and 1,500 MPN/mL in two water samples collected on different days and pre-incubated with proteinase K. Similarly, the abundance of Vibrio species increased markedly following treatment with this enzyme. Additionally, cells of Vibrio species were enumerated by the plating method using CHROMagar Vibrio plates. Consistent with the results of the MPN?qPCR method, treatment with proteinase K resulted in over a 100-fold increase in colony formation. Collectively, these findings suggest that treatment with proteinase K is effective for resuscitating and quantifying V. cholerae VBNC cells in environmental water samples. en-copyright= kn-copyright= 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=1 ORCID= en-aut-name=OgasawaraMona en-aut-sei=Ogasawara en-aut-mei=Mona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NiwakiShiho en-aut-sei=Niwaki en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SugiharaRena en-aut-sei=Sugihara en-aut-mei=Rena 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=ImamuraDaisuke en-aut-sei=Imamura en-aut-mei=Daisuke 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=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Research Institute of Nursing Care for People and Community, University of Hyogo kn-affil= affil-num=6 en-affil=Research Center for Intestinal Health Science, Okayama University kn-affil= en-keyword=Vibrio cholerae kn-keyword=Vibrio cholerae en-keyword=viable but non-culturable kn-keyword=viable but non-culturable en-keyword=VBNC kn-keyword=VBNC en-keyword=protease kn-keyword=protease en-keyword=proteolytic enzyme kn-keyword=proteolytic enzyme 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=18 cd-vols= no-issue=1 article-no= start-page=e70066 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=A Procedural Transhiatal Approach for the Thoracic Para]Aortic Lymph Node: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=The thoracic posterior para-aortic lymph node (TPAN) is classified as an extra-regional lymph node in esophageal cancer, with metastasis indicating poor prognosis. However, some cases with suspected TPAN metastasis may benefit from esophagectomy with lymph node dissection, including TPAN. This report presents the case of a 58-year-old man with upper thoracic esophageal squamous cell carcinoma and suspected simultaneous TPAN metastasis who underwent neoadjuvant chemotherapy followed by thoracoscopic subtotal esophagectomy and procedural transhiatal TPAN dissection. This transhiatal approach provided direct access to the lymph node without additional thoracic incisions, ensuring safe resection in coordination with the assistant and following anatomical landmarks systematically. Pathological examination showed a false-positive TPAN finding, though the patient later developed distant recurrence. Compared with conventional approaches, this transhiatal technique allows for procedural and reproducible lymphadenectomy while minimizing respiratory burden. This case highlights the feasibility of a transhiatal approach for TPAN dissection. en-copyright= kn-copyright= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi 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=TakedaYasushige en-aut-sei=Takeda en-aut-mei=Yasushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 ORCID= en-aut-name=MaedaNaoaki en-aut-sei=Maeda en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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= en-keyword=112aoP kn-keyword=112aoP en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=thoracic posterior para-aortic lymph node kn-keyword=thoracic posterior para-aortic lymph node END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=2 article-no= start-page=129 end-page=130 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exposure-induced mediator?outcome confounders in causal mediation: implications and visualisation en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShinozakiTomohiro en-aut-sei=Shinozaki en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoEiji en-aut-sei=Yamamoto en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Interfaculty Initiative in Information Studies, the University of Tokyo kn-affil= affil-num=3 en-affil=Okayama University of Science kn-affil= END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=4 article-no= start-page=74 end-page= 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= kn-title=An Integrated QGIS-Based Evacuation Route Optimization Approach for Disaster Preparedness Against Urban Flood in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Urban inland flooding has become a serious problem in many cities because heavy rain often exceeds the capacity of drainage systems. In Japan, GIS-based evacuation maps are commonly used to support disaster preparedness, but they still have several limitations. In particular, they do not avoid flooded road segments and cannot generate multiple evacuation options at the same time. This study proposes an improved evacuation route method using the free and open-source software QGIS. The method combines flood-depth data with road network processing to remove roads where the predicted water depth is higher than 0.5 m. It also provides several evacuation paths to different shelters at the same time. A case study in Kurashiki City, Okayama Prefecture, demonstrates that about 1.37% of the road network becomes unusable during an inland-flood scenario. Several existing evacuation routes also pass through hazardous areas, but the QGIS-based method avoids these areas in most cases. Since the workflow uses only built-in QGIS functions and does not require programming or plug-ins, it is easy to reproduce and apply in other regions. This study offers a practical and low-cost method to support inland-flood evacuation planning for local governments. en-copyright= kn-copyright= en-aut-name=PanWenliang en-aut-sei=Pan en-aut-mei=Wenliang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PanShijun en-aut-sei=Pan en-aut-mei=Shijun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanetoJunko en-aut-sei=Kaneto en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaKeisuke en-aut-sei=Yoshida en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiyamaSatoshi en-aut-sei=Nishiyama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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= en-keyword=evacuation route kn-keyword=evacuation route en-keyword=hazard mapping kn-keyword=hazard mapping en-keyword=inland flood kn-keyword=inland flood en-keyword=land use analysis kn-keyword=land use analysis en-keyword=QGIS kn-keyword=QGIS END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=6 article-no= start-page=660 end-page=671 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250914 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Electronic Structure of the S1 State Manganese Cluster in Photosystem II Investigated Using Q-Band Selective Hole-Burning en-subtitle= kn-subtitle= en-abstract= kn-abstract=The electronic structure of the S1 state of photosystem II (PSII) was investigated using selective hole burning of Q-band pulsed electron paramagnetic resonance. The free induction decay and spin?echo signals of the tyrosine radical YD? in the plant PSII oscillated because of the magnetic dipole?dipole interaction with the S1 state Mn cluster. The initial period was 410 ns (2.44 MHz) and was assigned to the S = 1 spin state. Based on the oscillation analysis, both Mn1 and Mn4 and both Mn2 and Mn3 were assigned as Mn(III) and Mn(IV), respectively, which is consistent with the quantum chemical calculations. The 410 ns period was accounted for in the simplified model using the isotropic spin density distribution ratio [1.6:?1.1:?1.1:1.6] for Mn1?4 ions. This oscillation was identical with that observed in the presence of methanol. The oscillation decreased in PsbP/Q- and PsbO/P/Q-depleted PSII. In Thermosynechococcus vulcanus, two periods, 390 ns (2.56 MHz) and 630 ns (1.59 MHz), were detected, indicating that the cyanobacterial S1 state includes two isomers, S = 1 and S ? 2 spins. The S ? 2 spin was not detected in PsbO/U/V-depleted PSII without polyethylene glycol. The S ? 2 state was consistent with the reported quantum chemical calculation using S = 3. A simplified model accounted for the S = 1 state as the spin density distribution [1.8:?1.3:?1.3:1.8] and for the S ? 2 state as the isotropic spin density distribution [?0.5:0.5:0.5:0.5] for Mn1?4 ions. In combination with quantum chemical calculations, the most probable protonated structure is W1 = H2O, W2 = H2O, O4 = O2?, and O5 = O2? for the S1 state. These results demonstrate that the selective hole burning method is a powerful tool to complement X-ray studies to determine the valence and protonation structure of manganese clusters, not only in the S1 state but also in higher S-states and general metal clusters, which would provide important insights into the water oxidation mechanism. en-copyright= kn-copyright= en-aut-name=KosakiShinya en-aut-sei=Kosaki en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraNaohiko en-aut-sei=Nakamura en-aut-mei=Naohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=MinoHiroyuki en-aut-sei=Mino en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Physics, Graduate School of Science, Nagoya University kn-affil= affil-num=2 en-affil=Department of Physics, Graduate School of Science, Nagoya University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Department of Physics, Graduate School of Science, Nagoya University kn-affil= en-keyword=Photosystem II kn-keyword=Photosystem II en-keyword=Oxygen evolution kn-keyword=Oxygen evolution en-keyword=S1 state kn-keyword=S1 state en-keyword=Mn cluster kn-keyword=Mn cluster en-keyword=EPR kn-keyword=EPR en-keyword=Selective hole-burning kn-keyword=Selective hole-burning 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 gattenuated LFSh 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 gLFSh 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=13 cd-vols= no-issue=4 article-no= start-page=1041 end-page=1054 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250904 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Asian Subgroup Analysis of Patients in the Phase 2 DeLLphi-301 Study of Tarlatamab for Previously Treated Small Cell Lung Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Tarlatamab is a bispecific T-cell engager (BiTE?) immunotherapy that binds delta-like ligand 3 on the surface of small cell lung cancer (SCLC) cells and CD3 on T cells, facilitating T cell-mediated cancer cell lysis. In the primary analysis of the phase 2 DeLLphi-301 study (NCT05060016), tarlatamab showed a favourable benefit-to-risk profile with durable objective responses and promising survival outcomes in patients with previously treated SCLC. Here, phase 2 data for the Asia region subgroup are presented.
