start-ver=1.4 cd-journal=joma no-vol=48 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20261030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=岡山大学環境管理センター報　第48号 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=岡山大学安全衛生推進機構環境管理部門 kn-aut-sei=岡山大学安全衛生推進機構環境管理部門 kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=170 cd-vols= no-issue=4 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Preexisting Schizophrenia Spectrum Disorders on the Receipt of Surgery and Other Treatments for Non-Small Cell Lung Cancer: A Multicenter Nationwide Cohort Study in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Patients with schizophrenia spectrum disorders (SSDs) experience higher cancer mortality than the general population. Disparities in treatments for non-small cell lung cancer (NSCLC) among this population remain underexamined.
Research Question: Are patients with SSDs less likely to receive surgery, adjuvant chemotherapy for stage II/IIIA, concurrent chemoradiotherapy for stage III, and systemic therapy for stage IV NSCLC compared with those without psychiatric disorders?
Study Design and Methods: This retrospective cohort study used national Hospital-Based Cancer Registry data linked to hospital-based administrative data in Japan. It included patients who received initial treatment for NSCLC between 2018 and 2021. Presence of SSDs was defined as a diagnosis using F20 to F29 codes from International Classification of Diseases, 10th Revision. The primary outcome was receipt of surgery for NSCLC. Secondary outcomes were receipt of the following: (1) adjuvant chemotherapy within 180 days in patients with pathologic stage II/IIIA NSCLC; (2) concurrent chemoradiotherapy in clinical stage III NSCLC; and (3) systemic therapy in stage IV NSCLC. Multivariable logistic regression adjusted for age, sex, clinical stage, comorbidities, and functional status was performed.
Results: The final cohort comprised 166,663 patients, 1,346 of whom had SSDs. Patients with SSDs were more likely to be diagnosed at stage IV NSCLC (45.0% vs 31.4%) and less likely to undergo surgery (31.5% vs 49.9%; adjusted OR [aOR], 0.70; 95% CI, 0.57-0.85), receive adjuvant chemotherapy (aOR, 0.31; 95% CI, 0.17-0.57), or receive systemic therapy (aOR, 0.54; 95% CI, 0.45-0.65). No significant difference was observed in concurrent chemoradiotherapy for stage III NSCLC (aOR, 0.99; 95% CI, 0.73-1.34).
Interpretation: Patients with SSDs were less likely to receive surgery and other stage-appropriate treatments for NSCLC, highlighting the need for targeted interventions to promote equitable cancer care for these individuals. en-copyright= kn-copyright= en-aut-name=YamadaYuto en-aut-sei=Yamada en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=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=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki 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, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Medical Development Field, Okayama University 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=Center for Clinical Oncology, Okayama University Hospital 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=cancer care disparity kn-keyword=cancer care disparity en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=schizophrenia spectrum disorders kn-keyword=schizophrenia spectrum disorders END start-ver=1.4 cd-journal=joma no-vol=48 cd-vols= no-issue=1 article-no= start-page=47 end-page=57 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241011 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of different ANCA detection methods in a predominantly MPO-ANCA-associated vasculitis cohort en-subtitle= kn-subtitle= en-abstract= kn-abstract=We compared different antineutrophil cytoplasmic antibody (ANCA) detection methods using a predominantly myeloperoxidase (MPO)-ANCA-associated vasculitis cohort. Stored sera from 147 patients with untreated ANCA-associated vasculitis (AAV), including microscopic polyangiitis and granulomatosis with polyangiitis (n?=?115 and 32, respectively), and 124 disease controls were tested for P-ANCA and C-ANCA with immunofluorescence (IIF), and for MPO-ANCA and proteinase 3 (PR3)-ANCA with different antigen-specific immunoassays: direct enzyme-linked immunosorbent assay (ELISA), chemiluminescent enzyme immunoassay (CLEIA), third-generation fluorescent enzyme immunoassay (FEIA), and latex turbidimetrical immunoassay (LTIA). In addition, MPO-ANCA and PR3-ANCA titers were calibrated using certified reference materials (CRMs). The sensitivities and specificities for AAV diagnoses were 95% and 94% (IIF), 86% and 98% (ELISA), 93% and 94% (CLEIA), 92% and 96% (FEIA), and 68% and 88% (LTIA). Dual IIF/antigen-specific immunoassay testing reduced diagnostic accuracies from 94% to 93%. The quantitative agreement between ANCA levels measured using CLEIA and FEIA and calibrated using CRMs was not good. In conclusion, this study demonstrated the high performance of antigen-specific immunoassays for AAV diagnosis in a predominantly MPO-ANCA-associated vasculitis cohort and suggested that the benefit of dual IIF/antigen-specific immunoassay testing is limited. Standardizing ANCA measurements using different immunoassays was difficult, even when using CRMs. en-copyright= kn-copyright= en-aut-name=KatsumataYasuhiro en-aut-sei=Katsumata en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KamedaTomohiro en-aut-sei=Kameda en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DobashiHiroaki en-aut-sei=Dobashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanameShinya en-aut-sei=Kaname en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsuboiNaotake en-aut-sei=Tsuboi en-aut-mei=Naotake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=AmanoKoichi en-aut-sei=Amano en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TamuraNaoto en-aut-sei=Tamura en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HarigaiMasayoshi en-aut-sei=Harigai en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=Research Committee of Intractable Vasculitis Syndrome and the Research Committee of Intractable Renal Disease of the Ministry of Health, Labour and Welfare of Japan en-aut-sei=Research Committee of Intractable Vasculitis Syndrome and the Research Committee of Intractable Renal Disease of the Ministry of Health, Labour and Welfare of Japan en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Division of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University School of Medicine 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 Rheumatology, Takamatsu Red Cross Hospital kn-affil= affil-num=4 en-affil=Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University kn-affil= affil-num=5 en-affil=Department of Nephrology and Rheumatology, Kyorin University School of Medicine kn-affil= affil-num=6 en-affil=Department of Nephrology, Fujita Health University School of Medicine 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= affil-num=8 en-affil=Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=9 en-affil=Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine kn-affil= affil-num=10 en-affil=Division of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University School of Medicine kn-affil= affil-num=11 en-affil= kn-affil= en-keyword=Antineutrophil cytoplasm antibody kn-keyword=Antineutrophil cytoplasm antibody en-keyword=microscopic polyangiitis kn-keyword=microscopic polyangiitis en-keyword=granulomatosis with polyangiitis kn-keyword=granulomatosis with polyangiitis en-keyword=laboratory diagnosis kn-keyword=laboratory diagnosis END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=5 article-no= start-page=e70124 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Direct and Element‐Mediated Edaphic Effects Shape Resource‐Conservative Leaf Trait Variation Across Serpentine and Limestone Soils en-subtitle= kn-subtitle= en-abstract= kn-abstract=Edaphically extreme substrates, such as serpentine and limestone, impose strong physiological constraints on plants and are frequently associated with resource-conservative leaf traits and narrow plant endemism. However, it remains unclear how edaphic selection shapes leaf traits and whether these shifts are driven primarily by direct soil-imposed constraints or indirectly by changes in leaf elemental composition. Here, we examined soil?leaf elemental relationships, leaf functional traits, and CSR strategies (Competitive, Stress-tolerant, and Ruderal strategy) using piecewise structural equation modeling across 16 populations of five closely related Epimedium taxa distributed on serpentine, limestone, and other substrates in western Japan. Despite marked differences in soil and leaf elemental composition between serpentine and limestone sites, populations on both substrates converged toward resource-conservative leaf traits, including lower specific leaf area (SLA) and a shift toward thicker leaves and higher leaf dry matter content (LDMC), even after accounting for species identity. Piecewise structural equation modeling revealed two pathways consistent with the proposed hypotheses: A strong direct association between soil elemental composition and leaf trait variation and a weaker indirect association involving leaf elemental composition. Together, our results suggest that edaphic mosaics are linked to convergent resource-conservative phenotypes through two partly overlapping pathways across serpentine and limestone soils: strong direct associations with leaf functional traits and weaker associations involving leaf elemental composition. en-copyright= kn-copyright= en-aut-name=UeyamaShogo en-aut-sei=Ueyama en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KusatakeEmi en-aut-sei=Kusatake en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MimuraMakiko en-aut-sei=Mimura en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Biology, Okayama University kn-affil= affil-num=2 en-affil=Department of Biology, Okayama University kn-affil= affil-num=3 en-affil=Department of Biology, Okayama University kn-affil= en-keyword=CSR scheme kn-keyword=CSR scheme en-keyword=edaphic stress kn-keyword=edaphic stress en-keyword=leaf economics spectrum kn-keyword=leaf economics spectrum en-keyword=stress tolerance kn-keyword=stress tolerance en-keyword=trait convergence kn-keyword=trait convergence END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=2709258 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260816 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rotavirus-NSP5 interacts with and hijacks host ATP citrate lyase to viroplasms, enhancing lipid biosynthesis for facilitating rotavirus infection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rotavirus (RV) replication occurs within viroplasms (VMs) and is initiated by two RV non-structural proteins NSP2 and NSP5. Viruses exploit host cellular components for their replication and assembly; however, information on the roles of host proteins in VM dynamics and RV replication is limited. Thus, in the current study, we used proteomics to identify host proteins that interact with NSP5 during RV infection to delineate their role in virus replication. A large number of host proteins (n?=?128) were found to interact with NSP5, and Gene Ontology enrichment analysis revealed the enrichment of various metabolic processes during RV infection. One of the essential host proteins, ATP citrate lyase (ACLY), which is involved in the de novo lipid synthesis pathway, was found to interact with C-terminal region of RV-NSP5 and colocalize within VMs. Following RV infection, the serine 455 phosphorylation of ACLY was induced, suggesting increased enzymatic activation. This correlates with enhanced lipid droplet production via increased acetyl-coenzyme A expression levels, which in turn supports VM formation. The ACLY inhibitors SB204990 or hydroxycitric acid tripotassium hydrate significantly reduced RV-infection in vitro. This anti-rotaviral effect of drug was further validated in BALB/c suckling mice by measuring viral protein expression and viral titers. In the presence of ACLY inhibitor, reduced viral titers, reduced viral protein expression, and improved small intestinal histopathology were observed. These findings suggest a protective effect of drugs against RV infection in vivo and highlight ACLY as a potential anti-rotaviral target for the development of new therapeutics. en-copyright= kn-copyright= en-aut-name=SharmaRanjana en-aut-sei=Sharma en-aut-mei=Ranjana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BanerjeeShreya en-aut-sei=Banerjee en-aut-mei=Shreya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChaudhuriRatul Datta en-aut-sei=Chaudhuri en-aut-mei=Ratul Datta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DeyKaushik Kumar en-aut-sei=Dey en-aut-mei=Kaushik Kumar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ImamuraDaisuke en-aut-sei=Imamura en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Chawla-SarkarMamta en-aut-sei=Chawla-Sarkar en-aut-mei=Mamta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Regional VRDL, ICMR- National Institute for Research in Bacterial Infections (formerly ICMR-NICED) kn-affil= affil-num=2 en-affil=Regional VRDL, ICMR- National Institute for Research in Bacterial Infections (formerly ICMR-NICED) kn-affil= affil-num=3 en-affil=Regional VRDL, ICMR- National Institute for Research in Bacterial Infections (formerly ICMR-NICED) kn-affil= affil-num=4 en-affil=Division of Applied Biosciences, ICMR- National Institute for Research in Bacterial Infections (Formerly ICMR-NICED) kn-affil= affil-num=5 en-affil=Department of Central Instrumental Facility, ICMR- National Institute for Research in Bacterial Infections (Formerly ICMR-NICED) kn-affil= affil-num=6 en-affil=ICMR- National Institute for Research in Bacterial Infections (Formerly ICMR-NICED), Collaborative Research Center of Okayama University for Infectious Diseases in India kn-affil= affil-num=7 en-affil=ICMR- National Institute for Research in Bacterial Infections (Formerly ICMR-NICED), Collaborative Research Center of Okayama University for Infectious Diseases in India kn-affil= affil-num=8 en-affil=Regional VRDL, ICMR- National Institute for Research in Bacterial Infections (formerly ICMR-NICED) kn-affil= en-keyword=Rotavirus kn-keyword=Rotavirus en-keyword=viroplasm kn-keyword=viroplasm en-keyword=non-structural protein 5 (NSP5) kn-keyword=non-structural protein 5 (NSP5) en-keyword=proteomics kn-keyword=proteomics en-keyword=host-pathogen interaction kn-keyword=host-pathogen interaction en-keyword=ATP citrate lyase kn-keyword=ATP citrate lyase END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=76 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sequence and timing of organ donation discussions in brain-dead donors: a subanalysis of the J-RESPECT study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The optimal timing of organ donation discussions in patients with catastrophic brain injury remains unclear. In Japan, national guidance recommends providing information after recognition of a state compatible with brain death; however, real-world practice has not been well characterized. This study aimed to evaluate the sequence of organ donation option presentation relative to clinical determination of a brain death-compatible state and to assess option presentation timing.
Methods We conducted a multicenter retrospective cohort study using data from the J-RESPECT study, including adult brain-dead donors from 16 institutions in Japan between 2010 and 2023. Donors were classified as brain death-first (option presented after clinical determination of a brain death-compatible state) or option-first (option presented before such determination). Mixed-effects logistic and linear regression models with random intercepts for institution were used to examine factors associated with presentation sequence and timing.
Results Among 190 donors, 76 (40%) were classified as brain death-first and 114 (60%) as option-first. In mixed-effects logistic regression, age was the only independent factor associated with presentation sequence (adjusted OR 1.03 per year, 95% CI 1.00?1.07), while substantial between-institution variability was observed (intraclass correlation coefficient?=?0.32). Institutional timing policy was not significantly associated with presentation sequence. The median interval from admission to option presentation was 5 days in the brain death-first group and 2 days in the option-first group (p? Conclusions Substantial inter-institutional variability exists in the sequence and timing of organ donation discussions in Japan. Further studies are needed to determine optimal approaches to organ donation communication and timing in clinical practice. en-copyright= kn-copyright= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=HayakawaMineji en-aut-sei=Hayakawa en-aut-mei=Mineji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=NishiyamaKei en-aut-sei=Nishiyama en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AtsumiTakahiro en-aut-sei=Atsumi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TasakiOsamu en-aut-sei=Tasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsurukiriJunya en-aut-sei=Tsurukiri en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HayamizuMariko en-aut-sei=Hayamizu en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MurahashiShimon en-aut-sei=Murahashi en-aut-mei=Shimon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayashiMunehiro en-aut-sei=Hayashi en-aut-mei=Munehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NishimuraTakeshi en-aut-sei=Nishimura en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=GotoYukari en-aut-sei=Goto en-aut-mei=Yukari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NarumiyaHiromichi en-aut-sei=Narumiya en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MizutaniAtsushi en-aut-sei=Mizutani en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MiyajimaMamoru en-aut-sei=Miyajima en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ShimazakiJunya en-aut-sei=Shimazaki en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MiuraTakeshi en-aut-sei=Miura en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShimaNozomu en-aut-sei=Shima en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=DeuchiKazuki en-aut-sei=Deuchi en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NakayasuHitomi en-aut-sei=Nakayasu en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KanoHitoshi en-aut-sei=Kano en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 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=23 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=24 ORCID= en-aut-name=J-RESPECT study group en-aut-sei=J-RESPECT study group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University 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 Medicine, Hokkaido University Hospital kn-affil= affil-num=4 en-affil=Department of Emergency Medicine, Hokkaido University Hospital kn-affil= affil-num=5 en-affil=Division of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental Science kn-affil= affil-num=6 en-affil=Department of Emergency and Disaster Medicine, Hamamatsu University School of Medicine kn-affil= affil-num=7 en-affil=Acute and Critical Care Center, Nagasaki University Hospital kn-affil= affil-num=8 en-affil=Emergency and Critical Care Medicine, Tokyo Medical University Hachioji Medical Center kn-affil= affil-num=9 en-affil=Department of Emergency Medicine, Hokkaido University Hospital kn-affil= affil-num=10 en-affil=Acute and Critical Care Center, Nagasaki University Hospital kn-affil= affil-num=11 en-affil=Department of Emergency and Critical Care Medicine, Japanese Red Cross Medical Center kn-affil= affil-num=12 en-affil=Department of Emergency and Critical Care Medicine, Hyogo Emergency Medical Center kn-affil= affil-num=13 en-affil=Department of Emergency Medicine, Nagoya Ekisaikai Hospital kn-affil= affil-num=14 en-affil=Department of Emergency and Critical Care Medicine, Japanese Red Cross Kyoto Daini Hospital kn-affil= affil-num=15 en-affil=Department of Emergency Medicine, Hamamatsu Medical Center kn-affil= affil-num=16 en-affil=Emergency and Critical Care Center, Nagaoka Red Cross Hospital kn-affil= affil-num=17 en-affil=Department of Emergency and Critical Care Medicine, Kansai Medical University Medical Center kn-affil= affil-num=18 en-affil=Department of Emergency and Critical Care Medicine, Institute of Medicine, University of Tsukuba Hospital kn-affil= affil-num=19 en-affil=Department of Emergency and Critical Care Medicine, Wakayama Medical University kn-affil= affil-num=20 en-affil=Division of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental Science kn-affil= affil-num=21 en-affil=Emergency and Critical Care Medicine, Seirei Hamamatsu General Hospital kn-affil= affil-num=22 en-affil=Department of Emergency Medicine, Hokkaido University Hospital kn-affil= affil-num=23 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=24 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=25 en-affil= kn-affil= en-keyword=Brain death kn-keyword=Brain death en-keyword=Communication kn-keyword=Communication en-keyword=Decision-making kn-keyword=Decision-making en-keyword=End-of-life care kn-keyword=End-of-life care en-keyword=Intensive care kn-keyword=Intensive care en-keyword=Organ donation kn-keyword=Organ donation END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=674 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260618 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Timing of emergency department presentation and psychiatric consultation after self-harm or suicide attempts: a registry-based study in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Self-harm and suicide attempts are frequent causes of emergency department (ED) visits and are strongly associated with an elevated suicide risk. Early psychiatric evaluation in the ED can help reduce repeated self-harm; however, the relationship between presentation timing and psychiatric consultations remains unclear. This study aimed to explore the association between ED visit timing and the likelihood of psychiatric referrals among patients presenting with self-harm or suicide attempts in Japan.
Methods This multicenter, registry-based cohort study analyzed data from the JAPAN Registry of Self-Harm and Suicide Attempt from December 1, 2022, to December 31, 2023. Patients presenting to EDs with intentional self-harm or suicide attempts were included. The primary outcome was psychiatric consultation within one day of presentation, analyzed by day and time of presentation using multiple logistic regression, adjusting for potential confounders.
Results Of the 1,721 patients analyzed, the median age was 33 years, and 1,127 (65.5%) were female. A total of 1,199 patients (69.7%) received psychiatric consultations, while 522 (30.3%) did not receive a consultation within the next day after presentation. Hospital presentations on Saturdays (adjusted OR, 0.39; 95% CI, 0.20?0.75) and during 4 p.m. to 8 p.m. (adjusted OR, 0.47; 95% CI, 0.24?0.91) were associated with lower likelihoods of psychiatric consultations, using Monday and the 8 a.m. to 12 p.m. period as the reference, respectively.
Conclusions Hospital presentations on Saturdays or evening hours were associated with reduced likelihoods of psychiatric consultations, highlighting disparities in access to care during off-hours. These findings may help inform efforts to improve resource allocation and flexible staffing to ensure timely and consistent psychiatric care in ED settings.
Clinical trial number Not applicable. en-copyright= kn-copyright= en-aut-name=JinnoShunta en-aut-sei=Jinno en-aut-mei=Shunta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=YakushijiHiromasa en-aut-sei=Yakushiji en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 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=8 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=9 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University 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= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Graduate School of Medical Sciences, Kumamoto University kn-affil= affil-num=8 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Drug overdose kn-keyword=Drug overdose en-keyword=Emergency department kn-keyword=Emergency department en-keyword=Psychiatry kn-keyword=Psychiatry en-keyword=Referral and consultation kn-keyword=Referral and consultation en-keyword=Suicide kn-keyword=Suicide END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=20 article-no= start-page=3418 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20261020 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association Between Urine pH and Kidney Outcomes in Patients with Biopsy-Proven Kidney Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Lower urine pH has been associated with reduced kidney function and increased risk of kidney disease, but its prognostic and pathological significance in biopsy-proven kidney disease remains unclear. Medullary cast formation has been shown to predict adverse renal outcomes beyond cortical interstitial fibrosis and tubular atrophy (IFTA), although its clinical determinants are not fully understood. We examined the associations of urine pH with kidney outcomes and medullary cast formation in patients undergoing native kidney biopsy. Methods: Among 1167 adults who underwent native kidney biopsy between 2011 and 2024, 503 patients with evaluable medullary tissue were included. Urine pH was analyzed in relation to clinical and histological variables and kidney outcomes. The primary outcome was a ?40% decline in estimated glomerular filtration rate (eGFR) or initiation of renal replacement therapy. Results: Mean baseline eGFR was 60.7 ± 26.2 mL/min/1.73 m2 and urine pH was 6.15 ± 0.84. During a median follow-up of 2.11 years, 113 patients (22.5%) reached the outcome. Lower urine pH was associated with higher risk of kidney outcomes. In multivariable Cox models, urine pH remained independently associated with outcomes (hazard ratio per 1-unit increase, 0.69; 95% CI, 0.52?0.92). Addition of urine pH modestly improved discrimination (C-index 0.642 to 0.654; likelihood ratio test, p = 0.009). Lower urine pH was associated with greater medullary cast formation in unadjusted analysis. Conclusions: Lower urine pH was independently associated with adverse kidney outcomes and with greater medullary cast formation, suggesting that urine pH may reflect intratubular pathological changes associated with CKD progression. en-copyright= kn-copyright= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueYoshitaka en-aut-sei=Inoue en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=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=urine pH kn-keyword=urine pH en-keyword=kidney outcomes kn-keyword=kidney outcomes en-keyword=medullary casts kn-keyword=medullary casts en-keyword=global glomerulosclerosis kn-keyword=global glomerulosclerosis en-keyword=interstitial fibrosis and tubular atrophy kn-keyword=interstitial fibrosis and tubular atrophy END start-ver=1.4 cd-journal=joma no-vol=61 cd-vols= no-issue=3 article-no= start-page=895 end-page=902 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=A Comparative Analysis of the CID Pilot Program, Special Rate-Based BIDs, and Voluntary Membership?Based BIDs - A case study of New South Wales, Australia - kn-title=CIDパイロットプロジェクトとSpecial Rate型BIDおよび寄付金型BIDの比較分析 -オーストラリア・ニューサウスウェールズ州を対象として- en-subtitle= kn-subtitle= en-abstract=Japanese Area Management Levy System stagnates due to high consensus hurdles. This study investigates the multilayered BID framework in New South Wales, Australia, to derive implications for Japan. Research findings reveal that system selection depends on city scale: government-led "Special Rate" models are predominant in regional areas, while private-sector-led "CID Projects" or "Membership-type BIDs" are favored in urban centers. Based on these insights, this paper proposes a phased transition model for Japan that facilitates a shift from administration-led structures to private-authority systems as local organizational capacity matures. Enabling flexible, scale-appropriate choices is essential for lowering implementation barriers and revitalizing area management activities in Japanese cities. kn-abstract=日本のエリアマネジメント負担金制度は、合意形成に要する高い同意要件が原因で停滞している。本研究は、オーストラリア・ニューサウスウェールズ州における三類型のBID（Business　Improvement District）を調査し、日本のエリアマネジメント活動の改善に資する提案を行うことを目的とする。調査の結果、制度は都市規模に応じて活用されていることが明らかとなった。地方都市では行政が主な権限を要する「Special Rate型BID」が展開されている一方、都市部では民間側が主な権限を要する「CIDパイロットプロジェクト」や「寄付金型BID」が展開されている。これらの知見に基づき、本論文は、地域の組織能力の成熟度に合わせて行政主導から民間主体へと体制を移行させる「段階的移行モデル」を提案する。柔軟かつ都市規模に適した制度選択を可能にすることは、導入障壁を下げ、日本の都市におけるエリアマネジメント活動を活性化させる上で不可欠である。 en-copyright= kn-copyright= en-aut-name=HoriHirofumi en-aut-sei=Hori en-aut-mei=Hirofumi kn-aut-name=堀裕典 kn-aut-sei=堀 kn-aut-mei=裕典 aut-affil-num=1 ORCID= en-aut-name=KitanoTatsuya en-aut-sei=Kitano en-aut-mei=Tatsuya kn-aut-name=北野達也 kn-aut-sei=北野 kn-aut-mei=達也 aut-affil-num=2 ORCID= affil-num=1 en-affil=Okayama University kn-affil=岡山大学学術研究院環境生命自然科学学域 affil-num=2 en-affil=Okayama University kn-affil=岡山大学大学院環境生命自然科学研究科 en-keyword=BID kn-keyword=BID en-keyword=エリアマネジメント (Area Based Management) kn-keyword=エリアマネジメント (Area Based Management) en-keyword=地域再生エリアマネジメント負担金制度 (Japanese BID System) kn-keyword=地域再生エリアマネジメント負担金制度 (Japanese BID System) en-keyword=地方都市 (Regional Cities) kn-keyword=地方都市 (Regional Cities) en-keyword=Special Rate kn-keyword=Special Rate END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=5 article-no= start-page=327 end-page=332 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ruptured Intrahepatic Arterial Aneurysm due to Segmental Arterial Mediolysis Treated with Coil Embolization en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 67-year-old man presented with sudden-onset abdominal pain and hemorrhagic shock. Contrast-enhanced CT revealed a large hematoma in hepatic segments VI-VII with capsular rupture and hemoperitoneum. CT angiography demonstrated a saccular pseudoaneurysm in a posterior segmental branch of the right hepatic artery and a beaded appearance with irregular dilatation and segmental narrowing of the right hepatic artery branches, without inflammatory or atherosclerotic findings, supporting a diagnosis of segmental arterial mediolysis (SAM). Emergency angiography followed by coil embolization achieved hemostasis. Follow-up CT at 5 months showed complete exclusion of the aneurysmal lesions, with no evidence of recurrence or new vascular lesions. Coil embolization may be an effective, minimally invasive option for ruptured intrahepatic SAM lesions. en-copyright= kn-copyright= en-aut-name=HataYurika en-aut-sei=Hata en-aut-mei=Yurika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TabuchiMotoyasu en-aut-sei=Tabuchi en-aut-mei=Motoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakamotoShinya en-aut-sei=Sakamoto en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TamuraShuta en-aut-sei=Tamura en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UemuraSunao en-aut-sei=Uemura en-aut-mei=Sunao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TokumaruTeppei en-aut-sei=Tokumaru en-aut-mei=Teppei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshimatuRika en-aut-sei=Yoshimatu en-aut-mei=Rika 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 Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=7 en-affil=Department of Radiology, Kochi Health Sciences Center kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= en-keyword=segmental arterial mediolysis kn-keyword=segmental arterial mediolysis en-keyword=hepatic artery kn-keyword=hepatic artery en-keyword=intra-abdominal hemorrhage kn-keyword=intra-abdominal hemorrhage END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=5 article-no= start-page=317 end-page=325 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Radiogenomic Analysis of Contrast-Enhanced MRI for Predicting Pathogenic BRCA Variants in Ovarian Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study evaluated the feasibility of predicting pathogenic BRCA1/2 variants in ovarian cancer using radiogenomic analysis of contrast-enhanced MRI. Twenty six patients were analyzed, including 14 with pathogenic BRCA1/2 variants and 12 without. Contrast enhanced MRI was used to generate two dimensional (2D) and three dimensional (3D) tumor segmentations. Radiomic features extracted with PyRadiomics were reduced using least absolute shrinkage and selection operator (LASSO) regression, yielding two selected features. Linear discriminant analysis (LDA) models were trained on 18 patients and tested on 8, with performance assessed using sensitivity, specificity, accuracy, and the area under the receiver operating characteristic (ROC) curve. The DeLong test compared AUCs between segmentation methods. Automated machine learning (AutoML) was performed with a training set of 20 patients and a test set of 6, with multiple performance metrics calculated. LDA achieved approximately 60% accuracy in both 2D and 3D test datasets. AUCs were 0.80 (3D) and 0.77 (2D), with no significant difference (p=0.85). AutoML identified CatBoost_BAG_L2_FULL as the optimal model, achieving accuracy above 80%. MRI-based radiogenomic analysis demonstrated moderate classification performance for identifying pathogenic BRCA1/2 variants in ovarian cancer. These preliminary findings suggest a potential role for noninvasive prediction, warranting further validation in larger cohorts. en-copyright= kn-copyright= en-aut-name=SaitoHayato en-aut-sei=Saito en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukuiRyohei en-aut-sei=Fukui en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugiharaHanako en-aut-sei=Sugihara en-aut-mei=Hanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TadaAkihiro en-aut-sei=Tada en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Okayama University kn-affil= affil-num=4 en-affil=Okayama Diagnostic Imaging Center kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= en-keyword=ovarian cancer kn-keyword=ovarian cancer en-keyword=BRCA1/2 kn-keyword=BRCA1/2 en-keyword=radiogenomics kn-keyword=radiogenomics en-keyword=machine learning kn-keyword=machine learning en-keyword=MRI kn-keyword=MRI END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=5 article-no= start-page=309 end-page=316 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dynamics of Serum Amyloid A Levels in the Blood, Brain and Liver in a Mouse Model of Focal Cerebral Ischemia en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study examined the dynamics of serum amyloid A (SAA) levels in the blood, brain, and liver over time using a mouse model of focal cerebral ischemia induced by occlusion of the middle cerebral artery (MCA) for 4 h followed by reperfusion. Blood SAA concentrations increased transiently after cerebral infarction, coinciding with changes in brain and liver SAA gene expression and protein levels. SAA concentrations in the brain, liver, and blood increased at similar time points after cerebral infarction, suggesting that SAA may serve as an important indicator of the associated pathological condition. en-copyright= kn-copyright= en-aut-name=EgashiraSaki en-aut-sei=Egashira en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=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=UshioSoichiro en-aut-sei=Ushio en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ManabeAkiko en-aut-sei=Manabe en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MasakiAyuko en-aut-sei=Masaki en-aut-mei=Ayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MukaiRie en-aut-sei=Mukai en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraYoshihiko en-aut-sei=Nakamura en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HosokawaMasato en-aut-sei=Hosokawa en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SathoTomomitsu en-aut-sei=Satho en-aut-mei=Tomomitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SanoKazunori en-aut-sei=Sano en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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 Oncology and Infectious Disease 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 Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=5 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=6 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=7 en-affil=Department of Microbiology Laboratory, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=8 en-affil=Department of Emergency and Critical Care Medicine, Fukuoka University Hospital kn-affil= affil-num=9 en-affil=Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=10 en-affil=Department of Microbiology Laboratory, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=11 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=12 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= en-keyword=stroke kn-keyword=stroke en-keyword=cerebral ischemia kn-keyword=cerebral ischemia en-keyword=serum amyloid A kn-keyword=serum amyloid A en-keyword=temporal dynamics kn-keyword=temporal dynamics END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=5 article-no= start-page=299 end-page=308 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognostic Value of Combined Preoperative CALLY and SII Assessment in Patients Undergoing Resection for Esophageal Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study evaluated the prognostic significance of the C-reactive protein?albumin?lymphocyte (CALLY) index and systemic immune-inflammation (SII) index in predicting postoperative outcomes in patients with esophageal squamous cell carcinoma (ESCC). A retrospective analysis was performed on clinical data from 102 patients with ESCC who underwent surgical resection at Western Theater General Hospital of China between January 2020 and July 2023. The associations between preoperative CALLY and SII indices and relapse-free survival (RFS) and overall survival (OS) were examined. Survival curves were generated using the Kaplan?Meier method, and prognostic factors were identified using Cox proportional hazards regression analysis. Patients with a high CALLY index had significantly longer RFS (HR=0.30, 95% CI: 0.13-0.71), and those with a low SII index also had significantly longer RFS (HR=2.23, 95% CI: 1.12-4.41). Similarly, patients with a high CALLY index had significantly longer OS (HR=0.27, 95% CI: 0.13-0.55), and those with a low SII index had significantly longer OS (HR=2.27, 95% CI: 1.09-4.71). When patients were stratified into four groups, the low-CALLY?high-SII group showed significantly shorter RFS than the high-CALLY?low-SII group (HR=0.26, 95% CI: 0.11-0.61; p=0.013), and OS was also significantly worse in the low-CALLY?high-SII group (HR=0.22, 95% CI: 0.09-0.54; p=0.016). Univariate Cox regression analysis identified both CALLY and SII as significant prognostic factors. In multivariate analysis, the CALLY index and N stage were independently associated with RFS, whereas only tumor size remained independently associated with OS. The combined assessment of preoperative CALLY and SII indices may be useful for prognostic stratification in patients with ESCC undergoing upfront surgical resection. It may help identify high-risk patient subgroups with distinct survival outcomes, thereby providing a potential rationale for stratifying postoperative surveillance and tailoring individualized adjuvant strategies, although validation in larger prospective cohorts is warranted. en-copyright= kn-copyright= en-aut-name=XuTao en-aut-sei=Xu en-aut-mei=Tao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZhengYing en-aut-sei=Zheng en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuangXuemei en-aut-sei=Huang en-aut-mei=Xuemei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LuoHong en-aut-sei=Luo en-aut-mei=Hong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Oncology, The General Hospital of Western Theater Command kn-affil= affil-num=2 en-affil=Department of Oncology, The General Hospital of Western Theater Command kn-affil= affil-num=3 en-affil=Department of Oncology, The General Hospital of Western Theater Command kn-affil= affil-num=4 en-affil=Department of Oncology, The General Hospital of Western Theater Command kn-affil= en-keyword=CALLY index kn-keyword=CALLY index en-keyword=SII index kn-keyword=SII index en-keyword=esophageal squamous cell carcinoma kn-keyword=esophageal squamous cell carcinoma en-keyword=prognosis kn-keyword=prognosis END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=5 article-no= start-page=289 end-page=298 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High Accuracy of Pelvic Tilt Measurement Using Three-Dimensional Planning Software: A Validation Study Using Dry Bone Models en-subtitle= kn-subtitle= en-abstract= kn-abstract=The “CR Alignment” function was recently introduced in ZedHip?, the hip joint module of ZedView?, to evaluate pelvic tilt in non-supine positions via two-dimensional (2D)?3D matching using radiographs. However, its ccuracy has not been validated. This study therefore evaluated the accuracy of pelvic tilt measurements using the CR Alignment function in dry pelvic bone specimens. Two cadaveric pelvic bone models were placed in nine orientations (anterior/posterior tilt and left/right rotation). Both radiographic and CT images were acquired in each position. In Study 1, pelvic tilt measured directly from CT images was defined as the “true value.” Three observers used the CR Alignment function to calculate pelvic tilt on radiographs, and measurement errors were determined relative to the true values. In Study 2, measurement errors were compared between matched (same position) and mismatched (different position) imaging. In Study 1, the mean measurement error was 1.28±0.64°. Intra- and interobserver intraclass correlation coefficients were 0.996-0.998 and 0.997, respectively. In Study 2, the mean errors were 1.20±0.88° (matched) and 1.32±1.03° (mismatched). This software exhibited high accuracy and reproducibility in 2D?3D matching of pelvic tilt, with lower variability under matched acquisition, demonstrating its utility for pre- and postoperative assessment in joint arthroplasty. en-copyright= kn-copyright= en-aut-name=KomutaYuki en-aut-sei=Komuta en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ImaiNorio en-aut-sei=Imai en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HommaDaisuke en-aut-sei=Homma en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FunayamaKazuhisa en-aut-sei=Funayama en-aut-mei=Kazuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HiranoYuki en-aut-sei=Hirano en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HorigomeYoji en-aut-sei=Horigome en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MinatoIzumi en-aut-sei=Minato en-aut-mei=Izumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawashimaHiroyuki en-aut-sei=Kawashima en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=2 en-affil=Division of Comprehensive Musculoskeletal Medicine, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=3 en-affil=Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=4 en-affil=Division of Legal Medicine, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=5 en-affil=Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=6 en-affil=Division of Comprehensive Musculoskeletal Medicine, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Niigata Rinko Hospital kn-affil= affil-num=8 en-affil=Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= en-keyword=total hip arthroplasty kn-keyword=total hip arthroplasty en-keyword=pelvic tilt kn-keyword=pelvic tilt en-keyword=three-dimensional planning software kn-keyword=three-dimensional planning software en-keyword=two-dimensional and threedimensional matching kn-keyword=two-dimensional and threedimensional matching en-keyword=radiographic analysis kn-keyword=radiographic analysis END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=5 article-no= start-page=279 end-page=288 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Diabetes Mellitus as a Risk Factor for Severe COVID-19 and Pneumonia: A Comparison Between the Pre-Omicron and Omicron-Dominant Periods in Okayama City, Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Diabetes mellitus is a well-established risk factor for severe COVID-19; however, few studies have examined this association during the Omicron-dominant period. We conducted a population-based study using surveillance data from the Okayama City Public Health Center in Japan to compare the risk of severe COVID-19 and pneumonia among patients with diabetes mellitus between the pre-Omicron (March 2020?December 2021) and Omicron-dominant (January?September 2022) periods. Among 98,905 COVID-19 patients aged 10 years or older, we calculated adjusted odds ratios (aORs) controlling for age, sex, smoking status, comorbidities, obesity, and