Methods: Patients with previously treated, advanced SCLC received 10 mg tarlatamab every 2 weeks. The primary endpoint was objective response rate (ORR) by blinded independent central review (RECIST version 1.1). Key secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety. The present analysis includes patients enrolled at sites in Asia.
Results: A total of 43 patients were enrolled at sites in Asia. ORR was 46.3% (95% confidence interval [CI], 30.7?62.6) and median DOR was 7.2 months (95% CI 3.9 to not estimable). The median follow-up was 16.6 months for PFS and 21.2 months for OS. Median PFS was 5.4 months (95% CI 3.0?8.1) and median OS was 19.0 months (95% CI 11.4 to not estimable). The most common treatment-emergent adverse event (AE) was cytokine release syndrome (48.8%), and all such events were grade 1 or 2. There were no discontinuations due to treatment-related AEs.
Conclusions: Tarlatamab demonstrated durable responses and promising survival outcomes with a manageable safety profile in this post hoc analysis of patients from Asia with previously treated SCLC.
Trial Registration: ClinicalTrials.gov, NCT05060016. 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=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=IzumiHiroki en-aut-sei=Izumi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=HanJi-Youn en-aut-sei=Han en-aut-mei=Ji-Youn kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ChiangChi-Lu en-aut-sei=Chiang en-aut-mei=Chi-Lu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=HamidiAli en-aut-sei=Hamidi en-aut-mei=Ali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=XuKrista Lin en-aut-sei=Xu en-aut-mei=Krista Lin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AkamatsuHiraoki en-aut-sei=Akamatsu en-aut-mei=Hiraoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Hematology-Oncology Department, Samsung Medical Center (SMC), Sungkyunkwan University School of Medicine kn-affil= affil-num=2 en-affil=Medical Oncology Department-501, ABMRC, Yonsei University kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Thoracic Oncology, National Cancer Center Hospital East kn-affil= affil-num=5 en-affil=Hematology/Oncology, Seoul National University Bundang Hospital kn-affil= affil-num=6 en-affil=Center for Lung Cancer, National Cancer Center-Graduate School of Cancer Science and Policy kn-affil= affil-num=7 en-affil=Department of Chest Medicine, Taipei Veterans General Hospital kn-affil= affil-num=8 en-affil=Amgen Inc. kn-affil= affil-num=9 en-affil=Amgen Inc. kn-affil= affil-num=10 en-affil=Amgen Inc. kn-affil= affil-num=11 en-affil=Amgen Asia Pacific Pte. Ltd. kn-affil= affil-num=12 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= en-keyword=Small cell lung cancer (SCLC) kn-keyword=Small cell lung cancer (SCLC) en-keyword=Tarlatamab kn-keyword=Tarlatamab en-keyword=DLL3 kn-keyword=DLL3 en-keyword=Bispecific T-cell engager kn-keyword=Bispecific T-cell engager en-keyword=Asian patients kn-keyword=Asian patients END start-ver=1.4 cd-journal=joma no-vol=193 cd-vols= no-issue= article-no= start-page=118724 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=Deciphering the structural impact of norepinephrine analog radiopharmaceuticals on organic cation transporter affinity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: Previous studies have investigated the kinetics and affinities of norepinephrine transporter (NET)-targeting radiotracers, including [123I]MIBG, but the role of organic cation transporters (OCTs) remains unclear. This study aimed to evaluate how the structural design of selective NET-targeting tracers affects OCT-mediated non-specific uptake, identifying factors influencing both NET and OCT affinity.
Methods: Cellular uptake assays were conducted using SK-N-SH cells expressing human NET, and human OCT1-, OCT2-, and OCT3-expressing cells with [3H]norepinephrine, [3H]MPP+, and [131I]MIBG. Competitive uptake assays used non-radioactive reference compounds for several NET-targeting radiopharmaceuticals (MIBG, HED, EPI, PHEN, LMI1195, and PHPG), along with a new PET radiotracer [18F]AF78, and its two analogs with meta-iodide [18F]AF78(I) or hydroxyl group [18F]AF78(OH). Dynamic PET imaging in non-human primates assessed the in vivo uptake of [18F]AF78 after NET inhibition with desipramine.
Results: Monoamine-based tracers (EPI, PHEN, HED) exhibited high NET selectivity with minimal OCTs interaction, while guanidine-containing tracers (e.g., MIBG, LMI1195) displayed substantial OCTs affinity. Lower lipophilicity in guanidine-containing compounds, influenced by substitutions on the benzene ring (e.g., PHPG, AF78), correlated with weaker OCT interactions. PET imaging confirmed that cardiac uptake of [18F]AF78 is sensitive to desipramine pretreatment (***P? Conclusion: This study highlights the critical influence of the compoundsf chemical structure on NET and OCT affinities. Structural modifications that reduce OCT-mediated uptake while maintaining high NET affinity could improve the specificity and theranostic potential of NET-targeting ligands. These findings provide insights for designing next-generation radiotracers with enhanced selectivity and clinical utility. en-copyright= kn-copyright= en-aut-name=M?hligSaskia en-aut-sei=M?hlig en-aut-mei=Saskia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChenXinyu en-aut-sei=Chen en-aut-mei=Xinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TutovAnna en-aut-sei=Tutov en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NoseNaoko en-aut-sei=Nose en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LapaConstantin en-aut-sei=Lapa en-aut-mei=Constantin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WernerRudolf A. en-aut-sei=Werner en-aut-mei=Rudolf A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DeckerMichael en-aut-sei=Decker en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiguchiTakahiro en-aut-sei=Higuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital W?rzburg kn-affil= affil-num=2 en-affil=Nuclear Medicine, Faculty of Medicine, University of Augsburg kn-affil= affil-num=3 en-affil=Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of W?rzburg kn-affil= affil-num=4 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Nuclear Medicine, Faculty of Medicine, University of Augsburg kn-affil= affil-num=6 en-affil=Department of Nuclear Medicine, LMU Hospital, Ludwig-Maximilians-University of Munich kn-affil= affil-num=7 en-affil=Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of W?rzburg kn-affil= affil-num=8 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Norepinephrine transporter kn-keyword=Norepinephrine transporter en-keyword=Organic cation transporter kn-keyword=Organic cation transporter en-keyword=Neuroendocrine tumor kn-keyword=Neuroendocrine tumor en-keyword=Competitive cell uptake kn-keyword=Competitive cell uptake en-keyword=PET radiotracer kn-keyword=PET radiotracer 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=Daytime Bladder Control Status in Toddlerhood Is Associated With Subsequent Bedwetting in Preschool Years: A Nationwide Cohort Study of Over 30?000 Japanese Children en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Nocturnal enuresis is common in early childhood. While daytime bladder control typically precedes nighttime continence, the temporal relationship between early daytime bladder control and subsequent bedwetting remains unclear. We investigated whether daytime bladder control status at age 2.5?years?as indicated by diaper use?is associated with bedwetting at age 4.5?years in a Japanese nationwide cohort.
Methods: We analyzed data from the Japanese Longitudinal Survey of Newborns in the 21st Century (2010 cohort). Daytime bladder control was assessed at age 2.5?years through caregiver-reported diaper use, and bedwetting frequency at age 4.5?years through parental questionnaires. Modified Poisson regression estimated risk ratios (RRs), adjusting for birth-related factors, socioeconomic status, daycare attendance, and developmental milestones.
Results: Among 32?168 children, 26?651 (82.8%) still used diapers at 2.5?years. Bedwetting prevalence at 4.5?years was 42.2%: 34.5% in children who achieved daytime bladder control at 2.5?years versus 43.9% in those still using diapers. After multivariable adjustment, incomplete daytime bladder control at 2.5?years was associated with higher bedwetting risk (adjusted RR 1.25; 95% CI, 1.20?1.31). Multinomial regression revealed dose?response relationships: odds ratios 1.41 (95% CI, 1.30?1.52) for gsometimesh and 1.58 (95% CI, 1.42?1.77) for goftenh bedwetting.
Conclusions: Daytime bladder control status at 2.5?years was associated with a 25% increased bedwetting risk at 4.5?years. This association likely reflects individual differences in bladder control maturation rather than causal effects. While daytime bladder control may serve as a developmental marker, its validity as an intervention target remains unestablished. en-copyright= kn-copyright= en-aut-name=MoriwakeTakatoshi en-aut-sei=Moriwake en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UraguchiKensuke en-aut-sei=Uraguchi en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiTomoko en-aut-sei=Kobayashi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshinagaKasumi en-aut-sei=Yoshinaga en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamanoiTomoaki en-aut-sei=Yamanoi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakaoSoshi en-aut-sei=Takao en-aut-mei=Soshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 ORCID= affil-num=1 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Urology Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama Japan kn-affil= affil-num=10 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=18 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=bedwetting kn-keyword=bedwetting en-keyword=cohort study kn-keyword=cohort study en-keyword=daytime bladder control kn-keyword=daytime bladder control en-keyword=nocturnal enuresis kn-keyword=nocturnal enuresis END start-ver=1.4 cd-journal=joma no-vol=113 cd-vols= no-issue=4 article-no= start-page=117030 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=Time to positivity for differentiating blood culture contamination: A 20-hour cutoff for major contaminants en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Blood culture remains the gold standard for diagnosing bacteremia; however, contamination inevitably occurs in 2-3% of cases, requiring differentiation between true bacteremia and contamination. Although time to positivity (TTP) aids in this clinical decision, with detection after 24 hours generally indicating contamination, technological advances in blood culture systems may have shortened this threshold interval.
Methods: This study retrospectively analyzed blood culture data in our hospital from April 2023 to January 2025 to determine the optimal TTP cutoff. Patients with positive blood cultures for major contaminating bacteria were included. Cases were classified as true bacteremia or contamination based on a comprehensive chart review conducted by the antimicrobial stewardship audit, and TTP was compared between the groups. Sensitivity, specificity, and Youden index at various TTP cutoffs were utilized to determine the optimal threshold using the receiver operating characteristic curve analysis.
Results: Seventy-one patients were enrolled, with 34 cases classified as true bacteremia and 37 as contamination. Identified bacteria included coagulase-negative staphylococci (70.4%), viridans group streptococci (18.3%), and others (11.3%). The median TTP was significantly shorter in the true bacteremia group compared with the contamination group (18.6 vs.25.8 hours, p < 0.001). In the contamination group, 43.2% of the cases demonstrated positive growth within 24 hours. Based on sensitivity, specificity, and Youden index, the optimal threshold was estimated to be 20 hours. A subgroup analysis of the CNS-only cohort yielded concordant results.
Conclusion: This study suggests that a 20-hour TTP threshold could help effectively differentiate true bacteremia from contamination in current clinical settings. en-copyright= kn-copyright= en-aut-name=ManabeYohei en-aut-sei=Manabe en-aut-mei=Yohei 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=NakamotoKenta en-aut-sei=Nakamoto en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=AkazawaHidemasa en-aut-sei=Akazawa en-aut-mei=Hidemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujitaYasushi en-aut-sei=Fujita en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KiguchiTakashi en-aut-sei=Kiguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Department of Pharmacy, 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 Infectious Diseases, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Nursing, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Nursing, Okayama University Hospital kn-affil= affil-num=9 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= en-keyword=Bacteremia kn-keyword=Bacteremia en-keyword=Blood stream infection kn-keyword=Blood stream infection en-keyword=Contamination kn-keyword=Contamination en-keyword=Incubation time kn-keyword=Incubation time en-keyword=Time to positivity kn-keyword=Time to positivity END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=12 article-no= start-page=e71586 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=Experience and Insight Into Genetic Diagnosis of Infective Aortic Aneurysm en-subtitle= kn-subtitle= en-abstract= kn-abstract=Culture-negative infected aneurysms possibly occur in various clinical situations, including prior antibiotic exposure. Accurate microbial identification is crucial for an optimal antimicrobial strategy. 16S ribosomal RNA gene sequence analysis would provide a useful tool for precise bacterial identification. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke 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=FujimoriTakumi en-aut-sei=Fujimori en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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 General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=4 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= en-keyword=16S rRNA kn-keyword=16S rRNA en-keyword=culture-negative kn-keyword=culture-negative en-keyword=Enterobacter hormaechei kn-keyword=Enterobacter hormaechei en-keyword=infected aneurysm kn-keyword=infected aneurysm END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=12 article-no= start-page=e71698 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=Mycobacterium intracellulare-Induced Flexor Tenosynovitisof the Forearm en-subtitle= kn-subtitle= en-abstract= kn-abstract=We herein document a clinically challenging case of Mycobacterium intracellulare tenosynovitis in an immunocompromised patient with rheumatoid arthritis. Diagnosing nontuberculous mycobacterial tenosynovitis is often challenging because it often mimics rheumatoid arthritis flares. Combination antimycobacterial therapy combined with surgical intervention is essential for the treatment of this refractory condition. en-copyright= kn-copyright= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu 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= 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= en-keyword=Mycobacterium avium complex kn-keyword=Mycobacterium avium complex en-keyword=Mycobacterium intracellulare kn-keyword=Mycobacterium intracellulare en-keyword=soft tissue infection kn-keyword=soft tissue infection en-keyword=tenosynovitis kn-keyword=tenosynovitis END start-ver=1.4 cd-journal=joma no-vol=113 cd-vols= no-issue=5 article-no= start-page=942 end-page=943 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Scapular Tuberculosis en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NakamotoKenta en-aut-sei=Nakamoto en-aut-mei=Kenta 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=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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= en-keyword=Mycobacterium tuberculosis kn-keyword=Mycobacterium tuberculosis en-keyword=Osteo-articular tuberculosis kn-keyword=Osteo-articular tuberculosis en-keyword=cold abscess kn-keyword=cold abscess END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=10 article-no= start-page=e71249 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=Recurrent Septic Shock in Immunosuppressed Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cytomegalovirus gastroenteritis presents with diarrhea and abdominal pain in immunosuppressed patients, and histopathological examination is essential by endoscopy. This case illustrates that cytomegalovirus enteritis may develop insidiously and possibly invoke shock in immunocompromised patients, warranting its inclusion in the differential diagnosis of recurrent septic shock. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujitaKoji en-aut-sei=Fujita en-aut-mei=Koji 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= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Medicine and Infectious Diseases, Tsuyama Chuo Hospital kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=bacteremia kn-keyword=bacteremia en-keyword=compromised host kn-keyword=compromised host en-keyword=cytomegalovirus kn-keyword=cytomegalovirus en-keyword=septic shock kn-keyword=septic shock 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 ?g/mL), ceftriaxone (MIC, 16 ?g/mL), meropenem (MIC, 1 ?g/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=190 cd-vols= no-issue=6 article-no= start-page=90 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognostic Value of Serum (13)--D-Glucan Levels in Patients with Candidemia Stratified by Compliance with Candida Bundle: A Multicenter Retrospective Cohort Study (2016?2023) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Candidemia is a severe systemic infection with a high mortality risk. While -D-glucan (BDG) serves as a diagnostic biomarker, its prognostic value in candidemia, particularly in association with Candida bundle compliance, remains unclear.
Methods In this retrospective multicenter cohort study, we evaluated 96 patients with candidemia across nine Japanese hospitals between 2016 and 2023. Candida bundle compliance was assessed using five key components: central venous catheter removal within 24 h of diagnosis, appropriate initial antifungal therapy, ophthalmologic examination, follow-up blood cultures until clearance, and antifungal therapy for at least two weeks post-clearance. Analyses stratified patients by serum BDG status (positive/negative) and compliance with the Candida bundle (high: 4?5 points; low: 0?3 points). The primary outcome was 30-day mortality, and the secondary outcome was defined as endophthalmitis incidence.
Results Of 96 eligible patients with candidemia, 70 (72.9%) were BDG-positive and 26 (27.1%) were BDG-negative. The overall 30-day mortality was 17.7%. Among BDG-positive patients, 15 (21.4%) died, while 2 (7.7%) died in BDG-negative cohorts (p?=?0.09). Serum BDG positivity demonstrated a statistically significant association with decreased survival rates in the low bundle adherence group (p?=?0.02), whereas this correlation was not observed among patients in the high-compliance cohort (p?=?0.66). Endophthalmitis occurred in 25.0% of patients, without significant correlation to serum BDG status. C. albicans was associated with a significantly higher incidence of endophthalmitis compared with non-albicans species (45.7% vs. 8.9%).