the number of COVID-19 vaccine doses received. In the pre-Omicron period, diabetes mellitus was significantly associated with severe COVID-19 (aOR: 1.36; 95% CI: 1.03-1.78), and this association persisted in the Omicron-dominant period (aOR: 1.54; 95% CI: 1.10-2.17). Similar findings were observed for pneumonia. The association was more pronounced among patients aged 40-69 years than among those aged 70 years or older. These findings suggest that diabetes mellitus remains an important risk factor for severe COVID-19 even during the Omicron-dominant period, highlighting the need for continued clinical vigilance and early intervention in patients with diabetes mellitus. en-copyright= kn-copyright= en-aut-name=MiyamotoSatoshi en-aut-sei=Miyamoto en-aut-mei=Satoshi 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=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=TakaoSoshi en-aut-sei=Takao en-aut-mei=Soshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= affil-num=1 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Center for Innovative Clinical Medicine, Medical Development Field, Okayama University kn-affil= affil-num=4 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=diabetes mellitus kn-keyword=diabetes mellitus en-keyword=Omicron variant kn-keyword=Omicron variant en-keyword=severity kn-keyword=severity en-keyword=population-based study kn-keyword=population-based study END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=5 article-no= start-page=271 end-page=277 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Artificial Intelligence-Assisted Peroral Cholangioscopy for the Diagnosis and Management of Biliary Strictures: Current Evidence and Future Directions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Peroral cholangioscopy (POCS) enables direct intraductal visualization and targeted biopsies for indeterminate biliary strictures. However, its diagnostic performance remains operator-dependent and is limited by sampling error. As artificial intelligence (AI) has rapidly advanced in gastrointestinal endoscopy, AI-assisted cholangioscopy has progressed from proof-of-concept image classification to multicenter validation, feature detection, and real-time application. Recent studies using digital single-operator cholangioscopy have reported diagnostic accuracy comparable to that of experts in differentiating malignant from benign strictures, and feature-based approaches can automatically detect tumor vessels and other key visual characteristics. Beyond classification, generative models may enhance mucosal and margin visualization through virtual chromoendoscopy, potentially improving lesion-margin assessment. Furthermore, new models compatible with multiple systems are emerging to address device heterogeneity, which is a key barrier to routine practice. This review summarizes the current evidence on AI-assisted POCS, discusses practical considerations for clinical translation, and highlights future directions, including real-time integration and multimodal decision support. en-copyright= kn-copyright= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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= en-keyword=peroral cholangioscopy kn-keyword=peroral cholangioscopy en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=biliary stricture kn-keyword=biliary stricture en-keyword=deep learning kn-keyword=deep learning en-keyword=virtual chromoendoscopy kn-keyword=virtual chromoendoscopy END start-ver=1.4 cd-journal=joma no-vol=85 cd-vols= no-issue=9 article-no= start-page=2608 end-page=2618 dt-received= dt-revised= dt-accepted= dt-pub-year=2002 dt-pub=200209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A New Route for Preparation of 5-Deoxy-5-(hydroxyphosphinyl)- D-mannopyranose and -L-gulopyranose Derivatives en-subtitle= kn-subtitle= en-abstract= kn-abstract=Starting from methyl 2,3-O-isopropylidene-α-D-mannofuranoside (5), methyl 6-O-benzyl-2,3-O-isopropylidene-α-D-lyxo-hexofuranosid-5-ulose (12) was prepared in three steps. The addition reaction of dimethyl phosphonate to 12, followed by deoxygenation of 5-OH group, provided the 5-deoxy-5-dimethoxyphosphinyl-α-D-mannofuranoside derivative 15a and the β-L-gulofuranoside isomer 15b. Reduction of 15a and 15b with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by the action of HCl and then H2O2, afforded the D-mannopyranose (17) and L-gulopyranose analog 21, each having a phosphinyl group in the hemiacetal ring. These were converted to the corresponding 1,2,3,4,6-penta-O-acetyl-5-methoxyphosphinyl derivatives 19 and 23, respectively, structures and conformations (4C1 or 1C4, resp.) of which were established by 1H-NMR spectroscopy. 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=YamamotoHiroshi en-aut-sei=Yamamoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Center of Instrumental Analysis, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=6 article-no= start-page=48 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20261015 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A simple proof for the existence of V-form fronts in reaction?diffusion equations en-subtitle= kn-subtitle= en-abstract= kn-abstract=This paper studies V-form traveling fronts to a bistable reaction?diffusion equation. V-form traveling fronts have been studied so far for many reaction?diffusion equations. The proof of its existence is often based on the multi-scale method. In this paper we present a new simple proof for the existence of V-form traveling fronts based on estimates by inscribed balls. en-copyright= kn-copyright= en-aut-name=NagashimaSatomu en-aut-sei=Nagashima en-aut-mei=Satomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TaniguchiMasaharu en-aut-sei=Taniguchi en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaylorGeorge en-aut-sei=Taylor en-aut-mei=George kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, Advanced Research Field, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Traveling front kn-keyword=Traveling front en-keyword=V-form kn-keyword=V-form en-keyword=Reaction?diffusion equation kn-keyword=Reaction?diffusion equation END start-ver=1.4 cd-journal=joma no-vol=1 cd-vols= no-issue=3 article-no= start-page=202615 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Advances and Future Perspectives of Targeted Mutagenesis in Barley en-subtitle= kn-subtitle= en-abstract= kn-abstract=Targeted mutagenesis technologies, commonly referred to as “genome editing”, have rapidly become transformative tools in crop breeding. Modern crop production faces mounting challenges such as climate change, emerging diseases, and shifting quality demands, creating an urgent need for breeding approaches that enable more precise genetic improvement within shorter timeframes. Targeted mutagenesis capable of introducing mutations accurately and efficiently began with the development of meganucleases and subsequently evolved through ZFNs, TALENs, and CRISPR/Cas systems. Recent technological advances, including multiplex editing and DNA-free genome editing, have made direct modification of elite cultivars increasingly feasible, helping to overcome long-standing barriers associated with genotype dependency and the complexity of polyploid genomes. Targeted mutagenesis has now been applied to a wide range of breeding targets, including disease resistance, tolerance to abiotic stresses, yield-related traits, and quality traits. Moreover, machine learning and AI are beginning to support target selection and phenotype prediction, ushering in an era in which genome editing can be integrated into breeding programs more rationally and efficiently. These scientific developments coincide with regulatory shifts in many countries toward easing restrictions on new genomic techniques (NGTs), particularly by treating SDN-1 genome-edited crops equivalently to those produced through conventional breeding. Such changes are expected to accelerate field trials, commercialization, and international collaboration. Nevertheless, several challenges remain, including bottlenecks in transformation efficiency, off-target assessment, the control of complex traits, societal acceptance, and unresolved regulatory details. Even so, genome editing is poised to become a central technology in next-generation cereal breeding, enabling the development of cultivars with greater resilience, productivity, and adaptability to diverse industrial needs. en-copyright= kn-copyright= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=CRISPR/Cas9 kn-keyword=CRISPR/Cas9 en-keyword=genome editing kn-keyword=genome editing en-keyword=Hordeum vulgare kn-keyword=Hordeum vulgare en-keyword=plant breeding kn-keyword=plant breeding en-keyword=transformation amenability kn-keyword=transformation amenability END start-ver=1.4 cd-journal=joma no-vol=51 cd-vols= no-issue=10 article-no= start-page=533 end-page=547 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=Integration of QSAR modeling and in vitro validation for identification of food-derived Nrf2 activators against arsenic-induced toxicity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Arsenic exposure is a major public health concern due to its toxicity and carcinogenicity, largely mediated by oxidative stress, and activation of the Nrf2 signaling pathway is considered a promising strategy to mitigate such damage. In this study, a quantitative structure?activity relationship (QSAR) model was developed to identify potential Nrf2 activators from food-derived compounds. Machine learning algorithms, including Random Forest (RF), Support Vector Machine (SVM), Linear Discriminant Analysis (LDA), and a stacking model, were developed and optimized. The optimized RF, SVM, and LDA models were subsequently integrated into a stacking framework, which was selected as the final predictive model for virtual screening based on its robust and balanced predictive performance. The stacking model achieved the highest accuracy during five-fold cross-validation (0.77) and demonstrated competitive performance on the independent test set (0.742 ± 0.040), with balanced precision, sensitivity, and F-measure. Consequently, the stacking model was selected as the final model for virtual screening. A total of 70,926 compounds retrieved from a food-derived database were filtered based on physicochemical criteria, and QSAR-based virtual screening predicted 920 compounds as potential activators of the Nrf2 signaling pathway, from which 5,7-Dimethylchrysin (FooDB ID: FDB015537) and Demethylvestitol (FooDB ID: FDB012218) were selected for experimental validation. In vitro assays using HepG2 cells demonstrated that 5,7-Dimethylchrysin significantly enhanced cell viability against sodium arsenite (150 μM)-induced cytotoxicity, with an effective concentration (EC50) of 0.54 μM, whereas Demethylvestitol exhibited only limited protective effects. Furthermore, luciferase reporter assays confirmed that 5,7-Dimethylchrysin activated antioxidant response element (ARE)-driven transcription in a concentration-dependent manner, producing a 1.5 to 2.4-fold increase at concentrations ranging from 0.78 to 6.25 μM. Overall, these findings highlight the effectiveness of integrating QSAR modeling with experimental validation to identify food-derived compounds with protective potential against arsenic-induced toxicity, with 5,7-Dimethylchrysin emerging as a promising candidate for further investigation. en-copyright= kn-copyright= en-aut-name=HuongNgo Thanh en-aut-sei=Huong en-aut-mei=Ngo Thanh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KodamaSusumu en-aut-sei=Kodama en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnoAtsushi en-aut-sei=Ono en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Laboratory of Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Laboratory of Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Laboratory of Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Arsenic toxicity kn-keyword=Arsenic toxicity en-keyword=Nrf2 activator kn-keyword=Nrf2 activator en-keyword=QSAR modeling kn-keyword=QSAR modeling en-keyword=Food-derived compounds kn-keyword=Food-derived compounds en-keyword=In vitro kn-keyword=In vitro END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=20 article-no= start-page=3393 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20261012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cross-Cultural Adaptation and Initial Psychometric Evaluation of the Japanese Version of the Chronic Kidney Disease Self-Efficacy Scale (CKDSE-J) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Self-efficacy is an important determinant of self-care among adults with chronic kidney disease (CKD). The Chronic Kidney Disease Self-Efficacy Scale (CKD-SE) is a disease-specific measure, but its use has not been reported in Japan. This study translated and culturally adapted the CKD-SE into Japanese and conducted an initial psychometric evaluation. Methods: A cross-sectional survey was conducted among Japanese adults with CKD stages G3a?G5 not receiving dialysis. Structural validity and internal consistency were evaluated in 227 participants, and construct validity was evaluated in 222. Structural validity was examined using confirmatory factor analysis (CFA) and exploratory structural equation modeling (ESEM). Results: The original 25-item four-factor CFA showed a poor fit, and ESEM yielded an improper solution involving Item 19. Sequential evaluation resulted in a 23-item structure. The 23-item CFA showed mixed fit, whereas Target ESEM showed improved overall fit (CFI = 0.935, TLI = 0.902, RMSEA = 0.060, SRMR = 0.033). However, several autonomy items showed weak target loadings and cross-loadings. Proposed subscale scores correlated positively with self-care behavior (r = 0.27?0.46), and McDonald’s omega ranged from 0.84 to 0.90. Conclusions: The 23-item CKDSE-J showed improved overall model fit under Target ESEM, but the structural definition of autonomy remained uncertain. Because the structure was refined and evaluated in the same sample, independent replication and further psychometric evaluation are needed. en-copyright= kn-copyright= en-aut-name=GengTingting en-aut-sei=Geng en-aut-mei=Tingting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KajiwaraYuki en-aut-sei=Kajiwara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimotoMichiko en-aut-sei=Morimoto en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Doctor’s Program, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Health Sciences, Okayama University kn-affil= en-keyword=chronic kidney disease kn-keyword=chronic kidney disease en-keyword=self-efficacy kn-keyword=self-efficacy en-keyword=self-care kn-keyword=self-care en-keyword=cultural adaptation kn-keyword=cultural adaptation en-keyword=psychometric evaluation kn-keyword=psychometric evaluation en-keyword=exploratory structural equation modeling kn-keyword=exploratory structural equation modeling END start-ver=1.4 cd-journal=joma no-vol=340 cd-vols= no-issue=1 article-no= start-page=31 end-page=37 dt-received= dt-revised= dt-accepted= dt-pub-year=2005 dt-pub=20050117 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis and structural analysis of 6-deoxy-6-hydroxyphosphinyl-d-fructopyranose derivatives en-subtitle= kn-subtitle= en-abstract= kn-abstract=3,4-Di-O-benzyl-6-deoxy-6-diethoxyphosphinyl-1,2-O-isopropylidene-β-d-fructofuranose (13) was prepared from the known 1,2-O-isopropylidene-6-O-tosyl-β-d-fructofuranose in five steps. Reduction of 13 with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by the action of hydrochloric acid and then hydrogen peroxide, afforded the 6-deoxy-6-hydroxyphosphinyl-d-fructopyranose derivative. This was converted into the 1,2,3,4,5-penta-O-acetyl-6-deoxy-6-methoxyphosphinyl-d-fructopyranoses, whose structure and conformation were established by 1H NMR spectroscopy. 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=ImaiKumiko en-aut-sei=Imai en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Prikhod’koYurij V. en-aut-sei=Prikhod’ko en-aut-mei=Yurij V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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= affil-num=4 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= en-keyword=Phospho sugar kn-keyword=Phospho sugar en-keyword=6-Deoxy-6-phosphinyl-d-fructopyranose kn-keyword=6-Deoxy-6-phosphinyl-d-fructopyranose en-keyword=Hydroxyphosphinyl group kn-keyword=Hydroxyphosphinyl group en-keyword=Acetyl migration kn-keyword=Acetyl migration en-keyword=Conformational analysis kn-keyword=Conformational analysis END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=30805 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cinnamyl alcohol dehydrogenase (CAD) underlies the orange lemma trait and lignin reduction in barley en-subtitle= kn-subtitle= en-abstract= kn-abstract=Barley (Hordeum vulgare L.) is one of the world’s major cereal crops and is widely used for feed, brewing, and food. Reducing lignin content in barley grain and straw is beneficial for improving forage digestibility and enhancing the efficiency of bioethanol production. The orange lemma mutation?characterized by orange pigmentation of husks and nodes?has long been associated with altered lignin metabolism; however, its genetic basis has remained unclear. We show that Cinnamyl Alcohol Dehydrogenase (CAD) is the causal gene underlying the orange lemma phenotype in barley. Genetic mapping using a ‘Haruna Nijo’?×?‘L053’ F? population and the Barley 50 K SNP array defined a candidate region on chromosome 6H containing the CAD gene. Sequence analysis revealed that all orange lemma mutants, including both naturally occurring and EMS-induced lines, carried nucleotide changes in the CAD gene, resulting in amino acid substitutions or premature stop codons. Furthermore, CRISPR/Cas9-mediated knockout of CAD in the cultivar ‘Golden Promise’ reproduced the orange lemma phenotype, providing functional validation. The knockout plants also showed significantly lower lignin content than wild-type plants. These findings resolve a long-standing question regarding the genetic basis of the orange lemma trait and demonstrate that disruption of CAD alters lignin accumulation in barley. This work provides a valuable genetic resource for breeding barley cultivars with improved biomass utilization for feed and bioenergy applications. en-copyright= kn-copyright= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoritaMaho en-aut-sei=Morita en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamajiNami en-aut-sei=Yamaji en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KakoRinka en-aut-sei=Kako en-aut-mei=Rinka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UshijimaTomokazu en-aut-sei=Ushijima en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=Graduate School of Agricultural Science, Setsunan University kn-affil= affil-num=5 en-affil=Graduate School of Agricultural Science, Setsunan University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Cinnamyl Alcohol Dehydrogenase (CAD) kn-keyword=Cinnamyl Alcohol Dehydrogenase (CAD) en-keyword=Barley kn-keyword=Barley en-keyword=Orange lemma kn-keyword=Orange lemma en-keyword=Lignin kn-keyword=Lignin en-keyword=Genome editing kn-keyword=Genome editing END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=3 article-no= start-page=1525 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=Bioinformatic Prediction of Activation States in Molecular Network Pathways of Eukaryotic Initiation Factor 2 (EIF2) Signaling and Coronavirus Pathogenesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Eukaryotic initiation factor 2 (EIF2) signaling plays a crucial role in regulating mRNA translation and initiating eukaryotic protein synthesis. Computational molecular network pathway analysis of the canonical pathways of the coronaviral infection revealed that EIF2 signaling is inactivated when the coronavirus pathogenesis pathway is activated and vice versa. Our computational analyses indicated that the coronavirus pathogenesis pathway and EIF2 signaling had inverse activation states. Computational investigation of upstream or downstream microRNA (miRNA) revealed that EIF2 signaling directly interacted with miRNAs, including let-7, miR-1292-3p (miRNAs with the seed CGCGCCC), miR-15, miR-34, miR-378, miR-493, miR-497, miR-7, miR-8, and MIRLET7. A total of 36 nodes, including 8 molecules (ATF4, BCL2, CCND1, DDIT3, EIF2A, EIF2AK3, EIF4E, and ERK1/2), 1 complex (the ribosomal 40s subunit), and 1 function (apoptosis) in the coronavirus pathogenesis pathway, overlapped with EIF2 signaling. Alterations in EIF2 signaling may play a role in the pathogenesis of coronavirus. en-copyright= kn-copyright= en-aut-name=TanabeShihori en-aut-sei=Tanabe en-aut-mei=Shihori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=QuaderSabina en-aut-sei=Quader en-aut-mei=Sabina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnoRyuichi en-aut-sei=Ono en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaHiroyoshi Y. en-aut-sei=Tanaka en-aut-mei=Hiroyoshi Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CabralHoracio en-aut-sei=Cabral en-aut-mei=Horacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=2 en-affil=Innovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion kn-affil= affil-num=3 en-affil=Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=4 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Bioengineering, Graduate School of Engineering, The University of Tokyo kn-affil= en-keyword=coronavirus kn-keyword=coronavirus en-keyword=EIF2 signaling kn-keyword=EIF2 signaling en-keyword=microRNA kn-keyword=microRNA en-keyword=molecular pathway kn-keyword=molecular pathway en-keyword=network activation kn-keyword=network activation 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=20261005 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Experimental evolution of female mating responses to infertile males in Tribolium castaneum en-subtitle= kn-subtitle= en-abstract= kn-abstract=In many animal populations, infertile males?those unable to reproduce?are commonly present. If females mate exclusively with such males, they fail to produce offspring. How, then, do females deal with this situation? Distinguishing