Conclusions Serum BDG positivity potentially correlates with worse survival in candidemia, particularly in patients with low bundle compliance. This emphasizes the importance of adherence to standardized Candida management protocols for optimizing patient outcomes. 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=HiguchiToshie en-aut-sei=Higuchi en-aut-mei=Toshie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyoshiTomoko en-aut-sei=Miyoshi en-aut-mei=Tomoko 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=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AkamatsuYukinobu en-aut-sei=Akamatsu en-aut-mei=Yukinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=IwamotoYoshitaka en-aut-sei=Iwamoto en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaShuichi en-aut-sei=Tanaka en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujisatoShun en-aut-sei=Fujisato en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AkoSoichiro en-aut-sei=Ako en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=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 Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of General Internal Medicine, Okayama Red Cross Hospital kn-affil= affil-num=4 en-affil=Center for Medical Education and Internationalization, Kyoto University Graduate School of Medicine 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=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of General Medicine, Tottori Municipal Hospital kn-affil= affil-num=8 en-affil=Department of Pharmacy, Tsuyama Chuo Hospital kn-affil= affil-num=9 en-affil=Department of General Medicine, NHO Okayama Medical Center kn-affil= affil-num=10 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Pharmacy, Okayama Rousai Hospital 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 Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Candidemia kn-keyword=Candidemia en-keyword=Prognosis kn-keyword=Prognosis en-keyword=-D-glucan kn-keyword=-D-glucan en-keyword=Candida bundle kn-keyword=Candida bundle en-keyword=Endophthalmitis kn-keyword=Endophthalmitis END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=100718 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=Should Japanese athletes undergo booster vaccination for pertussis? en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pertussis, a highly contagious respiratory infection caused by Bordetella pertussis, has demonstrated a global resurgence in the post?COVID-19 era, with the emergence of macrolide-resistant strains. In Japan, the routine immunization schedule for pertussis remains limited compared with international standards, leaving young populations under-immunized and at elevated risk of infection. Despite international recommendations for booster vaccinations during adolescence, Japan currently provides only a four-dose primary series during infancy, without subsequent boosters. This immunization gap possibly increases the vulnerability of Japanese athletes to pertussis. Persistent cough can significantly impair athletic performance for weeks to months, posing substantial challenges to professional sports teams. To protect athletesf health and performance capacity and prevent team-wide outbreaks, it is imperative to consider pertussis booster immunizations in Japan, especially for elite athletes. However, DTaP (diphtheria, tetanus, and acellular pertussis) (TRIBIK?) is the only available vaccine in Japan, which contains higher antigen concentrations than the internationally used Tdap (tetanus, diphtheria, pertussis) vaccines (ADACEL? and BOOSTRIX?): the antigen contents of pertussis toxin, filamentous hemagglutinin, and diphtheria toxin in TRIBIK?, ADACEL?, and BOOSTRIX? are 23.5 ?g/23.5 ?g/?15 ?g, 2.5 ?g/5 ?g/2 ?g, and 8 ?g/8 ?g/2.5 ?g, respectively. These differences result in more severe local adverse effects in vaccinees and would complicate booster strategies in Japan. Aligning Japanfs immunization policies with international practices represents a critical step toward ensuring individual health and public safety in increasingly globalized sports environments. en-copyright= kn-copyright= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Bordetella pertussis kn-keyword=Bordetella pertussis en-keyword=Vaccination kn-keyword=Vaccination en-keyword=Immunization kn-keyword=Immunization END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=6 article-no= start-page=e70230 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=Corynebacterium striatum-Associated Pyogenic Osteomyelitis With Direct Extension From Postoperative Empyema en-subtitle= kn-subtitle= en-abstract= kn-abstract=Corynebacterium striatum can cause postoperative empyema. C. striatum-associated empyema may be associated with osteomyelitis. Rifampicin is a viable therapeutic option for C. striatum infection. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke 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=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital 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 Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Corynebacterium striatum kn-keyword=Corynebacterium striatum en-keyword=empyema kn-keyword=empyema en-keyword=osteomyelitis kn-keyword=osteomyelitis en-keyword=rifampicin kn-keyword=rifampicin END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=1 article-no= start-page=100026 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=Severe Intracranial Infection en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujimoriTakumi en-aut-sei=Fujimori en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=2 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=3 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=bloodstream infection kn-keyword=bloodstream infection en-keyword=brain abscess kn-keyword=brain abscess en-keyword=mixed infection kn-keyword=mixed infection END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=9 article-no= start-page=e0329451 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250904 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of COVID-19 on the awareness and interest in infectious disease specialization among Japanese medical students en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
The SARS-CoV-2 pandemic has highlighted the critical deficiency of infectious disease (ID) specialists, a subspecialty that remains underrepresented among Japanese medical students.
Methods
This nationwide cross-sectional survey was administered between April and August 2024 via an online questionnaire distributed to medical students throughout Japan. The survey assessed awareness of and interest in ID specialization, categorizing students by academic year: lower (first- and second-year students), middle (third- and fourth-year students), and upper grades (fifth- and sixth-year students).
Results
Of 502 respondents, data for 492 medical students were eligible, of whom 69.7% demonstrated awareness of ID specialists, with recognition rates increasing proportionally with academic progression. Regarding career aspirations, 9.8% of respondents expressed interest in pursuing ID specialization, with the highest proportion observed among upper-grade students (19.4%). Male students (14.8%) expressed greater interest in ID specialization than female students (5.2%). The pandemic positively influenced 5.5% of students to consider ID specialization as a future career, whereas only 0.6% reported a negative impact.
Conclusions
These findings underscore the necessity of enhanced educational initiatives to promote ID specialization among medical students, addressing current shortages and future infectious disease preparedness. en-copyright= kn-copyright= en-aut-name=KamadaNaruto en-aut-sei=Kamada en-aut-mei=Naruto 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=KutsunaSatoshi en-aut-sei=Kutsuna en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Faculty of Medicine, Wakayama Medical University kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Infection Control and Prevention, Graduate School of Medicine, Osaka University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=7 article-no= start-page=oyaf201 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=Pharmacovigilance study for the identification of mogamulizumab-induced immune-related adverse events using a real-world database en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Mogamulizumab is a humanized anti-CCR4 monoclonal antibody used for relapsed/refractory adult T-cell leukemia, cutaneous T-cell lymphoma, and/or S?zary syndrome. Reports of immune-related adverse events (irAEs) in these patients are increasing, and the association between irAEs and mogamulizumab remains to be elucidated. This study aimed to evaluate the association between mogamulizumab and immune-related adverse events (irAEs), as well as to characterize the irAEs associated with mogamulizumab using data from a large-scale spontaneous reporting system.
Methods: We performed an exploratory hypothesis-generating analysis of patients from 1967 to September 2023 using VigiBase, a World Health Organization spontaneous adverse event reporting system database. We performed a disproportionality analysis and determined the reporting odds ratios and information components between the drugs of interest and each irAE.
Results: Mogamulizumab was associated with some irAEs, including myocarditis, severe cutaneous adverse reactions, hepatitis, and myositis. Mogamulizumab exhibited significantly higher reporting rates of these 4 irAEs compared to the anticancer agents other than mogamulizumab. Conversely, the reporting rate of other irAEs, including endocrine autoimmune diseases induced by immune checkpoint inhibitors, was not significant in patients who received mogamulizumab.