infertile from fertile males both before and after copulation is difficult for females. Here, we tested the hypothesis of bet-hedging polyandry, in which females mitigate the risk of reproductive failure by mating with multiple males, using experimental evolution in the red flour beetle (Tribolium castaneum). Females were cohabited with males artificially sterilized by sublethal radiation and with untreated males at a 1:1 ratio (sterile:untreated). After more than 15 generations, females from the treatment strains did not avoid mating with infertile males, leading to reduced reproductive success. However, compared with the control strains, females from the treated strains tended to mate with a greater number of males. The results raise the possibility that increased polyandry (mating with multiple males) may evolve rather than relying on pre- or post-copulatory discrimination to mitigate the risk posed by infertile males. Bet-hedging is a strategy that spreads or minimizes risk under uncertainty, and these results are consistent with the hypothesis that polyandry can function as a bet-hedging strategy against uncertain male fertility. en-copyright= kn-copyright= en-aut-name=FujiiYui en-aut-sei=Fujii en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsanoYui en-aut-sei=Asano en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KoriKenta en-aut-sei=Kori en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumuraKentarou en-aut-sei=Matsumura en-aut-mei=Kentarou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YasuiYukio en-aut-sei=Yasui en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HimuroChihiro en-aut-sei=Himuro en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamotoYutaka en-aut-sei=Nakamoto en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SokeiYoshitaka en-aut-sei=Sokei en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Faculty of Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Arts and Sciences, The University of Tokyo kn-affil= affil-num=5 en-affil=Faculty of Agriculture, Kagawa University kn-affil= affil-num=6 en-affil=Okinawa Prefectural Plant Protection Center kn-affil= affil-num=7 en-affil=Okinawa Prefectural Plant Protection Center kn-affil= affil-num=8 en-affil=Okinawa Prefectural Plant Protection Center kn-affil= affil-num=9 en-affil=Faculty of Environmental, Natural Science and Technology, Okayama University kn-affil= en-keyword=Beetle kn-keyword=Beetle en-keyword=Bet-hedging kn-keyword=Bet-hedging en-keyword=Copulation kn-keyword=Copulation en-keyword=Matingbehavior kn-keyword=Matingbehavior en-keyword=Reproductive failure kn-keyword=Reproductive failure END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=11 article-no= start-page=132 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20261007 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=No evidence for differential allocation or sex ratio adjustment in response to male attractiveness in the broad-horned flour beetle en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sexual selection theory predicts that females can enhance the benefits of mate choice by increasing reproductive investment (differential allocation) or by biasing offspring sex ratios toward sons (sex ratio adjustment) when mating with attractive males. Clear empirical support for these hypotheses has been documented in many vertebrate taxa, whereas relatively few studies have tested them in invertebrates. Here, we investigated whether females adjust reproductive investment and offspring sex ratio in response to male attractiveness in the beetle Gnatocerus cornutus. We assessed male attractiveness using copulation latency and examined its associations with female lifetime reproductive success, egg size, and offspring sex ratio under single-mating conditions. Our results, however, provide no support for either the differential allocation or sex ratio adjustment hypotheses: females did not alter reproductive investment or offspring sex ratio according to mate quality. In this species, male sexual phenotypes are strongly influenced by environmental conditions. Such phenotype?genotype mismatches may reduce the reliability of male traits as indicators of genetic quality and increase the likelihood of assessment errors by females. This may explain the absence of maternal allocation in relation to mate attractiveness in G. cornutus. Instead, previous work on this beetle indicates that females can secure genetic benefits by remating with more attractive males and biasing fertilization toward their sperm. Our findings therefore suggest that postcopulatory mechanisms, rather than differential maternal allocation, provide a more effective route for females to secure the benefits of mate choice in G. cornutus. en-copyright= kn-copyright= en-aut-name=OkadaKensuke en-aut-sei=Okada en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KiyoseKatsuya en-aut-sei=Kiyose en-aut-mei=Katsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatsukiMasako en-aut-sei=Katsuki en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Seibukasei Co., Ltd kn-affil= affil-num=3 en-affil=Graduate School of Bioagricultural Sciences, Nagoya University kn-affil= en-keyword=Fisherian process kn-keyword=Fisherian process en-keyword=good genes kn-keyword=good genes en-keyword=horned beetle kn-keyword=horned beetle en-keyword=life-history evolution kn-keyword=life-history evolution en-keyword=sexual selection kn-keyword=sexual selection END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=1 article-no= start-page=742 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260914 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rapid fluvial response to meter-scale coseismic coastal uplift during the 2024 Noto Peninsula earthquake en-subtitle= kn-subtitle= en-abstract= kn-abstract=The response of river profiles to relative base-level change is a key topic in earth surface processes, but observations capturing these changes on unconsolidated deposits at a 1?10 years timescales are scarce. We monitored geomorphic changes at the Hakka River mouth after the 3.5-meter base-level fall caused by coseismic uplift of the 2024 Noto Peninsula earthquake, Japan. Utilizing uncrewed aerial vehicle surveys, we documented a maximum vertical riverbed lowering of 2?m and knickpoint upstream migration of 770-m within the first-year post-earthquake, primarily triggered by erosion during major floods that followed the earthquake. Our findings demonstrate that fluvial terraces can develop within a year or less, following co-seismic coastal uplift. However, the river has not yet reached a renewed graded stage because riverbed armoring resulting from sediment sorting during incision currently inhibits further incision. We suggest that the abandonment of alluvial plains and lowering and widening of the riverbed in the lower 10-km segment will continue over the next decade. en-copyright= kn-copyright= en-aut-name=TakahashiTakayuki en-aut-sei=Takahashi en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OguraTakuro en-aut-sei=Ogura en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IizukaKotaro en-aut-sei=Iizuka en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwasaYoshiya en-aut-sei=Iwasa en-aut-mei=Yoshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HayakawaYuichi S. en-aut-sei=Hayakawa en-aut-mei=Yuichi S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AokiTatsuto en-aut-sei=Aoki en-aut-mei=Tatsuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MattaNobuhisa en-aut-sei=Matta en-aut-mei=Nobuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=International Research Institute of Disaster Science, Tohoku University kn-affil= affil-num=2 en-affil=Graduate School of Social Sciences, Hitotsubashi University kn-affil= affil-num=3 en-affil=Center for Spatial Information Science, The University of Tokyo kn-affil= affil-num=4 en-affil=Faculty of Education, University of Teacher Education Fukuoka kn-affil= affil-num=5 en-affil=Center for Spatial Information Science, The University of Tokyo kn-affil= affil-num=6 en-affil=Institute of Human and Social Sciences, Kanazawa University kn-affil= affil-num=7 en-affil=Graduate School of Education, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=11689307 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=Tourism Demand Forecasting Using Machine Learning with Cross-Model Feature Ranking en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study proposes a machine learning (ML) framework for forecasting tourist visits to a destination, leveraging feature ranking consistency across heterogeneous models. The proposed framework uses a unified stepwise feature selection pipeline to systematically determine a subset of given features that reduces prediction error of an ML model. The transferability of feature rankings is demonstrated through experiments using ML models including Random Forest, XGBoost, LightGBM, and Support Vector Regression (SVR), and a dataset related to tourist visits to West Sumatra, Indonesia. Experimental results show that i) SVR using top four features in the feature ranking based on SHAP achieves the highest accuracy and ii) application of the feature ranking based on XGBoost improves performance stability across other models, reducing error fluctuations. These findings reveal that an optimized feature subset combined with cross-model ranking transfer can outperform more complex ensembles, highlighting the importance of ranking robustness in tourism forecasting. The proposed framework provides a methodological foundation for building interpretable and dataefficient decision support systems for tourism management and policy planning. en-copyright= kn-copyright= en-aut-name=HendraYomei en-aut-sei=Hendra en-aut-mei=Yomei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MigitaTsuyoshi en-aut-sei=Migita en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiNorikazu en-aut-sei=Takahashi en-aut-mei=Norikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Okayama University kn-affil= affil-num=3 en-affil=Okayama University kn-affil= en-keyword=tourism forecasting kn-keyword=tourism forecasting en-keyword=machine learning kn-keyword=machine learning en-keyword=support vector regression kn-keyword=support vector regression en-keyword=XGBoost kn-keyword=XGBoost en-keyword=feature ranking kn-keyword=feature ranking END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=1 end-page=6 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=A Novel Iterative Method for Principal Component Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Principal Component Analysis (PCA) is a statistical method used for identifying key patterns from a given dataset and reducing its dimensions, while retaining most of the original information. The power method, which is one of the most well-known algorithms for PCA, is simple and easy to implement. However it obtains the specified number of principal components one by one. In this paper, we propose a novel iterative method for PCA, which is expressed as a system of nonlinear difference equations. Unlike the power method, the proposed method can obtain the specified number of principal components in parallel. We also show results of numerical experiments and theoretical analysis to verify the validity of the proposed method. en-copyright= kn-copyright= en-aut-name=CaoQiuyun en-aut-sei=Cao en-aut-mei=Qiuyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HattoriKotaro en-aut-sei=Hattori en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MigitaTsuyoshi en-aut-sei=Migita en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiNorikazu en-aut-sei=Takahashi en-aut-mei=Norikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Okayama University kn-affil= affil-num=3 en-affil=Okayama University kn-affil= affil-num=4 en-affil=Okayama University kn-affil= en-keyword=principal component analysis kn-keyword=principal component analysis en-keyword=power method kn-keyword=power method en-keyword=discrete-time nonlinear system kn-keyword=discrete-time nonlinear system en-keyword=equilibrium point kn-keyword=equilibrium point en-keyword=stability kn-keyword=stability END start-ver=1.4 cd-journal=joma no-vol=526 cd-vols= no-issue= article-no= start-page=150819 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Flavor encapsulation capacities of amphiphilic polyvinylpyrrolidone as a carrier for amorphous solid dispersions en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigates the characteristics of amorphous solid dispersions (ASDs) formed using an amphiphilic carrier polymer, focusing on the effects of source solution conditions on flavor retention. Cinnamaldehyde and polyvinylpyrrolidone (PVP) were dissolved as flavor and carrier components in methanol or ethanol under different conditions and subsequently spray-dried into fine powders. The amount of cinnamaldehyde retained in the spray-dried ASDs was quantified to assess the impact of solution conditions. The results indicate that cinnamaldehyde molecules were physically entrapped within the entangled PVP chains during the spray-drying process. The flavor encapsulation capacity of PVP reached a maximum of approximately 4 mmol/g-PVP under specific conditions. This maximum capacity implies that each cinnamaldehyde molecule is associated with approximately two PVP monomer units, which is higher than those reported for selected cyclodextrin-based systems in comparable contexts of cinnamaldehyde encapsulation. Additionally, the dissipation of cinnamaldehyde from the ASD samples during storage under vacuum was examined. en-copyright= kn-copyright= en-aut-name=SatoHaruna en-aut-sei=Sato en-aut-mei=Haruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HondaNao en-aut-sei=Honda en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasegawaTakato en-aut-sei=Hasegawa en-aut-mei=Takato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AragaChika en-aut-sei=Araga en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImanakaHiroyuki en-aut-sei=Imanaka en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshidaNaoyuki en-aut-sei=Ishida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ImamuraKoreyoshi en-aut-sei=Imamura en-aut-mei=Koreyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Department of Chemical Engineering and Material Sciences, Faculty of Science and Engineering, Doshisha University kn-affil= affil-num=7 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Flavor encapsulation kn-keyword=Flavor encapsulation en-keyword=Polyvinylpyrrolidone kn-keyword=Polyvinylpyrrolidone en-keyword=Spray-drying kn-keyword=Spray-drying en-keyword=Encapsulation capacity kn-keyword=Encapsulation capacity en-keyword=Overlap concentration kn-keyword=Overlap concentration en-keyword=Encapsulation pocket kn-keyword=Encapsulation pocket END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=1 article-no= start-page=37 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20261001 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Delta morphology reveals timings of early ocean regression and hydrologic shift on ancient Mars en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mars’ ancient hydrologic history remains a subject of debate, with competing interpretations suggesting either a large ocean or scattered lacustrine environments. Here, we show that delta morphology on Mars records a shift between these hydrologic regimes. Through controlled tank experiments, we identify two distinct delta types: “lobe-extruding deltas” formed during water-level falls and “stepped fan-deltas” formed during rising water levels. The lobe-extruding deltas occur near proposed paleo-coastlines and are dated to ~3.8?3.2 Ga, consistent with the existence of a Late Noachian?Hesperian ocean and its subsequent regression in the Late Hesperian. In contrast, stepped fan-deltas are found at a wider range of elevations and exhibit significantly younger ages (~2.1?0.1 Ga), suggesting episodic, localized lake formation during the Amazonian. Our findings constrain the timing of the planetary-scale transition from a global hydrosphere to localized aqueous environments and refine the understanding of Mars’ paleoclimate evolution and potential habitability. en-copyright= kn-copyright= en-aut-name=KitoRen en-aut-sei=Kito en-aut-mei=Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HasegawaHitoshi en-aut-sei=Hasegawa en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RujTrishit en-aut-sei=Ruj en-aut-mei=Trishit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MutoTetsuji en-aut-sei=Muto en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OriGian Gabriele en-aut-sei=Ori en-aut-mei=Gian Gabriele kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KomatsuGoro en-aut-sei=Komatsu en-aut-mei=Goro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Science and Technology, Kochi University kn-affil= affil-num=3 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=4 en-affil=Department of Environmental Science, Nagasaki University kn-affil= affil-num=5 en-affil=International Research School of Planetary Sciences, Universit? d’Annunzio kn-affil= affil-num=6 en-affil=International Research School of Planetary Sciences, Universit? d’Annunzio kn-affil= END start-ver=1.4 cd-journal=joma no-vol=248 cd-vols= no-issue= article-no= start-page=117443 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202611 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Molecular characteristics and clinical outcomes of ERBB2-activating mutation-positive non-small cell lung cancer: A Japanese nationwide real-world cohort en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Erb-b2 receptor tyrosine kinase 2 (ERBB2)-activating mutations are well-documented oncogenic drivers in non-small cell lung cancer (NSCLC), occurring in approximately 1?4% of cases. These alterations include a heterogeneous spectrum of variant subtypes; however, the clinicogenomic characteristics and clinical significance of the individual variants have yet to be elucidated.
Methods: We searched the nationwide Center for Cancer Genomics and Advanced Therapeutics database, which integrates comprehensive genome profiling data generated in routine clinical practice across Japan, to investigate the molecular landscape and clinical outcomes of patients with ERBB2-mutated NSCLC.
Results: A total of 319 patients with ERBB2-activating mutations were included in this retrospective analysis. Although 74% of the patients harbored canonical tyrosine kinase domain (TKD) in-frame insertions, 26% carried noncanonical variants, including TKD missense (8%), transmembrane/juxtamembrane domain (10%), and extracellular domain (ECD) mutations (8%). Co-occurring oncogenic driver alterations were identified in only 18 cases (5.6%) and were largely restricted to noncanonical variants, whereas no co-occurring driver alterations were detected among patients with TKD in-frame mutations. Noncanonical variants?TKD missense and ECD mutations in particular?were associated with an increased tumor mutational burden. Among 288 patients with available survival data, 78 (27%) received trastuzumab deruxtecan (T-DXd) during their clinical course. After excluding patients who had started treatment with T-DXd before undergoing comprehensive genome profiling testing, time-dependent T-DXd exposure was associated with a reduced risk of death (adjusted hazard ratio, 0.63; 95% confidence interval, 0.39?1.01; P?=?0.057).
Conclusions: ERBB2-mutated NSCLC exhibited substantial molecular heterogeneity, with canonical TKD in-frame insertions characterized by a low frequency of co-occurring oncogenic driver alterations. Among patients harboring ERBB2-activating mutations, exposure to T-DXd was associated with improved overall survival. en-copyright= kn-copyright= en-aut-name=YamashitaMasahiro en-aut-sei=Yamashita en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=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=MoritaAyako en-aut-sei=Morita en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaraNaofumi en-aut-sei=Hara en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakadaKenji en-aut-sei=Takada en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= en-keyword=ERBB2 mutation kn-keyword=ERBB2 mutation en-keyword=Variant subtype kn-keyword=Variant subtype en-keyword=Comprehensive genomic profiling kn-keyword=Comprehensive genomic profiling en-keyword=Trastuzumab-deruxtecan kn-keyword=Trastuzumab-deruxtecan en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=17 article-no= start-page=3880 end-page=3890 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260526 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sequential Immune Activation of Effector T Cells as Biomarkers of Response to Durvalumab in Patients with Locally Advanced NSCLC en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: Durvalumab therapy following concurrent chemoradiotherapy (cCRT) improves progression-free survival (PFS) in patients with unresectable locally advanced non?small cell lung cancer. In this prospective observational study, we evaluated the changes in peripheral blood immune cell counts to elucidate the immunologic mechanisms underlying cCRT and durvalumab therapy.
Experimental Design: Peripheral blood mononuclear cell (PBMC) samples were collected at four time points: before cCRT, after cCRT, at the start of durvalumab, and 8 weeks after the start of durvalumab, and analyzed by multicolor flow cytometry.
Results: Of the 149 enrolled patients, 115 received durvalumab consolidation therapy after cCRT. The median PFS in the overall population was 24.2 months, and the 3-year PFS rate was 38.9%. PBMC analysis showed an increased effector fraction of CD4+ T cells before and after cCRT but no change in CD8+ T cells. Following durvalumab therapy, the effector fraction ratio of CD8+ T cells (CD62Llow CD8+ T cells) increased and positively correlated with increased CD62Llow CD4+ T cells during cCRT. Patients whose proportion of CD62Llow CD4+ T cells exceeded the threshold for cCRT had better PFS than those below the threshold. Patients whose CD62Llow CD8+ T-cell proportion exceeded the threshold after durvalumab therapy showed prolonged PFS compared with those below the threshold.