Conclusions: Mogamulizumab is associated with irAEs, including myocarditis, severe cutaneous adverse reactions, hepatitis, and myositis. en-copyright= kn-copyright= en-aut-name=MiyataKoji en-aut-sei=Miyata en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Izawa-IshizawaYuki en-aut-sei=Izawa-Ishizawa en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NiimuraTakahiro en-aut-sei=Niimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshiokaToshihiko en-aut-sei=Yoshioka en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HyodoMizusa en-aut-sei=Hyodo en-aut-mei=Mizusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItokazuShuto en-aut-sei=Itokazu en-aut-mei=Shuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyataTatsumi en-aut-sei=Miyata en-aut-mei=Tatsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AizawaFuka en-aut-sei=Aizawa en-aut-mei=Fuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YagiKenta en-aut-sei=Yagi en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawadaKei en-aut-sei=Kawada en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 ORCID= en-aut-name=GodaMitsuhiro en-aut-sei=Goda en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IshizawaKeisuke en-aut-sei=Ishizawa en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=2 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=3 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=4 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=5 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=6 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=7 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=8 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=9 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=10 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=11 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=14 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= en-keyword=irAEs kn-keyword=irAEs en-keyword=mogamulizumab kn-keyword=mogamulizumab en-keyword=VigiBase kn-keyword=VigiBase en-keyword=disproportionality analysis kn-keyword=disproportionality analysis en-keyword=s?zary syndrome kn-keyword=s?zary syndrome END start-ver=1.4 cd-journal=joma no-vol=122 cd-vols= no-issue=5 article-no= start-page=733 end-page=743 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250715 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Intravenous umbilical cord-derived mesenchymal stromal cell therapy may improve overall survival in Japanese patients with idiopathic pneumonia syndrome after hematopoietic stem cell transplantation: a multicenter, single-arm, phase II trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Idiopathic pneumonia syndrome (IPS) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT) and has a poor prognosis. Although IPS is often treated with steroids, the disease can become resistant to or dependent on steroid treatment, and there is no effective cure for patients with refractory or steroid-dependent IPS. This multicenter, open-label, single-arm, phase II clinical trial investigated the efficacy and safety of HLC-001 (allogeneic umbilical cord-derived mesenchymal stromal cells) in patients with progressive steroid-dependent or refractory IPS after HSCT. Seven male patients (all male; mean age: 43.3 years) received HLC-001 and three completed the trial. The survival rate at day 56 (primary endpoint) was 71.4% (5/7 patients; 95% confidence interval: 29.0%?96.3%) and was sustained at day 100, suggesting that HLC-001 was more effective than previously reported treatment. Three of the five patients with ??100 days of follow-up died. Five patients experienced at least one adverse drug reaction, none of which were serious. These findings indicate that HLC-001 was potentially effective and generally well tolerated in Japanese patients with steroid-dependent or refractory IPS after HSCT. Given there is no effective cure for steroid-dependent or refractory IPS, HLC-001 may be a promising treatment option and further clinical evaluation is warranted.
Trial registration: Japan Registry of Clinical Trials identifier: jRCT2063220014. en-copyright= kn-copyright= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KakoShinichi en-aut-sei=Kako en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakaidaEmiko en-aut-sei=Sakaida en-aut-mei=Emiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= affil-num=1 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Center kn-affil= affil-num=4 en-affil=Department of Hematology, Chiba University Hospital kn-affil= affil-num=5 en-affil=Division of Hematology, Department of Medicine, Jichi Medical University kn-affil= en-keyword=Graft-versus-host disease kn-keyword=Graft-versus-host disease en-keyword=Hematopoietic stem cell transplantation kn-keyword=Hematopoietic stem cell transplantation en-keyword=Idiopathic pneumonia syndrome kn-keyword=Idiopathic pneumonia syndrome en-keyword=Overall survival kn-keyword=Overall survival en-keyword=Umbilical cord-derived mesenchymal stromal cells kn-keyword=Umbilical cord-derived mesenchymal stromal cells END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=45 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=Magnetic Detection of Cancer Cells Using Tumor-Homing Peptide-Modified Magnetic Nanoparticles en-subtitle= kn-subtitle= en-abstract= kn-abstract=Magnetic nanoparticles (MNPs) provide a platform for target detection because of their magnetic responsiveness to alternating magnetic fields (AMFs). We developed a detection method using MNPs modified with tumor-homing peptides (THPs), PL1 and PL3, which selectively bind to protein components enriched in malignant tissues. THP-MNPs were synthesized using maleimide-PEG-NHS linkers and characterized using transmission electron microscopy. Human glioblastoma cancer U87MG and normal tissue-derived HEK293 cells were incubated with THP-MNPs, and the magnetic signals were measured using a high-temperature superconducting quantum interference device (SQUID) magnetometer under an AMF (1.06 kHz). Dark-field microscopy confirmed the preferential binding of THP-MNPs to U87MG cells. In the absence of cells, THP-MNPs exhibited AMF-dependent signal enhancement, which correlated with particle size reduction due to THP release. This increase was completely suppressed in the presence of U87MG cells, indicating a strong THP-mediated interaction. PL3-MNPs exhibited superior discrimination between malignant and non-malignant cells. These results demonstrate that SQUID-based magnetic measurements using THP-MNPs enable rapid and label-free cancer cell detection. en-copyright= kn-copyright= en-aut-name=ZhouShengli en-aut-sei=Zhou en-aut-mei=Shengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FurutaniYuji en-aut-sei=Furutani en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamashitaKei en-aut-sei=Yamashita en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KakoSakuya en-aut-sei=Kako en-aut-mei=Sakuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeKazunori en-aut-sei=Watanabe en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KiwaToshihiko en-aut-sei=Kiwa en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= affil-num=1 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama 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 Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=magnetic nanoparticle kn-keyword=magnetic nanoparticle en-keyword=tumor-homing peptide kn-keyword=tumor-homing peptide en-keyword=superconducting quantum interference devices kn-keyword=superconducting quantum interference devices END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=5 article-no= start-page=e70094 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=Seaweed Extracts Improve Salinity Tolerance in Cereal Crops?A Meta]Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Seaweeds are considered an essential component of the blue economy. Because seaweed extracts are rich in bioactive compounds that enhance plant stress resilience, exploiting this resource could offer a sustainable solution for crop production. Salinity is a major abiotic challenge that significantly impacts crop yield and food security. Through meta-analysis, we explored whether the exogenous application of seaweed extracts improves the salt tolerance of cereal crops. All the studies chosen for this study utilized aqueous seaweed extracts as foliar sprays. A multi-level meta-analysis with a mixed effects model was performed to determine the effect size. This meta-analysis demonstrated that applying aqueous seaweed extracts enhanced the shoot and root biomass under normal and salinity stress conditions, suggesting that seaweed extract can help improve crop stress tolerance. The seaweeds studied belonged to three classes: Phaeophyceae, Rhodophyta, and Chlorophyta, with extracts from Chlorophyta and Phaeophyceae significantly enhancing biomass production under salinity conditions. Applying aqueous seaweed extracts effectively improved salinity tolerance at both 34.2?100?mM and 101?400?mM NaCl equivalent salinity stress. Moreover, exogenous foliar application of ??25% aqueous seaweed extracts was most effective for improving salinity tolerance in cereals. The impact of seaweed extracts on cereal crop yields has not been extensively reported; therefore, further studies should focus on this aspect. en-copyright= kn-copyright= en-aut-name=NuruzzamanMd. en-aut-sei=Nuruzzaman en-aut-mei=Md. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Tahjib]Ul]ArifMd. en-aut-sei=Tahjib]Ul]Arif en-aut-mei=Md. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HannanMd. Abdul en-aut-sei=Hannan en-aut-mei=Md. Abdul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MurataYoshiyuki en-aut-sei=Murata en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HossainM. Afzal en-aut-sei=Hossain en-aut-mei=M. Afzal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Plant Resources, College of Industrial Sciences, Kongju National University kn-affil= affil-num=2 en-affil=Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University kn-affil= affil-num=3 en-affil=Department of Biochemistry and Molecular Biology, Bangladesh Agricultural 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=Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University kn-affil= en-keyword=abiotic stress kn-keyword=abiotic stress en-keyword=crop tolerance kn-keyword=crop tolerance en-keyword=marine algae kn-keyword=marine algae en-keyword=plant growth kn-keyword=plant growth en-keyword=salt stress kn-keyword=salt stress en-keyword=sustainable agriculture kn-keyword=sustainable agriculture END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=6 article-no= start-page=1405 end-page=1416 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical significance on switching CDK4/6 inhibitors among 13,284 patients with metastatic breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent clinical trials have shown that switching to a combination therapy of a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) prolongs progression-free survival (PFS) compared with ET monotherapy. Reports indicate that abemaciclib provides benefits regardless of the PIK3CA mutation status; however, its clinical benefits remain insufficient. This study aimed to evaluate the clinical significance of switching CDK4/6i?+?ET in a large real-world cohort. Using a medical database, we identified 13,284 patients with hormone receptor?positive/human epidermal growth factor receptor 2?negative advanced breast cancer who received CDK4/6i?+?ET between 2008 and 2022. Patients were categorized into five groups based on their first- and second-line therapy patterns. We compared the median time to discontinuation (TTD) among the groups. In patients who switched from one CDK4/6i?+?ET to another CDK4/6i?+?ET, the second-line TTD and total TTD of first- and second-line therapies (n?=?542) were significantly longer than those in patients who switched from CDK4/6i?+?ET to ET monotherapy (n?=?490) (the second-line TTD: 11.2 vs. 4.9 months, p? 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. Lukefs International Hospital, St. Lukefs 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=14 cd-vols= no-issue= article-no= start-page=100511 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genetic variability in Neisseria meningitidis strains isolated in a Japanese hospital en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Neisseria meningitidis is a significant pathogen causing invasive meningococcal disease, posing clinical and public health concerns worldwide. This study aimed to investigate the genetic characteristics of N. meningitidis clinical isolates at Okayama University Hospital in Japan.
Methods: Between 2018 and 2023, five clinical strains were isolated, of which three were subjected to the antimicrobial susceptibility testing and whole genetic analysis using MiSeq platform (Illumina, San Diego, CA, USA).
Results: One non-groupable isolate, belonging to sequence types (STs)-11026 (ST-32 complex), exhibited non-susceptibility to penicillin G, with a five-mutation pattern (F504L, A510V, I515V, H541N, and I566V) in the penA amino acid sequence and additional mutations (XXXIV and N513Y) characteristic of a mosaic penA gene. The other two isolates, ST-1655 (ST-23 complex) with serogroup Y and ST-2057 with serogroup B, were susceptible to penicillin G, neither of which contained the five-mutation pattern. Levofloxacin resistance was observed in two isolates carrying the T91I mutation in the gyrA protein.
Conclusion: Our findings suggest the presence of antimicrobial-resistant N. meningitidis in Japan, underscoring the necessity for continuous local surveillance. Additional research is crucial for clarifying the ongoing spread of resistance mechanisms and for establishing effective countermeasures to reduce the clinical burden of invasive meningococcal disease. en-copyright= kn-copyright= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi 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=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=MatsushitaOsamu en-aut-sei=Matsushita en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health 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 Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Antimicrobial resistance kn-keyword=Antimicrobial resistance en-keyword=Invasive meningococcal disease kn-keyword=Invasive meningococcal disease en-keyword=Drug-resistant gene kn-keyword=Drug-resistant gene en-keyword=Genome sequence kn-keyword=Genome sequence END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=12 article-no= start-page=e00740-25 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genomic portrayal of emerging carbapenem-resistant El Tor variant Vibrio cholerae O1 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The escalating prevalence of carbapenem-resistant (CR) enteric pathogens elicits significant challenges to public health management and effective antimicrobial therapy. While carbapenem resistance is rare in Vibrio cholerae O1 (VC), the recent emergence of CR strains reveals a concerning shift in their antimicrobial resistance (AMR) landscape. This study aims to characterize the resistance mechanisms in newly identified El Tor CRVC isolated from cholera patients in Gujarat, India during 2019. Fifty VC isolates were screened for major virulence-associated genes along with the determination of their antibiotic resistance profiles using Kirby-Bauer disk diffusion and MIC assays. Whole-genome sequencing (WGS) was employed to investigate the underlying mechanisms of CR. All the isolates exhibited hypervirulent Haitian alleles of major virulence genes and AMR profiles of typical multidrug resistance (MDR). Strikingly, 12% (6/50) of them were resistant to carbapenems and other antibiotics. Molecular analysis revealed that these CR isolates were clonally related and harbored a 142 kbp IncA/C type conjugative mega-plasmid with several AMR encoding genes, including blaNDM-1, that can be easily transferred to other bacterial species and confer donor AMR patterns. The plasmidfs competence for horizontal gene transfer presents a significant risk of dissemination to other enteric pathogens and thereby may complicate the treatment. This finding emphasizes the urgent need for enhanced genomic surveillance and robust antimicrobial stewardship programs aimed at curbing the spread of CRVC strains and mitigating their impact on cholera treatment and containment strategies. en-copyright= kn-copyright= en-aut-name=ShawSreeja en-aut-sei=Shaw en-aut-mei=Sreeja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PragasamAgila Kumari en-aut-sei=Pragasam en-aut-mei=Agila Kumari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=5 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=6 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=7 ORCID= en-aut-name=KariaJigna en-aut-sei=Karia en-aut-mei=Jigna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NinamaGovind en-aut-sei=Ninama en-aut-mei=Govind 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=AkedaYukihiro en-aut-sei=Akeda en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 ORCID= affil-num=1 en-affil=ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=2 en-affil=V. Ramalingaswami Bhawan, Indian Council of Medical Research kn-affil= affil-num=3 en-affil=ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=4 en-affil=ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=5 en-affil=ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=6 en-affil=ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=7 en-affil=ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=8 en-affil=Medical College Baroda kn-affil= affil-num=9 en-affil=Medical College Baroda kn-affil= affil-num=10 en-affil=Okayama University kn-affil= affil-num=11 en-affil=National Institute of Infectious Diseases kn-affil= affil-num=12 en-affil=ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=13 en-affil=ICMR-National Institute for Research in Bacterial Infections kn-affil= en-keyword=antimicrobial resistance kn-keyword=antimicrobial resistance en-keyword=Vibrio cholerae kn-keyword=Vibrio cholerae en-keyword=blaNDM-1 kn-keyword=blaNDM-1 en-keyword=carbapenem resistance kn-keyword=carbapenem resistance en-keyword=horizontal gene transfer kn-keyword=horizontal gene transfer en-keyword=IncA/C plasmid kn-keyword=IncA/C plasmid END start-ver=1.4 cd-journal=joma no-vol=93 cd-vols= no-issue= article-no= start-page=102631 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Detection of the nuclear translocation of androgen receptor using quantitative and automatic cell imaging analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Testosterone signaling mediates diseases such as androgenetic alopecia and prostate cancer and is controlled by the activation of the androgen receptor (AR) and nuclear translocation of the ligand-receptor complex. This study established an immortalized dermal papilla cell line that stably expresses the AR labeled with a monomeric green fluorescence marker. The cells expressed the histone H2B protein as visualized using a red fluorescence marker, enabling the Detection of nuclear translocation under live cell conditions using image analysis. The AR was observed to be translocated from the cytoplasm to the nucleus of cells after stimulation with dihydrotestosterone (DHT). The signal intensity of the nuclear/cytoplasm ratio was analyzed using automatic image analysis and a newly developed algorithm. The quantitation method to detect nuclear translocation revealed that the AR nuclear signal plateaued approximately 20?min after DHT exposure. Our developed method has the potential to save human labor by the automatic process of the image. en-copyright= kn-copyright= en-aut-name=BaiLanlan en-aut-sei=Bai en-aut-mei=Lanlan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WuTao en-aut-sei=Wu en-aut-mei=Tao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukasawaMizuki en-aut-sei=Fukasawa en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KashiwagiSayo en-aut-sei=Kashiwagi en-aut-mei=Sayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TateHaruka en-aut-sei=Tate en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OzakiTaku en-aut-sei=Ozaki en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuganoEriko en-aut-sei=Sugano en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TomitaHiroshi en-aut-sei=Tomita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshiiTsuyoshi en-aut-sei=Ishii en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkashiTakuya en-aut-sei=Akashi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FukudaTomokazu en-aut-sei=Fukuda en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Graduate School of Science and Engineering, Iwate University kn-affil= affil-num=2 en-affil=Graduate School of Science and Engineering, Iwate University kn-affil= affil-num=3 en-affil=Neuro-AI Integration Science Laboratory, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Rohto Pharmaceutical Co., Ltd., Basic Research Development Division kn-affil= affil-num=5 en-affil=Graduate School of Science and Engineering, Iwate University kn-affil= affil-num=6 en-affil=Graduate School of Science and Engineering, Iwate University kn-affil= affil-num=7 en-affil=Graduate School of Science and Engineering, Iwate University kn-affil= affil-num=8 en-affil=Graduate School of Science and Engineering, Iwate University kn-affil= affil-num=9 en-affil=Rohto Pharmaceutical Co., Ltd., Basic Research Development Division kn-affil= affil-num=10 en-affil=Neuro-AI Integration Science Laboratory, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Science and Engineering, Iwate University kn-affil= en-keyword=Dermal papilla cell kn-keyword=Dermal papilla cell en-keyword=Nuclear translocation kn-keyword=Nuclear translocation en-keyword=Androgen receptor kn-keyword=Androgen receptor en-keyword=Live cell imaging kn-keyword=Live cell imaging en-keyword=Digital image analysis kn-keyword=Digital image analysis en-keyword=Quantitation algorithm kn-keyword=Quantitation algorithm END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=1 article-no= start-page=10 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=Gut microbial metabolite butyrate boosts p53-expressing telomerase-specific oncolytic adenovirus efficacy by enhancing infectivity and activating MHC-I/cGAS-STING en-subtitle= kn-subtitle= en-abstract= kn-abstract=The gut microbiota plays an essential role in regulating host immunity, and its metabolites such as butyrate exert immunomodulatory effects by acting as histone deacetylase inhibitors. Oncolytic virotherapy has emerged as a promising approach for cancer treatment, and we have developed OBP-702, a telomerase-specific oncolytic adenovirus that expresses p53 and elicits strong systemic antitumor responses. In this study, the potential synergy between butyrate and OBP-702 was investigated in colorectal cancer models. Using human and murine colorectal carcinoma cell lines, butyrate was found to directly enhance the infectivity of OBP-702 by upregulating CAR and integrins, thereby promoting apoptosis and autophagy in tumor cells. In addition, butyrate indirectly boosted systemic antitumor immunity by upregulating MHC-I expression through activation of the cGAS-STING pathway and enhancing CD8?