Conclusions: cCRT promotes an increase in effector CD4+ T cells, and the subsequent increase in CD8+ T cells following durvalumab therapy prolongs PFS. Peripheral blood effector?type CD4+ and CD8+ T cells are potential biomarkers for evaluating the immune status of patients and predicting treatment efficacy. en-copyright= kn-copyright= en-aut-name=MouriAtsuto en-aut-sei=Mouri en-aut-mei=Atsuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KenmotsuHirotsugu en-aut-sei=Kenmotsu en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KagamuHiroshi en-aut-sei=Kagamu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AzumaKoichi en-aut-sei=Azuma en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoRyota en-aut-sei=Saito en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkamatsuHiroaki en-aut-sei=Akamatsu en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YonesakaKimio en-aut-sei=Yonesaka en-aut-mei=Kimio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KakegawaMikiko en-aut-sei=Kakegawa en-aut-mei=Mikiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagashimaHiromi en-aut-sei=Nagashima en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakahashiSatoshi en-aut-sei=Takahashi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujitaMasaki en-aut-sei=Fujita en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YanagitaniNoriko en-aut-sei=Yanagitani en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=NishiokaYasuhiko en-aut-sei=Nishioka en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MoriKeita en-aut-sei=Mori en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KitanoShigehisa en-aut-sei=Kitano en-aut-mei=Shigehisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TamadaKoji en-aut-sei=Tamada en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YamamotoNobuyuki en-aut-sei=Yamamoto en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 ORCID= en-aut-name=MitsudomiTetsuya en-aut-sei=Mitsudomi en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, International Medical Center, Saitama Medical University kn-affil= affil-num=2 en-affil=Division of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, International Medical Center, Saitama Medical University kn-affil= affil-num=4 en-affil=Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Tohoku University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= affil-num=7 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Kitasato University School of Medicine kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Iwate Medical University School of Medicine kn-affil= affil-num=10 en-affil=Department of Thoracic Surgery, Tokyo Medical University Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Fukuoka University Hospital kn-affil= affil-num=12 en-affil=Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=13 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=15 en-affil=Department of Biostatistics, Clinical Research Support Center, Shizuoka Cancer Center kn-affil= affil-num=16 en-affil=Department of Advanced Medical Development, The Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=17 en-affil=Department of Immunology, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= affil-num=19 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=20 en-affil=Division of Thoracic Surgery, Izumi City General Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=218 cd-vols= no-issue= article-no= start-page=109516 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=ULK1, a novel therapeutic target to delay drug tolerance to EGFR?TKIs in an EGFR-mutant non-small cell lung cancer model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The presence of drug-tolerant persister (DTP) cells reduces the effectiveness of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in EGFR-mutated non-small cell lung cancer (NSCLC). Although autophagy is a potential target for eliminating DTP cells, clinical trials targeting autophagy in EGFR-mutant NSCLC have been unsuccessful?likely because most trials have utilized chloroquine, non-specifically inhibiting autophagy targeting lysosomes with dose limitations. This study focused on unc-51-like autophagy activating kinase 1 (ULK1), a more specific target for autophagy inhibition, to assess whether ULK1 inhibition delays the emergence of tolerance to EGFR-tyrosine kinase inhibitors in EGFR-mutant NSCLC cells.
Methods: DTP cells were generated by treating EGFR-mutant NSCLC cell lines with osimertinib. Autophagy status and ULK1 expression were evaluated using immunofluorescence, western blotting, and quantitative real-time PCR. The effects of both pharmacological and genetic inhibition of ULK1 were examined in vitro and in vivo.
Results: ULK1 and LC3-II, markers of autophagy, were upregulated in DTP cells. Inhibition of ULK1, either pharmacologically or genetically, suppressed autophagy, prevented the formation of DTP cells, and enhanced the antitumor activity of osimertinib in both in vitro and in vivo models. Furthermore, upregulation of ULK1 expression through serum starvation conferred tolerance to osimertinib, reinforcing ULK1′s role in drug tolerance. Notably, ULK1 inhibition showed modest efficacy even after cells transitioned to the DTP or acquired resistance states.
Conclusion: ULK1 plays a critical role in mediating drug tolerance in EGFR-mutant NSCLC. Targeting ULK1 represents a promising therapeutic approach to enhance the efficacy of EGFR-TKIs and to delay the development of drug tolerance. en-copyright= kn-copyright= en-aut-name=MoritaAyako en-aut-sei=Morita en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=NishiTatsuya en-aut-sei=Nishi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaraNaofumi en-aut-sei=Hara en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OchiNobuaki en-aut-sei=Ochi en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Allergy and Respiratory 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 Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of General Internal Medicine 4, Kawasaki Medical School kn-affil= affil-num=13 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= en-keyword=ULK1 kn-keyword=ULK1 en-keyword=Autophagy kn-keyword=Autophagy en-keyword=EGFR kn-keyword=EGFR en-keyword=TKI kn-keyword=TKI en-keyword=Osimertinib kn-keyword=Osimertinib en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=6 article-no= start-page=315 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260527 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Limited Immune-Mediated Efficacy of Anti-PD-L1/VEGF in EGFR-TKI-Na?ve Egfr-Mutant Lung Cancer with Non-Inflamed Tumor Microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immune checkpoint inhibitors (ICIs) show limited efficacy in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma due to its non-inflamed tumor microenvironment (TME). While quadruple therapy combining chemotherapy, anti-programmed death-ligand 1 (PD-L1), and anti-vascular endothelial growth factor (VEGF) antibodies has shown inconsistent results in EGFR-tyrosine kinase inhibitor (TKI)-pretreated patients, whether anti-VEGF therapy can modulate the intrinsic non-inflamed TME remains unknown. We employed an EGFR-TKI-na?ve syngeneic Egfr-mutant mouse model and evaluated effects of anti-VEGF, anti-PD-L1, carboplatin, and paclitaxel as monotherapies and combinations, with TME analysis via immunohistochemistry (IHC), flow cytometry, and RNA sequencing. Anti-PD-L1 showed no antitumor effect, and adding anti-VEGF failed to convert the TME to an inflamed status. Although paclitaxel?but not carboplatin?combined with low-dose anti-VEGF inhibited tumor growth, adding anti-PD-L1 provided no benefit, indicating the anti-VEGF-A antibody evaluated here has a limited role in sensitizing tumors to anti-PD-L1 regardless of chemotherapy. CD8+ T-cell depletion did not attenuate the effect of paclitaxel plus low-dose anti-VEGF, and IHC and RNA sequencing revealed increased natural killer cell infiltration, suggesting a CD8+ T-cell-independent, innate immune mechanism. These findings provide preclinical evidence that the evaluated anti-VEGF has limited immunomodulatory activity in EGFR-TKI-na?ve Egfr-mutant tumors with a non-inflamed TME, and suggest immunotherapeutic strategies beyond CD8+ T-cell-mediated immunity warrant investigation. en-copyright= kn-copyright= en-aut-name=HirabaeAtsuko en-aut-sei=Hirabae en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=OkawaSachi en-aut-sei=Okawa en-aut-mei=Sachi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakasukaTakamasa en-aut-sei=Nakasuka en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishimuraJun en-aut-sei=Nishimura en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=SugimotoMasamichi en-aut-sei=Sugimoto en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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=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=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Respiratory 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 Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Product Research Department, Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=15 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=EGFR mutation kn-keyword=EGFR mutation en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=syngeneic mouse model kn-keyword=syngeneic mouse model en-keyword=antitumor immunity kn-keyword=antitumor immunity en-keyword=non-inflamed tumor kn-keyword=non-inflamed tumor en-keyword=VEGF kn-keyword=VEGF en-keyword=PD-L1 kn-keyword=PD-L1 END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=10 article-no= start-page=e70299 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=Interstitial Lung Disease in Patients With Unresectable Stage III NSCLC Treated With Chemoradiotherapy Followed by Durvalumab in Japan: Analysis From the Multicenter Prospective AYAME Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Interstitial lung disease (ILD) is a concerning adverse event associated with immune checkpoint inhibitors, including durvalumab. This analysis of the multicenter AYAME study assessed the longterm safety of durvalumab, focusing on ILD.
Methods: AYAME enrolled patients prescribed durvalumab for unresectable stage III non-small cell lung cancer (NSCLC) after chemoradiotherapy (CRT) from July 2019 to December 2020 in Japan. Patients received durvalumab for ??12?months and were prospectively followed for 3?years. Incidence, severity, and management of ILD were examined. Multivariable logistic regression analysis was conducted to investigate the association of patient characteristics with grade ??2 ILD occurrence.
Results: Of 511 patients in the safety analysis population, ILD occurred in 383 patients (75.0%) from durvalumab initiation to subsequent treatment start; median time to occurrence was 44.0?days. ILD led to permanent durvalumab discontinuation in 121/383 patients (31.6%), dose interruption in 111/383 (29.0%), and corticosteroid intervention in 168/383 (43.9%). Grade ??2 ILD occurrence was higher in patients with volume of lung parenchyma that received 20?Gy (V20) ??25% versus Conclusions: This study of durvalumab for NSCLC after CRT in a real-world setting indicated factors associated with grade ??2 ILD and provided valuable insights into ILD management strategies. These findings may contribute to establishing effective approaches to minimize ILD risk in practice.
Trial Registration: UMIN000037090/NCT03995875 en-copyright= kn-copyright= en-aut-name=YamamotoNobuyuki en-aut-sei=Yamamoto en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KenmotsuHirotsugu en-aut-sei=Kenmotsu en-aut-mei=Hirotsugu 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=AkdemirBurak en-aut-sei=Akdemir en-aut-mei=Burak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UematsuShinya en-aut-sei=Uematsu en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuiAyako en-aut-sei=Fukui en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KotoRyo en-aut-sei=Koto en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiwaraMasakazu en-aut-sei=Fujiwara en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwaoChikako en-aut-sei=Iwao en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitagawaHiroshi en-aut-sei=Kitagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 ORCID= en-aut-name=MitsudomiTetsuya en-aut-sei=Mitsudomi en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SaitoYoshinobu en-aut-sei=Saito en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= affil-num=2 en-affil=Division of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Oncology Medical, AstraZeneca K.K kn-affil= affil-num=5 en-affil=Oncology Medical, AstraZeneca K.K kn-affil= affil-num=6 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K kn-affil= affil-num=7 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K kn-affil= affil-num=8 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K kn-affil= affil-num=9 en-affil=Oncology Medical, AstraZeneca K.K kn-affil= affil-num=10 en-affil=Oncology Medical, AstraZeneca K.K kn-affil= affil-num=11 en-affil=Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital kn-affil= affil-num=12 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=13 en-affil=Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Pulmonary Medicine, Nippon Medical School Musashi Kosugi Hospital kn-affil= en-keyword=carcinoma kn-keyword=carcinoma en-keyword=chemoradiotherapy kn-keyword=chemoradiotherapy en-keyword=durvalumab kn-keyword=durvalumab en-keyword=interstitial kn-keyword=interstitial en-keyword=lung diseases kn-keyword=lung diseases en-keyword=non-small- cell lung kn-keyword=non-small- cell lung END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=1 article-no= start-page=160 end-page=173 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=Long-Term Safety and Effectiveness of Durvalumab in Unresectable Stage III NSCLC in Japan: A Multicenter Prospective Study (AYAME) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Based on the PACIFIC trial results, durvalumab after chemoradiotherapy (CRT) is the standard of care for unresectable stage III NSCLC. However, few large-scale studies have prospectively evaluated its long-term effectiveness and safety, including subsequent treatment.
Methods: This multicenter, noninterventional study (AYAME) enrolled patients who were prescribed durvalumab for unresectable stage III NSCLC after CRT (July 2019?December 2020; 52 sites; Japan). Patients received durvalumab for a maximum of 12 months and were prospectively followed up for 3 years, including the post-durvalumab treatment period. Primary end points were real-world progression-free survival (rwPFS), the incidence of interstitial lung disease (ILD), and adverse events of special interest (AESIs).
Results: Of the 529 enrolled patients, 512 received durvalumab and 511 comprised the safety analysis population. The median time to onset of the first presentation or occurrence of ILD was 45.0 days. ILD of any grade occurred in 387 patients (75.7%) over the 3-year study period: grade 3, 57 (11.2%); grade 4, none (0.0%); and grade 5, 9 (1.8%). The most common AESIs of any grade during durvalumab treatment were thyroid dysfunction (12.5%), hepatic dysfunction (7.2%), and colitis (2.0%). No durvalumab treatment-related ILD or AESIs occurred during the post-treatment period. The median [95% confidence interval] rwPFS was 23.2 [18.2, 27.2] months in the effectiveness analysis population (n = 495). rwPFS rates were 62.5%, 54.6%, 49.4%, and 40.4% at 12, 18, 24, and 36 months, respectively.
Conclusions: This first and largest prospective, observational study demonstrated the long-term safety and effectiveness of durvalumab for unresectable stage III NSCLC after CRT in a real-world clinical setting.
Clinical Trial Registration: UMIN000037090 and NCT03995875 en-copyright= kn-copyright= en-aut-name=KenmotsuHirotsugu en-aut-sei=Kenmotsu en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaitoYoshinobu en-aut-sei=Saito en-aut-mei=Yoshinobu 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=UematsuShinya en-aut-sei=Uematsu en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkdemirBurak en-aut-sei=Akdemir en-aut-mei=Burak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuiAyako en-aut-sei=Fukui en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KotoRyo en-aut-sei=Koto en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiwaraMasakazu en-aut-sei=Fujiwara en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwaoChikako en-aut-sei=Iwao en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitagawaHiroshi en-aut-sei=Kitagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 ORCID= en-aut-name=MitsudomiTetsuya en-aut-sei=Mitsudomi en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamamotoNobuyuki en-aut-sei=Yamamoto en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Division of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Nippon Medical School, Musashi Kosugi Hospital kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Oncology Medical, AstraZeneca K.K. kn-affil= affil-num=5 en-affil=Oncology Medical, AstraZeneca K.K. kn-affil= affil-num=6 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K. kn-affil= affil-num=7 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K. kn-affil= affil-num=8 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K. kn-affil= affil-num=9 en-affil=Oncology Medical, AstraZeneca K.K. kn-affil= affil-num=10 en-affil=Oncology Medical, AstraZeneca K.K. kn-affil= affil-num=11 en-affil=Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital kn-affil= affil-num=12 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=13 en-affil=Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine and Faculty of Medicine & Hospital kn-affil= affil-num=14 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= en-keyword=Durvalumab kn-keyword=Durvalumab en-keyword=Chemoradiotherapy kn-keyword=Chemoradiotherapy en-keyword=Interstitial lung disease kn-keyword=Interstitial lung disease en-keyword=Real-world evidence kn-keyword=Real-world evidence en-keyword=Unresectable stage III NSCLC kn-keyword=Unresectable stage III NSCLC END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=5 article-no= start-page=e84709 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250523 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phase II Study of Platinum Re-administration in Non-small Cell Lung Cancer Following Chemoimmunotherapy Resistance en-subtitle= kn-subtitle= en-abstract= kn-abstract=Platinum compounds represent standard treatments for various cancers. However, the efficacy of re-administrating platinum compounds has been demonstrated only in ovarian cancer and small cell lung cancer (SCLC), with its utility in non-small cell lung cancer (NSCLC) remaining unclear. Given that the prognosis of NSCLC has improved with effective treatments such as immune checkpoint inhibitors (ICIs), we propose a multicenter, single-arm, prospective phase II trial of re-administrating platinum-based combination therapy for NSCLC. Patients with NSCLC who have progressed after chemoimmunotherapy and exhibit a platinum-free interval of 85 days or more will receive carboplatin combination therapy. The drugs combined with carboplatin - pemetrexed, nab-paclitaxel, or gemcitabine - must not have been administered previously. The primary endpoint is progression-free survival (PFS), assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Assuming a threshold PFS of 4.2 months and an expected hazard ratio of 0.60, the required sample size is calculated as 40 patients to achieve 70% power with a 5% alpha error. Secondary endpoints included objective response rate, toxicity, and overall survival. This study will clarify the efficacy of re-administrating platinum compounds to patients with NSCLC who have developed resistance to chemoimmunotherapy. 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=HosokawaShinobu en-aut-sei=Hosokawa en-aut-mei=Shinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokoyamaToshihide en-aut-sei=Yokoyama en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugimotoKeisuke en-aut-sei=Sugimoto en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KudoKenichiro en-aut-sei=Kudo en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkadaToshiaki en-aut-sei=Okada en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaedaTadashi en-aut-sei=Maeda en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawaiHaruyuki en-aut-sei=Kawai en-aut-mei=Haruyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasugiMasayuki en-aut-sei=Yasugi en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 ORCID= en-aut-name=NinomiyaTakashi en-aut-sei=Ninomiya en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OzeIsao en-aut-sei=Oze en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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=16 ORCID= affil-num=1 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=3 en-affil=Respiratory Medicine, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=5 en-affil=Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= affil-num=6 en-affil=Respiratory Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=7 en-affil=Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=8 en-affil=Respiratory Medicine, National Hospital Organization Yamaguchi Ube Medical Center kn-affil= affil-num=9 en-affil=Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=10 en-affil=Respiratory Medicine, Chugoku Central Hospital kn-affil= affil-num=11 en-affil=Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=12 en-affil=Respiratory Medicine, Iwakuni Medical Center kn-affil= affil-num=13 en-affil=Respiratory Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=14 en-affil=Division of Molecular Medicine, Aichi Cancer Center Research Institute kn-affil= affil-num=15 en-affil=Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= en-keyword=carboplatin kn-keyword=carboplatin en-keyword=clinical trial kn-keyword=clinical trial en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=platinum-free interval kn-keyword=platinum-free interval en-keyword=re-administration kn-keyword=re-administration END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=2 article-no= start-page=e79601 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Elevated Plasma Progastrin-Releasing Peptide Levels Associated With the Diagnosis of Pulmonary Carcinoid Tumors: A Report of Two Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary carcinoids are the type of thoracic malignant tumors classified as neuroendocrine tumors. Case 1 involved a 59-year-old woman with a nodular shadow in the left upper pulmonary field observed on chest radiography. Chest computed tomography (CT) scan revealed a nodule in the left upper lobe and a soft tissue tumor near the left third rib. Given her elevated plasma progastrin-releasing peptide (ProGRP) level, a CT-guided biopsy was performed, confirming a diagnosis of pulmonary carcinoid with solitary bone metastasis. She subsequently underwent partial resection of the left upper lobe and the rib tumor. Case 2 involved a 67-year-old woman referred to our hospital after a chest CT scan revealed a nodule in the left lingular region. Her plasma ProGRP level was elevated, and a CT-guided biopsy confirmed a diagnosis of pulmonary carcinoid. As no lymph node metastases were detected, she underwent segmental resection of the left upper lobe. In both cases, plasma ProGRP levels decreased following surgical resection. These findings suggest that plasma ProGRP levels may serve as a useful diagnostic marker for pulmonary carcinoids. en-copyright= kn-copyright= en-aut-name=YamaokaTakashi en-aut-sei=Yamaoka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=NoumiTaku en-aut-sei=Noumi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoChiaki en-aut-sei=Matsumoto en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugimotoKeisuke en-aut-sei=Sugimoto en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= en-keyword=biopsy kn-keyword=biopsy en-keyword=case report kn-keyword=case report en-keyword=progrp kn-keyword=progrp en-keyword=pulmonary carcinoid kn-keyword=pulmonary carcinoid en-keyword=tumor marker kn-keyword=tumor marker END start-ver=1.4 cd-journal=joma no-vol=234 cd-vols= no-issue= article-no= start-page=112260 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The eukaryotic host?microbe?phage?nutrition interplay determines the bacterial effectors of supplemental lysine’s health benefits: An experimental cellular senescence model of digestive conditions in older adults en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recently, the consumption of various forms of the nutritive amino acid lysine (e.g., nutraceuticals and dietary supplements) has increased, particularly among the elderly, as it cannot be synthesized by the human body and plays a crucial role in several cellular physiological processes, including intestinal calcium and iron absorption, proteinogenesis, and fatty acid metabolism. However, the biochemical and immunological events that occur within the eukaryotic host-microbe-phage-nutrition interaction, especially when high amounts of lysine are consumed in nutraceutical or dietary supplement form by the elderly due to age-related requirements, as well as the impact on gut bacteria-derived metabolites, have not yet been fully studied. We hypothesized that (1) within an infectious-inflamed digestive milieu, the metabolism of excess extracellular lysine differs between young and senescent digestive cells, and (2) phages within the milieu exhibit alterations in host-microbe cometabolite signal profiles. To address this, we examined how gut microbes and phages, key regulators of eukaryotic host physiology, influence the immunometabolism of excess lysine. By combining two models of young and senescent digestive cells, the pathogenic P. aeruginosa PAO1, the Pseudomonas phage KPP22, and the anti-inflammatory bacterium Intestinimonas butyriciproducens, and simulating the pathogenesis of the interactive process of excessive lysine ingestion, we developed a five-way screening approach to explore key cell readouts, including viability, integrity, and function of the epithelial barrier, as well as cellular immunometabolic responses to exogenous lysine supplementation in cultures under infectious inflammation. Our findings are consistent with the possibility that host?microbe?microbe interactions involving lysine utilization and cross-feeding may influence the effects of lysine supplementation. These effects, whether beneficial or detrimental, can depend on the bacterial community, including the presence of pathogenic or potentially beneficial bacteria, interactions with intestinal phages, and the physiological conditions and metabolic requirements of the host and individual microbial taxa. en-copyright= kn-copyright= en-aut-name=GhadimiDarab en-aut-sei=Ghadimi en-aut-mei=Darab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Bl?merSophia en-aut-sei=Bl?mer en-aut-mei=Sophia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KAYAAysel ?AH?N en-aut-sei=KAYA en-aut-mei=Aysel ?AH?N kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Kr?gerSandra en-aut-sei=Kr?ger en-aut-mei=Sandra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=R?ckenChristoph en-aut-sei=R?cken en-aut-mei=Christoph kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Sch?ferHeiner en-aut-sei=Sch?fer en-aut-mei=Heiner kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=de HeerGeraldine en-aut-sei=de Heer en-aut-mei=Geraldine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=JarczakDominik en-aut-sei=Jarczak en-aut-mei=Dominik 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=MatsuzakiShigenobu en-aut-sei=Matsuzaki en-aut-mei=Shigenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=BockelmannWilhelm en-aut-sei=Bockelmann en-aut-mei=Wilhelm kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= affil-num=2 en-affil=Faculty of Medicine, Christian-Albrechts-University of Kiel kn-affil= affil-num=3 en-affil=Department of Nutrition and Dietetics, Faculty of Health Sciences, Antalya Bilim University kn-affil= affil-num=4 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=5 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=6 en-affil=Laboratory of Molecular Gastroenterology & Hepatology, Christian-Albrechts-University & UKSH Campus Kiel kn-affil= affil-num=7 en-affil=University Center for Nutritional Medicine, University Medical Centre Hamburg-Eppendorf kn-affil= affil-num=8 en-affil=University Center for Nutritional Medicine, University Medical Centre Hamburg-Eppendorf 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=Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University kn-affil= affil-num=11 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= en-keyword=Inflammaging kn-keyword=Inflammaging en-keyword=Lysine kn-keyword=Lysine en-keyword=Host cells kn-keyword=Host cells en-keyword=Phages kn-keyword=Phages en-keyword=Syntrophy kn-keyword=Syntrophy en-keyword=Cell senescence kn-keyword=Cell senescence 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=20260913 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical Significance of a Cell-Of-Origin-Based Classification in Pancreatic Ductal Adenocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with limited therapeutic options and poor clinical outcomes. Although PDAC has traditionally been thought to arise from ductal epithelial cells, recent studies using genetically engineered mouse models have demonstrated that acinar cells can also serve as a cell of origin, giving rise to tumors with distinct biological properties. Here, we investigated whether such lineage-specific differences are preserved in human PDAC. RNA sequencing was performed on resected specimens from 40 treatment-na?ve patients with PDAC, and tumors were classified into Acinar- and Ductal-subtypes using lineage-specific gene expression signatures derived from mouse models. This classification strategy was further applied to human PDAC cell lines, followed by in vitro drug sensitivity assays. Patients with Acinar-subtype tumors had significantly longer overall survival than those with Ductal-subtype tumors (median, 54.0 vs. 26.5?months; p? Methods: We retrospectively analyzed 225 nonagenarians undergoing surgical resection of CRC at 15 institutions between 2011 and 2022. Patients were stratified by GNRI-high/low status using two cutoffs: 98 (Cohort 1) and 86 (Cohort 2). Outcomes included postoperative complications, length of hospital stay, and overall survival (OS). Stabilized inverse-probability-of-treatment weighting (IPTW) was used to adjust for measured confounding.
Results: The median age was 92?years (female, 64.9%; colon cancer, 79.6%). GNRI-high patients had higher body mass index and albumin levels. Complication rates did not differ between the groups. After adjustment, GNRI-high patients in Cohort 1 had a shorter expected hospital stay (ratio 0.70, 95% CI 0.51?0.96; p?=?0.025) but no significant OS difference. In Cohort 2, GNRI-high patients had better OS (p? Conclusions: Preoperative GNRI was associated with hospital stay and OS in nonagenarians undergoing CRC surgery, although the OS association was significant only with the cohort-derived cutoff of 86, which requires external validation, and not with the literature-based cutoff of 98. The GNRI is a simple tool to stratify surgical risk and optimize perioperative nutritional status in this vulnerable population. en-copyright= kn-copyright= en-aut-name=ToshimaToshiaki en-aut-sei=Toshima en-aut-mei=Toshiaki 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=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=HoriNaoto en-aut-sei=Hori en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 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=12 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=13 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=14 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=15 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=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=The Setouchi Colorectal Neoplasm Registration Study Group en-aut-sei=The Setouchi Colorectal Neoplasm Registration Study Group 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, Kagawa Rosai Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital 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, Kochi Health Sciences Center 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 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 Hospital kn-affil= affil-num=20 en-affil= kn-affil= en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=geriatric nutritional risk index kn-keyword=geriatric nutritional risk index en-keyword=oldest-old patients kn-keyword=oldest-old patients en-keyword=overall survival kn-keyword=overall survival en-keyword=surgical outcome kn-keyword=surgical outcome END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=2 article-no= start-page=143 end-page=151 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240916 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cranial and spinal computed tomography (CT) angiography with photon-counting detector CT: comparison with angiographic and operative findings en-subtitle= kn-subtitle= en-abstract= kn-abstract=The clinical imaging features of photon-counting detector (PCD) computed tomography (CT) are mainly known as dose reduction, improvement of spatial resolution, and reduction of artifacts compared to energy-integrating detector CT (EID-CT). The utility of cranial and spinal PCD-CT and PCD-CT angiography (CTA) has been previously reported. CTA is a widely used technique for noninvasive evaluation. Cranial CTA is important in brain tumors, especially glioblastoma; it evaluates whether the tumor is highly vascularized prior to an operation and helps in the diagnosis and assessment of bleeding risk. Spinal CTA has an important role in the estimation of feeders and drainers prior to selective angiography in the cases of spinal epidural arteriovenous fistulas and spinal tumors, especially in hemangioblastoma. So far, EID-CTA is commonly performed in an adjunctive role prior to selective angiography; PCD-CTA with high spatial resolution can be an alternative to selective angiography. In the cases of cerebral aneurysms, flow diverters are important tools for the treatment of intracranial aneurysms, and postoperative evaluation with cone beam CT with angiography using diluted contrast media is performed to evaluate stent adhesion and in-stent thrombosis. If CTA can replace selective angiography, it will be less invasive for the patient. In this review, we present representative cases with PCD-CT. We also show how well the cranial and spinal PCD-CTA approaches the accuracy of angiographic and intraoperative findings. en-copyright= kn-copyright= en-aut-name=HigakiFumiyo en-aut-sei=Higaki en-aut-mei=Fumiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiramatsuMasafumi en-aut-sei=Hiramatsu en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasadaSusumu en-aut-sei=Sasada en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=HarumaJun en-aut-sei=Haruma en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=MorimitsuYusuke en-aut-sei=Morimitsu en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AkagiNoriaki en-aut-sei=Akagi en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuiYusuke en-aut-sei=Matsui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Radiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Radiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Photon-counting detector CT kn-keyword=Photon-counting detector CT en-keyword=Energy-integrating detector CT kn-keyword=Energy-integrating detector CT en-keyword=CT angiography kn-keyword=CT angiography en-keyword=Neuroimaging kn-keyword=Neuroimaging en-keyword=Spine kn-keyword=Spine END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=1534891 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250227 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy in Japanese adults with growth hormone deficiency receiving weekly somapacitan or daily growth hormone: results from phase 3 REAL 1 trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Somapacitan is a long-acting growth hormone (GH) derivative approved for once-weekly treatment of adult GH deficiency (AGHD). This study aimed to evaluate the efficacy and safety of somapacitan and daily GH in Japanese individuals with AGHD.
Methods: This subgroup study included the 34-week main period of the multinational, randomized, parallel-group, phase 3 trial, REAL 1 (NCT02229851). Participants received once-weekly somapacitan or daily GH (Norditropin?), both administered subcutaneously. Investigators and trial sites were blinded. A total of 36 Japanese GH-na?ve individuals with AGHD were allocated to somapacitan or daily GH (excluding the placebo group of the global trial). Endpoints included change in truncal fat percentage to week 34 measured using dual-energy x-ray absorptiometry, as well as other body composition measures. Insulin-like growth factor I standard deviation score values were used for dose titration.
Results: In total, 36 Japanese individuals were included (18 and 18 in the somapacitan and daily GH group, respectively). 35 completed the main period (34 weeks). Mean (SD) change from baseline to week 34 in truncal fat percentage was -2.23 (2.50) %-points in the somapacitan group and -2.12 (4.21) %-points in the daily GH group. Other body composition measures also improved in both groups, including reduced visceral fat and increased lean body mass. Somapacitan was well tolerated, with a safety profile similar to daily GH.
Conclusions: In Japanese treatment-na?ve individuals with AGHD, once-weekly somapacitan demonstrated similar efficacy and safety to daily GH after 34 weeks of treatment. Somapacitan provides an effective alternative to daily GH in AGHD. en-copyright= kn-copyright= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RasmussenMichael H?jby en-aut-sei=Rasmussen en-aut-mei=Michael H?jby kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EndoTakaaki en-aut-sei=Endo en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Sv?rkeClaus en-aut-sei=Sv?rke en-aut-mei=Claus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaharaShigeyuki en-aut-sei=Tahara en-aut-mei=Shigeyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JohannssonGudmundur en-aut-sei=Johannsson en-aut-mei=Gudmundur 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=Clinical Drug Development, Novo Nordisk A/S kn-affil= affil-num=3 en-affil=Medical Affairs Department, Novo Nordisk Pharma Ltd. kn-affil= affil-num=4 en-affil=Clinical Drug Development, Novo Nordisk A/S kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Nippon Medical School, Musashikosugi Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg and Department of Endocrinology, Diabetology, and Metabolism, Sahlgrenska University Hospital kn-affil= en-keyword=growth hormone kn-keyword=growth hormone en-keyword=adult growth hormone deficiency kn-keyword=adult growth hormone deficiency en-keyword=long-acting growth hormone kn-keyword=long-acting growth hormone en-keyword=somapacitan kn-keyword=somapacitan en-keyword=Japan kn-keyword=Japan END start-ver=1.4 cd-journal=joma no-vol=94 cd-vols= no-issue=1 article-no= start-page=1 end-page=18 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250311 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An XAI-based meta-parameter tuning for time-series forecasting en-subtitle= kn-subtitle= en-abstract= kn-abstract=How can we efficiently determine meta-parameter values for deep learning-based time-series forecasting given a time-series dataset? This paper introduces Xtune, an efficient and novel meta-parameter tuning method for deep learning-based time-series forecasting, leveraging explainable AI techniques. In particular, this study focuses on optimizing the window size for time-series forecasting. Xtune determines the optimal meta-parameter value for these methods and can also be applied to tune the window size for anomaly detection methods that utilize deep learning-based time-series forecasting. Extensive experiments on real-world datasets and forecasting methods demonstrate that Xtune efficiently identifies the optimal meta-parameter value and consistently outperforms the existing methods in terms of execution speed. en-copyright= kn-copyright= en-aut-name=NakagawaHiroyuki en-aut-sei=Nakagawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SumitaShimon en-aut-sei=Sumita en-aut-mei=Shimon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IidaRyuichi en-aut-sei=Iida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuchiyaTatsuhiro en-aut-sei=Tsuchiya en-aut-mei=Tatsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Osaka University kn-affil= affil-num=3 en-affil=Okayama University kn-affil= affil-num=4 en-affil=Osaka University kn-affil= en-keyword=Parameter optimization kn-keyword=Parameter optimization en-keyword=XAI kn-keyword=XAI en-keyword=Deep learning kn-keyword=Deep learning en-keyword=Time-series forecasting kn-keyword=Time-series forecasting en-keyword=Anomaly detection kn-keyword=Anomaly detection END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=30 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relationship Between Heated Tobacco Products and Placental Abruption: A Prospective Cohort Study Using Online Questionnaire en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Placental abruption (PA) is a critical obstetric complication, with maternal smoking recognized as a key risk factor. Despite the increased use of heated tobacco products (HTPs), the impact of HTPs remains unclear. This study investigated whether pregnant women using HTPs are at a higher risk of PA than non-users.
Methods: We analyzed data from “the Japan COVID-19 and Society Internet Survey,” a prospective, self-reported online survey cohort. Questionnaires were randomly distributed between July 28, 2021, and August 30, 2021. Pregnant respondents in 2021 were invited to complete an additional survey from February 14, 2022, to February 28, 2022. We set the outcome as the absolute risk difference (aRD) and relative risk ratio (rRR) of PA incidence due to smoking HTPs in the first trimester of pregnancy. The sample size included 12 836 participants. We calculated outcomes using a generalized linear model (GLM) and inverse probability of treatment weighting (IPTW). We also performed a Bayesian approach and multiple-bias analysis for sensitivity analysis.
Results: We found the robust aRD of 0.07 (95% confidence interval (CI): 0.06, 0.09) and the rRR of 11.3 (95% CI: 7.5, 17.0). Multiple bias analyses showed that unmeasurable confounders would need to have at least an rRR?=?14 relationship with both exposure and outcome to disprove the observed association. There has not been post hoc analysis or secondary use of data.
Conclusion: Early pregnancy use of HTPs is associated with an increased risk of PA. en-copyright= kn-copyright= en-aut-name=OobaHikaru en-aut-sei=Ooba en-aut-mei=Hikaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MakiJota en-aut-sei=Maki en-aut-mei=Jota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TabuchiTakahiro en-aut-sei=Tabuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= affil-num=1 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital 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=Division of Epidemiology, School of Public Health, Tohoku University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Placental abruption kn-keyword=Placental abruption en-keyword=Heated tobacco products kn-keyword=Heated tobacco products en-keyword=Pregnancy kn-keyword=Pregnancy en-keyword=Tobacco use kn-keyword=Tobacco use END start-ver=1.4 cd-journal=joma no-vol=980 cd-vols= no-issue=1 article-no= start-page=117 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250207 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Observing Supernova Neutrino Light Curves with Super-Kamiokande. V. Distance Estimation with Neutrinos en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neutrinos are pivotal signals in multimessenger observations of supernovae (SNe). Recent advancements in the analysis method of supernova (SN) neutrinos, especially in quantitative analysis, have significantly broadened scientific possibilities. This study demonstrates the feasibility of estimating distances to SNe using neutrinos. This estimation utilizes the direct relationship between the radius of a neutron star (NS) and the distance to the supernova, which is analogous to main-sequence fitting. The radius of an NS is determined with an approximate uncertainty of 10% through observations such as X-rays and gravitational waves. By integrating this information, the distance to the supernova can be estimated with an uncertainty of within 15% at a 95% confidence level. It has been established that neutrinos can pinpoint the direction of supernovae, and when combined with distance estimates, three-dimensional localization becomes achievable. This capability is vital for follow-up observations using multimessenger approaches. Moreover, more precise distance determinations to SNe through follow-up observations, such as optical observations, allow for accurate measurements of neutron-star radii. This data, via the neutron-star mass?radius relationship, could provide various insights into nuclear physics. en-copyright= kn-copyright= en-aut-name=SuwaYudai en-aut-sei=Suwa en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaradaAkira en-aut-sei=Harada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriMasamitsu en-aut-sei=Mori en-aut-mei=Masamitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakazatoKen’ichiro en-aut-sei=Nakazato en-aut-mei=Ken’ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkahoRyuichiro en-aut-sei=Akaho en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaradaMasayuki en-aut-sei=Harada en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KoshioYusuke en-aut-sei=Koshio en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanishiFumi en-aut-sei=Nakanishi en-aut-mei=Fumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SumiyoshiKohsuke en-aut-sei=Sumiyoshi en-aut-mei=Kohsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WendellRoger A. en-aut-sei=Wendell en-aut-mei=Roger A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Earth Science and Astronomy, The University of Tokyo kn-affil= affil-num=2 en-affil=Interdisciplinary Theoretical and Mathematical Sciences Program (iTHEMS), RIKEN kn-affil= affil-num=3 en-affil=Division of Science, National Astronomical Observatory of Japan kn-affil= affil-num=4 en-affil=Faculty of Arts and Science, Kyushu University kn-affil= affil-num=5 en-affil=Faculty of Science and Engineering, Waseda University kn-affil= affil-num=6 en-affil=Department of Physics, Okayama University kn-affil= affil-num=7 en-affil=Department of Physics, Okayama University kn-affil= affil-num=8 en-affil=Department of Physics, Okayama University kn-affil= affil-num=9 en-affil=National Institute of Technology, Numazu College kn-affil= affil-num=10 en-affil=Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU, WPI), Todai Institutes for Advanced Study, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=6 article-no= start-page=775 end-page=785 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=A Single-Arm Phase 2 Study of Sotorasib Plus Carboplatin and Pemetrexed in Patients With Advanced Nonsquamous NSCLC With KRAS G12C Mutation (WJOG14821L, SCARLET) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: The efficacy and safety of sotorasib plus platinum doublet chemotherapy in KRAS G12C-mutated nonsquamous NSCLC (nonsq NSCLC) have been previously reported with a limited follow-up period.