+?T cell recruitment via CXCL10 secretion. These findings were supported by in vivo experiments using CT26 subcutaneous, bilateral, and orthotopic tumor models, in which the combination of oral butyrate and intratumoral OBP-702 administration produced synergistic antitumor effects. These results highlight the therapeutic potential of integrating gut microbial metabolites with oncolytic virotherapy as a novel immunotherapeutic strategy for colorectal cancer. en-copyright= kn-copyright= en-aut-name=SakamotoMasaki en-aut-sei=Sakamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KatayamaTetsuya en-aut-sei=Katayama en-aut-mei=Tetsuya 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=HanzawaShunya en-aut-sei=Hanzawa en-aut-mei=Shunya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KadowakiDaisuke en-aut-sei=Kadowaki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=HamadaYuki en-aut-sei=Hamada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugimotoRyoma en-aut-sei=Sugimoto en-aut-mei=Ryoma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YagiChiaki en-aut-sei=Yagi en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 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=16 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=17 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=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= 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=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Butyrate kn-keyword=Butyrate en-keyword=Oncolytic adenovirus kn-keyword=Oncolytic adenovirus en-keyword=MHC-I kn-keyword=MHC-I en-keyword=CD8 + T cells kn-keyword=CD8 + T cells en-keyword=Cancer immunotherapy kn-keyword=Cancer immunotherapy END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=3 article-no= start-page=95 end-page=97 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 2024 Incentive Award of the Okayama Medical Association in Cardiovascular and Pulmonary Research (2024 Sunada Prize) kn-title=ߘaUNxRw܁@EzŒ܁ic܁j en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KawanaShinichi en-aut-sei=Kawana en-aut-mei=Shinichi kn-aut-name=얼L kn-aut-sei=얼 kn-aut-mei=L aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=Rww@㎕w ċzEBOȊw END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=3 article-no= start-page=89 end-page=91 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 2024 Incentive Award of the Okayama Medical Association in Cancer Research (2024 Hayashibara Prize and Yamada Prize) kn-title=ߘaUNxRw܁@񌤋܁iь܁ERc܁j en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TakihiraShota en-aut-sei=Takihira en-aut-mei=Shota kn-aut-name=畽 kn-aut-sei=畽 kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=Rww@㎕wȁ@`OȊw END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=1 article-no= start-page=012041 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High-quality welding of copper and aluminum by angled laser irradiation and insert metals en-subtitle= kn-subtitle= en-abstract= kn-abstract=Copper is an important material in order to use electricity effectively, and aluminum is also an attractive material to perform lightweight construction. Laser welding of copper and aluminum is required, and there are some reports to weld copper and aluminum firmly by laser irradiation from the aluminum side. On the other hand, laser irradiation from the copper side requires high power density to generate a keyhole, which causes the strong convection of molten aluminum into copper. Thus, brittle intermetallic compounds with rich aluminum result in the deterioration of joining strength. Angled laser irradiation enables mild heat input to the aluminum side, and the combination of angled and superposed irradiation of blue and near-infrared (NIR) lasers achieved a remarkable increase of breaking strength. However, the breaking strength is still lower than the base materials. Therefore, insert materials between copper and aluminum plates were investigated by the angled irradiation of blue and NIR lasers from the copper side. The breaking strength with insert materials showed higher values in the order of titanium mesh, nickel foil, and nickel mesh, and its value with the nickel mesh was close to the tensile strength of aluminum in a cross tensile test. Further improvement of breaking strength is possible by inserting the nickel mesh between copper and aluminum plates in the case of angled irradiation of blue and NIR lasers even from the copper side. en-copyright= kn-copyright= en-aut-name=OkamotoYasuhiro en-aut-sei=Okamoto en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaYuki en-aut-sei=Yamada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkadaAkira en-aut-sei=Okada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakeMasaki en-aut-sei=Miyake en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamuraTakeshi en-aut-sei=Yamamura en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagasakiKatsutoshi en-aut-sei=Nagasaki en-aut-mei=Katsutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishiNorio en-aut-sei=Nishi en-aut-mei=Norio 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 Environmental, Life, Natural Science and Technology, 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=Kataoka Corporation kn-affil= affil-num=5 en-affil=Kataoka Corporation kn-affil= affil-num=6 en-affil=Kataoka Corporation kn-affil= affil-num=7 en-affil=Kataoka Corporation kn-affil= en-keyword=welding kn-keyword=welding en-keyword=copper kn-keyword=copper en-keyword=aluminum kn-keyword=aluminum en-keyword=insert metal kn-keyword=insert metal en-keyword=intermetallic compound kn-keyword=intermetallic compound en-keyword=fiber laser kn-keyword=fiber laser en-keyword=blue laser kn-keyword=blue laser en-keyword=angled irradiation kn-keyword=angled irradiation END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=11 article-no= start-page=105889 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=Association between adjuvant chemotherapy and outcomes in resected locoregional recurrence of hormone receptor-positive HER2-negative breast cancer: a multi-institutional retrospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: To evaluate the association of adjuvant chemotherapy and prognosis for locoregional recurrence (LRR) in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative subtype breast cancer.
Patients and methods: We carried out a multi-institutional retrospective cohort study in patients with breast cancer who developed HR-positive HER2-negative LRR. Patients who underwent curative surgery for LRR between 2014 and 2018 were categorized based on whether they received adjuvant chemotherapy for LRR (CTx versus no-CTx). Invasive disease-free survival (iDFS) was evaluated between the groups by Cox proportional hazards analysis. The primary analysis used a double-robust Cox model incorporating inverse probability of treatment weighting, and a sensitivity analysis using propensity score matching was also carried out.
Results: A total of 958 patients were included. The median time from the primary surgery to LRR diagnosis was 9.5 years (interquartile range 3.1-10.1 years). There were 235 patients (25%) in the CTx group and 722 (75%) in the no-CTx group. Among all patients, the 5-year iDFS rate was 75.4% [95% confidence interval (CI) 72.4% to 78.2%]. Multivariate analysis showed better iDFS in the CTx group (hazard ratio 0.70, 95% CI 0.49-0.99, P = 0.045). Sensitivity analysis supported these findings. Subgroup analyses showed that the CTx group had better iDFS in cases with non-ipsilateral breast tumor recurrence (IBTR), recurrences during adjuvant endocrine therapy for primary breast cancer, and without perioperative chemotherapy for primary breast cancer. Secondary analysis showed no significant difference with a worse trend toward overall survival in the CTx group with multivariate Cox proportional hazards analysis.