Methods: SCARLET is a single-arm phase 2 study involving chemotherapy-naive patients with KRAS G12C?mutated nonsq NSCLC. The participants received 960 mg daily plus four cycles of carboplatin (area under the curve = 5)/pemetrexed 500 mg/m2, followed by sotorasib/pemetrexed until disease progression. The primary end point was the overall response rate (ORR) and the secondary end points were progression-free survival (PFS), overall survival, and safety. Using plasma samples, next-generation sequencing was performed at baseline, 3 weeks, and during disease progression (the Japan Registry of Clinical Trials number 2051210086).
Results: Thirty patients were enrolled between October 2021 and July 2022 with a median follow-up of 14.8 months. ORR was 88.9% (80% confidence interval [CI]: 78.5%?94.8%, 95% CI: 70.8%?97.6%), median PFS was 6.6 months (95% CI: 5.3?16.7 mo), and median overall survival was 20.6 months (95% CI: 8.1 mo?not estimated). Among patients with programmed death-ligand 1 expression levels of 1% or higher and less than 1%, the ORRs were 82.3 and 100%, respectively, and the median PFS was 7.6 and 9.7 months, respectively. Using plasma samples, patients without KRAS G12C at baseline, without KRAS-related pathway co-alterations, or who cleared KRAS G12C at 3 weeks had better median PFS (16.7, 13.9, 8.7 mo, respectively). Tumor protein 53 mutations and EGFR and MET amplification were detected as acquired resistance.
Conclusions: In patients with KRAS G12C-mutated nonsq NSCLC, sotorasib plus carboplatin/pemetrexed reported favorable efficacy, particularly for patients with less than 1% programmed death-ligand 1, with manageable toxicity. en-copyright= kn-copyright= en-aut-name=AkamatsuHiroaki en-aut-sei=Akamatsu en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=AzumaKoichi en-aut-sei=Azuma en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UemuraTakehiro en-aut-sei=Uemura en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Tsuchiya-KawanoYuko en-aut-sei=Tsuchiya-Kawano en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EsumiSeiya en-aut-sei=Esumi en-aut-mei=Seiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KurosakiTakashi en-aut-sei=Kurosaki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoYuki en-aut-sei=Sato en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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=12 ORCID= en-aut-name=YoneshimaYasuto en-aut-sei=Yoneshima en-aut-mei=Yasuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShukuyaTakehito en-aut-sei=Shukuya en-aut-mei=Takehito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KozukiToshiyuki en-aut-sei=Kozuki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=WatanabeKana en-aut-sei=Watanabe en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=DagaHaruko en-aut-sei=Daga en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KatoTerufumi en-aut-sei=Kato en-aut-mei=Terufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OsugaMitsuo en-aut-sei=Osuga en-aut-mei=Mitsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KohYasuhiro en-aut-sei=Koh en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 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=22 ORCID= en-aut-name=YamamotoNobuyuki en-aut-sei=Yamamoto en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Kumamoto University Hospital kn-affil= affil-num=3 en-affil=Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine kn-affil= affil-num=4 en-affil=Department of Thoracic Oncology, Kansai Medical University kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Kitakyushu Municipal Medical Center kn-affil= affil-num=7 en-affil=Respiratory Center, Matsusaka Municipal Hospital kn-affil= affil-num=8 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Kobe City Medical Center General Hospital kn-affil= affil-num=10 en-affil=Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=11 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Thoracic Oncology, NHO Kyushu Cancer Center kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Juntendo University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center kn-affil= affil-num=16 en-affil=Department of Respiratory Medicine, Miyagi Cancer Center kn-affil= affil-num=17 en-affil=Department of Medical Oncology, Osaka City General Hospital kn-affil= affil-num=18 en-affil=Department of Thoracic Oncology, Kanagawa Cancer Center kn-affil= affil-num=19 en-affil=Division of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=20 en-affil=Center for Biomedical Sciences, Wakayama Medical University kn-affil= affil-num=21 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= affil-num=22 en-affil=Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine kn-affil= affil-num=23 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= en-keyword=KRAS G12C kn-keyword=KRAS G12C en-keyword=Sotorasib kn-keyword=Sotorasib en-keyword=Nonsquamous non?small cell lung cancer kn-keyword=Nonsquamous non?small cell lung cancer END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue= article-no= start-page=1 end-page=16 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=Clinical impact of hypomagnesemia induced by necitumumab plus cisplatin and gemcitabine treatment in patients with advanced lung squamous cell carcinoma: a subanalysis of the NINJA study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The clinical impact of hypomagnesemia induced by necitumumab plus gemcitabine and cisplatin (GCN) as a second-line or later therapy is unclear.
Objective: We aimed to evaluate the clinical characteristics and survival impact of hypomagnesemia induced by this therapy.
Design: This was a sub-analysis of the retrospective multicenter NINJA study.
Methods: Among the 93 patients enrolled in the NINJA study, this subanalysis included 75 patients with baseline serum magnesium concentrations.
Results: The incidence of grade ?2 hypomagnesemia was 18.0% in the patients with normal baseline serum magnesium concentrations and 42.8% in those with low concentrations (p?=?0.073). The discontinuation rates of GCN treatment owing to hypomagnesemia in each group were 0% and 7.1%, respectively (p?=?0.187). The number of necitumumab doses and severity of hypomagnesemia were positively correlated (r?=?0.389, p? Conclusion: GCN as a second-line or later therapy may be tolerable regardless of the patient’s baseline serum magnesium concentration. On the other hand, early serum magnesium reduction with this therapy is associated with a poor prognosis. However, caution should be needed because our results lacked sufficient information for confounding variables other than those analyzed here that may influence the correlation between hypomagnesemia and survival. en-copyright= kn-copyright= en-aut-name=TanzawaShigeru en-aut-sei=Tanzawa en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=5 ORCID= en-aut-name=MurataYasunori en-aut-sei=Murata en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeshitaMasafumi en-aut-sei=Takeshita en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KinoshitaFumihiko en-aut-sei=Kinoshita en-aut-mei=Fumihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujishitaTakatoshi en-aut-sei=Fujishita en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugawaraShunichi en-aut-sei=Sugawara en-aut-mei=Shunichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawashimaYosuke en-aut-sei=Kawashima en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HashimotoKazuki en-aut-sei=Hashimoto en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MoriMasahide en-aut-sei=Mori en-aut-mei=Masahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MiyanagaAkihiko en-aut-sei=Miyanaga en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HayashiAnna en-aut-sei=Hayashi en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TanakaHisashi en-aut-sei=Tanaka en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HondaRyoichi en-aut-sei=Honda en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NojiriMasafumi en-aut-sei=Nojiri en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SatoYuki en-aut-sei=Sato en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 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=20 ORCID= en-aut-name=IshikawaNobuhisa en-aut-sei=Ishikawa en-aut-mei=Nobuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KozukiToshiyuki en-aut-sei=Kozuki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KawamuraTakahisa en-aut-sei=Kawamura en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=SaitoGo en-aut-sei=Saito en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YamaguchiTeppei en-aut-sei=Yamaguchi en-aut-mei=Teppei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=AsadaKazuhiro en-aut-sei=Asada en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TetsumotoSatoshi en-aut-sei=Tetsumoto en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=TanakaHiroshi en-aut-sei=Tanaka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=WatanabeSatoshi en-aut-sei=Watanabe en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=UmedaYukihiro en-aut-sei=Umeda en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=YamaguchiKakuhiro en-aut-sei=Yamaguchi en-aut-mei=Kakuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=TsurunoKosuke en-aut-sei=Tsuruno en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=MisumiYuki en-aut-sei=Misumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=KuraishiHiroshi en-aut-sei=Kuraishi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=YoshiharaKen en-aut-sei=Yoshihara en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=NakaoAkira en-aut-sei=Nakao en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=KuboAkihito en-aut-sei=Kubo en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=YokoyamaToshihiko en-aut-sei=Yokoyama en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=WatanabeKana en-aut-sei=Watanabe en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=SekiNobuhiko en-aut-sei=Seki en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= affil-num=1 en-affil=Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine kn-affil= affil-num=2 en-affil=Department of Thoracic Oncology, Kansai Medical University Hospital kn-affil= affil-num=3 en-affil=Department of Data Science, National Cancer Center Hospital East kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Tohoku University Hospital kn-affil= affil-num=5 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Ichinomiya Nishi Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Ichinomiya Nishi Hospital kn-affil= affil-num=8 en-affil=Department of Thoracic Oncology, NHO Kyushu Cancer Center kn-affil= affil-num=9 en-affil=Department of Thoracic Oncology, NHO Kyushu Cancer Center kn-affil= affil-num=10 en-affil=Department of Pulmonary Medicine, Sendai Kousei Hospital kn-affil= affil-num=11 en-affil=Department of Pulmonary Medicine, Sendai Kousei Hospital kn-affil= affil-num=12 en-affil=Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center kn-affil= affil-num=13 en-affil=Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center kn-affil= affil-num=14 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=15 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=16 en-affil=Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Asahi General Hospital kn-affil= affil-num=18 en-affil=Department of Respiratory Medicine, Kanazawa Medical University kn-affil= affil-num=19 en-affil=Department of Respiratory Medicine, Kobe City Medical Center General Hospital kn-affil= affil-num=20 en-affil=Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center kn-affil= affil-num=21 en-affil=Department of Respiratory Medicine, Hiroshima Prefectural Hospital kn-affil= affil-num=22 en-affil=Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center kn-affil= affil-num=23 en-affil=Department of Thoracic Oncology, Osaka International Cancer Institute kn-affil= affil-num=24 en-affil=Department of Respirology, Graduate School of Medicine, Chiba University kn-affil= affil-num=25 en-affil=Department of Thoracic Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=26 en-affil=Department of Respiratory Medicine, Shizuoka General Hospital kn-affil= affil-num=27 en-affil=Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital kn-affil= affil-num=28 en-affil=Department of Internal Medicine, Niigata Cancer Center Hospital kn-affil= affil-num=29 en-affil=Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=30 en-affil=Department of Respiratory Medicine, Faculty of Medical Sciences, University of Fukui kn-affil= affil-num=31 en-affil=Department of Respiratory Medicine, Hiroshima University Hospital kn-affil= affil-num=32 en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center, Iwakuni, Yamaguchi, Japan kn-affil= affil-num=33 en-affil=Department of Respiratory Medicine, Iizuka Hospital kn-affil= affil-num=34 en-affil=Department of Respiratory Medicine, Yokohama Municipal Citizen’s Hospital kn-affil= affil-num=35 en-affil=Department of Pulmonary Medicine, Nagano Red Cross Hospital kn-affil= affil-num=36 en-affil=Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine kn-affil= affil-num=37 en-affil=Department of Respiratory Medicine, Fukuoka University Hospital kn-affil= affil-num=38 en-affil=Department of Respiratory Medicine and Allergology, Aichi Medical University kn-affil= affil-num=39 en-affil=Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital kn-affil= affil-num=40 en-affil=Department of Respiratory Medicine, Miyagi Cancer Center kn-affil= affil-num=41 en-affil=Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine kn-affil= en-keyword=adverse event kn-keyword=adverse event en-keyword=hypomagnesemia kn-keyword=hypomagnesemia en-keyword=lung squamous cell carcinoma kn-keyword=lung squamous cell carcinoma en-keyword=necitumumab kn-keyword=necitumumab en-keyword=prognosis kn-keyword=prognosis END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=1 article-no= start-page=5 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250213 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association Between Alcohol Use Patterns and Insomnia Symptoms or Poor Sleep Quality Among Adult Women: An Internet Cross-Sectional Survey in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=It is unclear whether patterns of alcohol consumption are associated with sleep disturbance. We aimed to investigate the relationship between comprehensive alcohol-related factors and insomnia symptoms, as well as sleep quality, among adult women in Japan. Responses to an online cross-sectional survey were gathered from 12,000 women. The survey items included demographic characteristics, alcohol consumption (Alcohol Use Disorders Identification Test, nightcaps, years of drinking), sleep-related factors (sleep duration, insomnia symptoms, sleep quality), lifestyle-related factors, and mental health. Binary logistic regression was used to investigate the relationship between alcohol consumption and both insomnia symptoms and sleep quality. A total of 10,233 women were included in the final analysis. The results revealed that several alcohol-related behaviors, including the consumption of nightcaps and years of drinking, were significantly associated with insomnia symptoms and poor sleep quality. Specifically, nightcaps were significantly associated with all types of insomnia symptoms and poor sleep quality, with a higher odds ratio than other alcohol-related items. Our findings suggest that specific alcohol-related behaviors, particularly the consumption of nightcaps, are associated with insomnia symptoms and poor sleep quality among women. Intervention programs for alcohol consumption should be provided to prevent sleep problems among women. en-copyright= kn-copyright= en-aut-name=NakajimaSuguru en-aut-sei=Nakajima en-aut-mei=Suguru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 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=5 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=6 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=7 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=8 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=9 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=10 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=11 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=12 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=13 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=14 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=15 ORCID= affil-num=1 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=2 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=3 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=4 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine 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=National Hospital Organization Kurihama Medical and Addiction Center kn-affil= affil-num=8 en-affil=National Hospital Organization, Ryukyu Hospital kn-affil= affil-num=9 en-affil=National Hospital Organization Kurihama Medical and Addiction Center kn-affil= affil-num=10 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Family Medicine, General Practice and Community Health, Faculty of Medicine, University of Tsukuba kn-affil= affil-num=12 en-affil=Department of Food Science and Nutrition, Faculty of Life and Environmental Science, Showa Women’s University kn-affil= affil-num=13 en-affil=Department of Hygiene and Preventive Medicine, Fukushima Medical University kn-affil= affil-num=14 en-affil=Department of Food and Nutrition, Koriyama Women’s University kn-affil= affil-num=15 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= en-keyword=alcohol drinking kn-keyword=alcohol drinking en-keyword=female kn-keyword=female en-keyword=sleep duration kn-keyword=sleep duration en-keyword=sleep quality kn-keyword=sleep quality END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=263 end-page=267 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Preoperative Nutritional Status Influences Enteral Nutrition Weaning 6 Months Post-Surgery in Patients with Esophageal Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: This study aimed to clarify whether nutritional status at admission affects enteral nutrition weaning 6 months after surgery in patients with esophageal cancer. Methods: This was a retrospective study of 81 patients who underwent subtotal esophageal cancer resection between April 2014 and February 2016. The survey items were as follows: 1) sex, 2) age, 3) presence or absence of family members living together, 4) clinical stage, 5) surgical procedure, 6) reconstructed organs, 7) nutritional status at admission, 8) presence or absence of postoperative complications (anastomotic leakage, chylothorax, and recurrent laryngeal nerve paralysis), and 9) presence or absence of treatment other than surgery (chemo- or radiotherapy). Results: The enteral nutrition withdrawal rate after 6 months was 15.5% in the malnutrition group and 84.5% in the normal nutrition group (p = 0.007). In a comparison between groups with and without enteral nutrition after 6 months, a significant association was observed with surgical procedure, nutritional status at admission, and postoperative complications (p < 0.05). Logistic regression analysis showed that the odds of discontinuing enteral nutrition 6 months later were 5.692 (hazard ratio: 1.545?20.962) for malnutrition on admission and 11.921 (hazard ratio: 3.449?41.207) for complications. Conclusion: Regardless of the presence or absence of treatment other than surgery, preoperative nutritional improvement is beneficial for increasing postoperative oral intake. en-copyright= kn-copyright= en-aut-name=SonoiMika en-aut-sei=Sonoi en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SonoiNorihiro en-aut-sei=Sonoi en-aut-mei=Norihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Foods and Human Nutrition, Faculty of Human Life Sciences, Notre Dame Seishin University kn-affil= affil-num=2 en-affil=Department of Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=3 en-affil=Center for Education in Medicine and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Enteral nutrition kn-keyword=Enteral nutrition en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=Geriatric nutritional risk index kn-keyword=Geriatric nutritional risk index en-keyword=Preoperative management kn-keyword=Preoperative management en-keyword=Preoperative nutritional status kn-keyword=Preoperative nutritional status END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue= article-no= start-page=1 end-page=13 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=Skin disorder within 30?days is a favorable prognostic factor in patients with lung squamous cell carcinoma treated with necitumumab plus gemcitabine and cisplatin: a sub-analysis of the NINJA study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Skin disorders are major adverse events associated with necitumumab plus gemcitabine and cisplatin (Neci?+?GC) administration. However, the prognostic effect of skin disorders in patients with lung squamous cell carcinoma (LSCC) administered Neci?+?GC is unclear.
Objectives: We examined this prognostic effect in patients with LSCC, and the usefulness of minocycline administration.
Design: This was a sub-analysis of the retrospective multicenter NINJA study.
Methods: We performed a landmark survival analysis according to the presence of skin disorders at Day 30 of treatment and examined the usefulness of minocycline for treating skin disorders.
Results: Among the 93 patients, 62 (66.7%) had a skin disorder at Day 30. Nineteen, 30, and 13 patients experienced Grade 1, 2, and 3 skin disorders, respectively. The overall survival (OS) and progression-free survival (PFS) of patients with skin disorders at Day 30 were longer than those of patients without skin disorders (median OS: 434 vs 278?days, p?=?0.0201; median PFS: 148 vs 82?days, p?=?0.0835). Multivariable analysis showed that a skin disorder at Day 30 was an independent prognostic factor for both OS (p?=?0.0044) and PFS (p?=?0.0514). Of the 62 patients with skin disorders at Day 30, 38 (61.3%) were taking minocycline, and their time to treatment failure (TTF) was better than that in patients not taking minocycline (median TTF: 148 vs 101?days, p?=?0.0495).