Conclusion: Adjuvant chemotherapy for HR-positive HER2-negative LRR was associated with better iDFS, particularly in cases of non-IBTR, recurrences during adjuvant endocrine therapy, and no prior perioperative chemotherapy for their primary tumor. However, the retrospective design and inability to distinguish true recurrences from new primary tumors in IBTR warrant cautious interpretation. en-copyright= kn-copyright= en-aut-name=OzakiY. en-aut-sei=Ozaki en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TokudaE. en-aut-sei=Tokuda en-aut-mei=E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SagaraY. en-aut-sei=Sagara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaraF. en-aut-sei=Hara en-aut-mei=F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SasadaS. en-aut-sei=Sasada en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SawakiM. en-aut-sei=Sawaki en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KanbayashiC. en-aut-sei=Kanbayashi en-aut-mei=C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamanakaT. en-aut-sei=Yamanaka en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OnishiT. en-aut-sei=Onishi en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujikiY. en-aut-sei=Fujiki en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SutoA. en-aut-sei=Suto en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakahashiY. en-aut-sei=Takahashi en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TokunagaE. en-aut-sei=Tokunaga en-aut-mei=E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ArugaT. en-aut-sei=Aruga en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakamuraR. en-aut-sei=Nakamura en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujisawaT. en-aut-sei=Fujisawa en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SajiS. en-aut-sei=Saji en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IwataH. en-aut-sei=Iwata en-aut-mei=H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShienT. en-aut-sei=Shien en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=2 en-affil=Department of Medical Oncology, Fukushima Medical University kn-affil= affil-num=3 en-affil=Department of Breast Surgery, Social Medical Corporation Hakuaikai Sagara Hospital kn-affil= affil-num=4 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University kn-affil= affil-num=6 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=7 en-affil=Department of Breast Oncology, Niigata Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Breast Surgery and Oncology, Kanagawa Cancer Center kn-affil= affil-num=9 en-affil=Department of Breast Oncology, National Cancer Center Hospital East kn-affil= affil-num=10 en-affil=Department of Breast Surgery, Social Medical Corporation Hakuaikai Sagara Hospital kn-affil= affil-num=11 en-affil=Department of Breast Oncology, National Cancer Center Hospital kn-affil= affil-num=12 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Breast Oncology, National Hospital Organization Kyushu Cancer Center kn-affil= affil-num=14 en-affil=Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=15 en-affil=Division of Breast Surgery, Chiba Cancer Center kn-affil= affil-num=16 en-affil=Department of Breast Oncology, Gunma Prefectural Cancer Center kn-affil= affil-num=17 en-affil=Department of Medical Oncology, Fukushima Medical University kn-affil= affil-num=18 en-affil=Department of Advanced Clinical Research and Development, Nagoya City University kn-affil= affil-num=19 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=locoregional recurrence kn-keyword=locoregional recurrence en-keyword=adjuvant chemotherapy kn-keyword=adjuvant chemotherapy en-keyword=inverse probability of treatment weighting kn-keyword=inverse probability of treatment weighting END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=12 article-no= start-page=1811 end-page=1825 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250926 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of Fentanyl-Emerged Adverse Events and Pharmacokinetics in Neonates: A Physiologically Based Pharmacokinetic Modeling Approach en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Despite its common use for analgesia in neonatal intensive care units, the optimal dosing and safety profile of fentanyl, particularly regarding suspected fentanyl-emerged adverse events (FEAEs), such as hypotension, desaturation, and oliguria, are not well-defined.
Objective This study aimed to develop an optimal therapeutic monitoring and dosing strategy for fentanyl for neonates. A physiologically based pharmacokinetic (PBPK) model for predicting fentanyl pharmacokinetics across various populations, including preterm and term neonates, was developed, and the relationship between predicted fentanyl exposure and FEAE incidence in neonates was assessed.
Methods A PBPK model was developed and validated against the observed values in the literature. The modelfs predictive accuracy for fentanyl pharmacokinetics and association with FEAE incidence in an external retrospective cohort of Japanese neonates was evaluated using the predicted concentrations and pharmacokinetic parameters estimated by PBPK simulation.
Results The PBPK model exhibited reasonable predictive performance for serum fentanyl concentrations in actual neonatal patients (mean error: 9.27% [standard error: 5.06%], root mean squared error: 54.7%). The incidence of any FEAE, particularly oxygen desaturation, was associated with the fentanyl concentration-to-dose ratio, but not with some exposure parameters, such as the area under the curve and maximum concentration. The recommended reduced infusion rate allowed serum fentanyl concentrations to fall within the ranges established by the reported values and our data.
Conclusions Our PBPK model and proposed dosing strategy may contribute to safer and more effective fentanyl use in neonates. en-copyright= kn-copyright= en-aut-name=MahdyWalaa Yousef Bassyouni en-aut-sei=Mahdy en-aut-mei=Walaa Yousef Bassyouni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JojiRisa en-aut-sei=Joji en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HashimotoMari en-aut-sei=Hashimoto en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakasoneRuka en-aut-sei=Nakasone en-aut-mei=Ruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiokaKazumichi en-aut-sei=Fujioka en-aut-mei=Kazumichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItoharaKotaro en-aut-sei=Itohara en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KitahiroYumi en-aut-sei=Kitahiro en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OmuraTomohiro en-aut-sei=Omura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YanoIkuko en-aut-sei=Yano en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=2 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=4 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Graduate School of Medicine, Kobe University kn-affil= affil-num=6 en-affil=Department of Pediatrics, Graduate School of Medicine, Kobe University kn-affil= affil-num=7 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=8 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=9 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=10 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=1 article-no= start-page=69 end-page=84 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=P53-Armed Oncolytic Virotherapy Promotes the Efficacy of PD1 Blockade in Murine Osteosarcoma Tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Osteosarcoma (OS) is refractory to immune checkpoint inhibitors targeting programmed cell death 1 (PD1)/PD ligand 1 (PD-L1) due to poor immune response. We previously developed telomerase-specific, replication-competent oncolytic adenoviruses non-armed OBP-301 and P53-armed OBP-702 that exert antitumor efficacy against human OS cells. Recently, we demonstrated that P53-armed OBP-702 induces more profound immunogenic cell death and antitumor immune response against human and murine OS cells than does non-armed OBP-301. In the present study, we assessed the combined efficacy of PD1 blockade and P53-armed OBP-702 against murine OS cells.
Materials and Methods: Three murine OS cell lines (K7M2, NHOS, NHOS-LM4) were used to assess the cytopathic effect of non-armed OBP-301 and P53-armed OBP-702 by XTT assay. Virus-induced immunogenic cell death was assessed by analyzing the levels of extracellular adenosine triphosphate and high-mobility group box protein B1. The expression of PD-L1 and PD-L2 was analyzed by flow cytometry. The malignant potential of NHOS-LM4 cells was analyzed by a migration and invasion assay. An orthotopic NHOS-LM4 tumor model was used to evaluate the antitumor efficacy of combination therapy with P53-armed OBP-702 and anti-PD1.
Results: P53-armed OBP-702 exhibited antitumor potential for the induction of immunogenic cell death, apoptosis, autophagy, and PD-L1/2 upregulation in K7M2 and NHOS cells. NHOS-LM4 cells showed increased migratory and invasive ability compared to NHOS cells. P53-armed OBP-702 significantly suppressed the malignant potential of NHOS-LM4 cells. Combination dosing showed that P53-armed OBP-702 significantly promoted the antitumor effect of PD1 blockade against NHOS-LM4 tumors.
Conclusion: Our results suggest that P53-armed OBP-702 is a promising agent for improving the antitumor effect of PD1 blockade in treating invasive OS. en-copyright= kn-copyright= en-aut-name=KUREMIHO en-aut-sei=KURE en-aut-mei=MIHO 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=DEMIYAKOJI en-aut-sei=DEMIYA en-aut-mei=KOJI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=MOCHIZUKIYUSUKE en-aut-sei=MOCHIZUKI en-aut-mei=YUSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KOMATSUBARATADASHI en-aut-sei=KOMATSUBARA en-aut-mei=TADASHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=UOTANIKOJI en-aut-sei=UOTANI en-aut-mei=KOJI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 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=12 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=13 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=14 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=15 ORCID= affil-num=1 en-affil=Department of Orthopaedic 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 Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Orthopaedic 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= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Osteosarcoma kn-keyword=Osteosarcoma en-keyword=oncolytic adenovirus kn-keyword=oncolytic adenovirus en-keyword=P53 kn-keyword=P53 en-keyword=immunogenic cell death kn-keyword=immunogenic cell death en-keyword=PD1 kn-keyword=PD1 END