Conclusion: A skin disorder within 30?days was a favorable prognostic factor for patients with LSCC administered Neci?+?GC. Additionally, minocycline administration may be beneficial in patients who develop skin disorders within 30?days. en-copyright= kn-copyright= en-aut-name=KinoshitaFumihiko en-aut-sei=Kinoshita en-aut-mei=Fumihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanzawaShigeru en-aut-sei=Tanzawa en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 ORCID= en-aut-name=MurataYasunori en-aut-sei=Murata en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeshitaMasafumi en-aut-sei=Takeshita en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=SugawaraShunichi en-aut-sei=Sugawara en-aut-mei=Shunichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawashimaYosuke en-aut-sei=Kawashima en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HashimotoKazuki en-aut-sei=Hashimoto en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MoriMasahide en-aut-sei=Mori en-aut-mei=Masahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MiyanagaAkihiko en-aut-sei=Miyanaga en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HayashiAnna en-aut-sei=Hayashi en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TanakaHisashi en-aut-sei=Tanaka en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HondaRyoichi en-aut-sei=Honda en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NojiriMasafumi en-aut-sei=Nojiri en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SatoYuki en-aut-sei=Sato en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YamamotoKen en-aut-sei=Yamamoto en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MasudaKen en-aut-sei=Masuda en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KozukiToshiyuki en-aut-sei=Kozuki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KawamuraTakahisa en-aut-sei=Kawamura en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=SuzukiTakuji en-aut-sei=Suzuki en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YamaguchiTeppei en-aut-sei=Yamaguchi en-aut-mei=Teppei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=AsadaKazuhiro en-aut-sei=Asada en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TetsumotoSatoshi en-aut-sei=Tetsumoto en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=TanakaHiroshi en-aut-sei=Tanaka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=WatanabeSatoshi en-aut-sei=Watanabe en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=UmedaYukihiro en-aut-sei=Umeda en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=YamaguchiKakuhiro en-aut-sei=Yamaguchi en-aut-mei=Kakuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 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=32 ORCID= en-aut-name=TsurunoKosuke en-aut-sei=Tsuruno en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=MisumiYuki en-aut-sei=Misumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=KuraishiHiroshi en-aut-sei=Kuraishi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=YoshiharaKen en-aut-sei=Yoshihara en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=NakaoAkira en-aut-sei=Nakao en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=KuboAkihito en-aut-sei=Kubo en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=YokoyamaToshihiko en-aut-sei=Yokoyama en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=WatanabeKana en-aut-sei=Watanabe en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=SekiNobuhiko en-aut-sei=Seki en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, NHO Kyushu Cancer Center kn-affil= affil-num=2 en-affil=Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine kn-affil= affil-num=3 en-affil=Department of Data Science, National Cancer Center Hospital East kn-affil= affil-num=4 en-affil=Department of Thoracic Oncology, Kansai Medical University kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Tohoku University Hospital kn-affil= affil-num=6 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Ichinomiya Nishi Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Ichinomiya Nishi Hospital kn-affil= affil-num=9 en-affil=Department of Thoracic Oncology, NHO Kyushu Cancer Center kn-affil= affil-num=10 en-affil=Department of Pulmonary Medicine, Sendai Kousei Hospital kn-affil= affil-num=11 en-affil=Department of Pulmonary Medicine, Sendai Kousei Hospital kn-affil= affil-num=12 en-affil=Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center kn-affil= affil-num=13 en-affil=Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center kn-affil= affil-num=14 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=15 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=16 en-affil=Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Asahi General Hospital kn-affil= affil-num=18 en-affil=Department of Respiratory Medicine, Kanazawa Medical University kn-affil= affil-num=19 en-affil=Department of Respiratory Medicine, Kobe City Medical Center General Hospital kn-affil= affil-num=20 en-affil=Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center kn-affil= affil-num=21 en-affil=Department of Respiratory Medicine, Hiroshima Prefectural Hospital kn-affil= affil-num=22 en-affil=Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center kn-affil= affil-num=23 en-affil=Department of Thoracic Oncology, Osaka International Cancer Institute kn-affil= affil-num=24 en-affil=Department of Respirology, Graduate School of Medicine, Chiba University kn-affil= affil-num=25 en-affil=Department of Thoracic Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=26 en-affil=Department of Respiratory Medicine, Shizuoka General Hospital kn-affil= affil-num=27 en-affil=Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital kn-affil= affil-num=28 en-affil=Department of Internal Medicine, Niigata Cancer Center Hospital kn-affil= affil-num=29 en-affil=Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=30 en-affil=Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui kn-affil= affil-num=31 en-affil=Department of Respiratory Medicine, Hiroshima University Hospital kn-affil= affil-num=32 en-affil=Department of Respiratory medicine, NHO Iwakuni Clinical Center kn-affil= affil-num=33 en-affil=Department of Respiratory Medicine, Iizuka Hospital kn-affil= affil-num=34 en-affil=Department of Respiratory Medicine, Yokohama Municipal Citizen’s Hospital kn-affil= affil-num=35 en-affil=Department of Respiratory Medicine, Nagano Red Cross Hospital kn-affil= affil-num=36 en-affil=Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine kn-affil= affil-num=37 en-affil=Department of Respiratory Medicine, Fukuoka University Hospital kn-affil= affil-num=38 en-affil=Department of Respiratory Medicine and Allergology, Aichi Medical University School of Medicine kn-affil= affil-num=39 en-affil=Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital kn-affil= affil-num=40 en-affil=Department of Respiratory Medicine, Miyagi Cancer Center kn-affil= affil-num=41 en-affil=Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine kn-affil= en-keyword=adverse event kn-keyword=adverse event en-keyword=lung cancer kn-keyword=lung cancer en-keyword=necitumumab kn-keyword=necitumumab en-keyword=skin disorder kn-keyword=skin disorder en-keyword=squamous cell carcinoma kn-keyword=squamous cell carcinoma END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=9 article-no= start-page=2110 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260921 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Virotherapy for Spinal and Spinal Cord Tumors: Current Evidence and Future Perspectives en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tumors of the spine and spinal cord, including primary and metastatic vertebral tumors, intramedullary gliomas, and refractory intradural lesions, are challenging to treat because curative local therapy is limited by the eloquent, nonregenerating neural tissue surrounding them. Oncolytic virotherapy may offer a rational alternative by combining tumor-selective oncolysis with the induction of systemic antitumor immunity, while sparing normal neural cells. This review summarizes the current field of oncolytic viruses, including adenovirus, herpes simplex virus, reovirus, and others, in the context of spinal and spinal cord tumors. Clinical data in the spine remain scarce; however, the rationale is based on histological evidence from sarcomas and other tumors, extensive glioma experience, including diffuse intrinsic pontine glioma, and preclinical activity in nerve sheath and meningioma models. We discuss the telomerase-specific oncolytic adenovirus OBP-301 and its derivatives, whose hTERT-driven replication provides histology-agnostic tumor selectivity, while sparing the telomerase-silent spinal cord. This telomerase dependence, however, limits activity against tumors that maintain telomeres through the alternative lengthening of telomeres (ALT) pathway, such as many osteosarcomas and some spinal cord astrocytomas. We also discuss delivery and safety within the confined spinal canal, combination strategies, and future directions, such as extracellular vesicle-mediated delivery and biomarker-guided patient selection. Although clinical translation to the spine will require dedicated preclinical and early-phase studies, virotherapy represents a promising, mechanistically grounded modality for these therapeutically challenging tumors. en-copyright= kn-copyright= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakatoriRyo en-aut-sei=Takatori en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=MatsumotoKenzaburo en-aut-sei=Matsumoto en-aut-mei=Kenzaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=ShinoharaKensuke en-aut-sei=Shinohara en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=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=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, 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 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 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 Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=oncolytic virotherapy kn-keyword=oncolytic virotherapy en-keyword=spinal cord tumor kn-keyword=spinal cord tumor en-keyword=spinal metastasis kn-keyword=spinal metastasis en-keyword=oncolytic adenovirus kn-keyword=oncolytic adenovirus en-keyword=OBP-301 kn-keyword=OBP-301 en-keyword=hTERT kn-keyword=hTERT en-keyword=telomerase kn-keyword=telomerase en-keyword=glioma kn-keyword=glioma en-keyword=blood?spinal cord barrier kn-keyword=blood?spinal cord barrier en-keyword=cancer immunotherapy kn-keyword=cancer immunotherapy END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue=10 article-no= start-page=e70808 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260923 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Conformational stability and domain‐specific structural features of tumor autoantigens regulate autoantibody epitope propensity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Autoantibodies against tumor-associated autoantigens are clinically valuable biomarkers for cancer diagnosis; however, the structural determinants governing epitope selectivity remain unknown. Here, we investigated whether the intrinsic conformational stability of target autoantigens regulates the epitope propensity of tumor-associated autoantibodies in non-small cell lung cancer. Using a dual-antigen Luminex bead-based assay that presents each autoantigen in both native and S-cationized denatured forms, we directly compared IgG autoantibody reactivity toward conformational and linear epitopes across 11 autoantigens. Intrinsically disordered aggregation-prone autoantigens, including cancer/testis antigens, NY-ESO-1, and XAGE-1b, predominantly elicit linear epitope-directed responses, whereas thermodynamically stable soluble autoantigens generally drive conformational epitope recognition. Intriguingly, for autoantigens harboring both ordered and disordered segments, the immune response is strictly guided by domain-specific biophysics: while p53-specific antibodies preferentially target their flanking disordered regions, the Wilms' tumor protein 1 exceptionally drives conformational recognition directed toward its structured zinc-finger domains. Recombinant solubility in Escherichia coli broadly correlated with epitope class across all 11 autoantigens, confirming that prokaryotic folding efficiency generally reflects intrinsic conformational stability in vivo for autonomously folding monomeric cytosolic proteins. Independent computational validation was provided by the concordance between the experimental solubility ratios and AlphaFold3-derived Rosetta energy unit/solvent-accessible surface area values, demonstrating the convergence of thermodynamic estimates and patient-derived immune data within a unifying biophysical framework. These findings establish that the autoantibody epitope propensity is closely associated with the thermodynamic stability of the target autoantigen and provide a rational basis for tailoring antigen preparation strategies for autoantibody-based cancer diagnosis. en-copyright= kn-copyright= en-aut-name=MiyamotoAi en-aut-sei=Miyamoto en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoRika en-aut-sei=Yamamoto en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakaguchiRyui en-aut-sei=Sakaguchi en-aut-mei=Ryui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=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=WatanabeHiromi en-aut-sei=Watanabe en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 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=14 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=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=autoantibody kn-keyword=autoantibody en-keyword=biomarker kn-keyword=biomarker en-keyword=cancer/testis antigen kn-keyword=cancer/testis antigen en-keyword=epitope propensity kn-keyword=epitope propensity en-keyword=intrinsically disordered regions kn-keyword=intrinsically disordered regions en-keyword=protein engineering kn-keyword=protein engineering en-keyword=tumor-associated antigens kn-keyword=tumor-associated antigens END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=9 article-no= start-page=e70208 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Proton‐Radiation‐Tolerant Silicon Photonic Charge Sensor for Spacecraft Applications en-subtitle= kn-subtitle= en-abstract= kn-abstract=Silicon waveguides are promising platforms for spacecraft potential sensing owing to their compactness and immunity to electromagnetic interference. However, proton-induced optical absorption in operating silicon waveguides has not been quantitatively clarified, despite their direct exposure to the space radiation environment during spacecraft operation. Here, we present a systematic elucidation of proton-radiation effects on a photonic charge sensor based on silicon photonic crystal waveguides. During proton irradiation at 20 keV, we quantitatively evaluate the increase in optical absorption under device operation and find that a fluence of 1.0 ×1014 cm? 2 induces an additional absorption coefficient of approximately 0.41 cm? 1 . We further demonstrate that the sensor retains its ability to measure spacecraft potential even after exposure to a high proton fluence of 1.0 ×1015 cm? 2 , confirming its intrinsic radiation tolerance. These results establish the radiation robustness of silicon-waveguide- based sensing mechanisms and provide the first quantitative basis for implementing photonic charge sensors in radiation-rich spacecraft environments. en-copyright= kn-copyright= en-aut-name=TakahamaWataru en-aut-sei=Takahama en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtsukaKosei en-aut-sei=Otsuka en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshiharaAyumi en-aut-sei=Ishihara en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HojoRikuto en-aut-sei=Hojo en-aut-mei=Rikuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MogamiTomofumi en-aut-sei=Mogami en-aut-mei=Tomofumi 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=SuzukiKohtaku en-aut-sei=Suzuki en-aut-mei=Kohtaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakahashiYasushi en-aut-sei=Takahashi en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Physics and Electronics, Osaka Metropolitan University kn-affil= affil-num=2 en-affil=Department of Physics and Electronics, Osaka Metropolitan University kn-affil= affil-num=3 en-affil=Department of Physics and Electronics, Osaka Metropolitan University kn-affil= affil-num=4 en-affil=Department of Space Systems Engineering, Kyushu Institute of Technology kn-affil= affil-num=5 en-affil=ElectrostaticEngineering DEPT, Kasuga Denki INC kn-affil= affil-num=6 en-affil=Department of Space Systems Engineering, Kyushu Institute of Technology kn-affil= affil-num=7 en-affil=Research and Development, The Wakasa Wan Energy Research Center kn-affil= affil-num=8 en-affil=Faculty of Environmental, Life, Natural Science and Technology,Okayama University kn-affil= en-keyword=photonic crystal waveguides kn-keyword=photonic crystal waveguides en-keyword=potential sensors kn-keyword=potential sensors en-keyword=radiation-tolerant sensors kn-keyword=radiation-tolerant sensors en-keyword=space silicon photonics kn-keyword=space silicon photonics en-keyword=spacecrafts charging kn-keyword=spacecrafts charging 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=2025 dt-pub=20250305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Incidence and survival outcomes of myocarditis and pericardial diseases associated with immune checkpoint inhibitor therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Immune checkpoint inhibitor(ICI) induced cardiac immune related adverse events are challenging to study; Leveraging large data bases like TriNetX global health network may provide needed insights.
Methods We performed a retrospective cohort study including patients diagnosed neoplasm and 18 and older when receiving ICI therapy from 1/1/2011 to 12/31/2022. Queried ICD 9/10 codes identified patients experiencing myocarditis, pericarditis, pericardial effusion, and cardiac tamponade within 1 year of ICI initiation. Survival analyses compared one-year overall survival (OS) of patients experiencing cardiac irAEs against propensity score matched populations not experiencing them.
Results In 88,928 identified ICI patients, the incidence of myocarditis(0.48%), pericarditis(0.22%), and cardiac tamponade(0.47%) were less than 1% while pericardial effusion occurred in 4.71% of patients. Hazard ratios (HRs) were significantly higher in all cardiac irAE groups: myocarditis (HR:1.26, 95% CI:1.04?1.54, p?=?0.02), pericarditis (HR:1.36, 95% CI:1.02?1.82, p?=?0.04), pericardial effusion (HR:1.49, 95% CI:1.39?1.59, p? Discussion/conclusion Utilizing a uniquely large cohort of ICI patients, this study further shows the rarity of cardiac inflammatory irAEs and highlights their significant impact on patient survival. en-copyright= kn-copyright= 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=1 ORCID= en-aut-name=SayerMichael en-aut-sei=Sayer en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=NagasakaMisako en-aut-sei=Nagasaka en-aut-mei=Misako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LeeBenjamin J. en-aut-sei=Lee en-aut-mei=Benjamin J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DohJean en-aut-sei=Doh en-aut-mei=Jean kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaqviAli en-aut-sei=Naqvi en-aut-mei=Ali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NowrouziNareh en-aut-sei=Nowrouzi en-aut-mei=Nareh 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=PatelPranav M. en-aut-sei=Patel en-aut-mei=Pranav M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= affil-num=2 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= affil-num=3 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Hematology and Oncology, University of California kn-affil= affil-num=5 en-affil=Department of Pharmacy, University of California kn-affil= affil-num=6 en-affil=Department of Pharmacy, University of California kn-affil= affil-num=7 en-affil=Division of Cardiology, Department of Medicine, University of California kn-affil= affil-num=8 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= affil-num=9 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=10 en-affil=Division of Cardiology, Department of Medicine, University of California kn-affil= en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors en-keyword=Myocarditis kn-keyword=Myocarditis en-keyword=Cardiotoxicity kn-keyword=Cardiotoxicity en-keyword=Immune-related adverse events kn-keyword=Immune-related adverse events en-keyword=Overall survival kn-keyword=Overall survival END start-ver=1.4 cd-journal=joma no-vol=338 cd-vols= no-issue=16 article-no= start-page=1641 end-page=1650 dt-received= dt-revised= dt-accepted= dt-pub-year=2003 dt-pub=20030729 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Stereoselectivity in deoxygenation of 5-hydroxy-5-phosphinyl-hexofuranoses (α-hydroxyphosphonates) en-subtitle= kn-subtitle= en-abstract= kn-abstract=The addition of dimethyl phosphonate to six different hexofuranos-5-uloses in the presence of DBU, followed by esterification with methoxalyl chloride and then radical reduction, afforded 5-deoxy-5-dimethoxyphosphinyl-d- and l-hexofuranoses. The stereoselectivity of the deoxygenation and possible transition-state models are discussed. 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=SugiyamaKen-ichi en-aut-sei=Sugiyama en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawamotoHeizan en-aut-sei=Kawamoto en-aut-mei=Heizan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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= affil-num=4 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= en-keyword=Phospho sugar kn-keyword=Phospho sugar en-keyword=Deoxygenation kn-keyword=Deoxygenation en-keyword=α-Hydroxyphosphonate kn-keyword=α-Hydroxyphosphonate END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=1 article-no= start-page=251 end-page=261 dt-received= dt-revised= dt-accepted= dt-pub-year=2005 dt-pub=2005 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis of Phospholane 1-Oxide Having Oxygen Functional Groups from a 4-Bromobutylphoshinate Derivative en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ethyl 4-bromo-2,3-dimethoxybutyl(phenyl)phosphinate (10a) was prepared from 2,3-di-O-methyl-L-threitol (12) in five steps. Reduction of 10a with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by the action of hydrogen peroxide, afforded 3,4-dimethoxy-1-phenylphospholane 1-oxide (3), while the reaction of 10a with magnesium in boiling THF resulted in the formation of ethyl 2-methoxy-3-butenyl(phenyl)phosphinate (26). 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=KawaseShigeru en-aut-sei=Kawase en-aut-mei=Shigeru 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=67 cd-vols= no-issue=1 article-no= start-page=e15868 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 case of fetal myocardial calcification with hyperechoic area in fetal echocardiography en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SatoTakeshi en-aut-sei=Sato en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WashioYosuke en-aut-sei=Washio en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BabaKenji en-aut-sei=Baba en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EtoEriko en-aut-sei=Eto en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pediatrics, 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 Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=myocardial calcification kn-keyword=myocardial calcification END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=6 article-no= start-page=e70681 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bridging the Awareness?Action Gap in Disaster Preparedness: A Qualitative Study of Immersive Virtual Reality Learning Among Nursing Students en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Disasters increasingly challenge healthcare systems, highlighting the need to strengthen preparedness among future healthcare professionals. Although disaster risk awareness is important, it does not consistently translate into preparedness behaviours, reflecting the awareness?action gap. Immersive virtual reality (VR) may enhance experiential disaster learning, but how it influences preparedness processes remains insufficiently understood, particularly in healthcare and critical care education.
Aims: To explore how immersive VR-based disaster simulations influence disaster risk perception and preparedness among nursing students, with particular attention to the awareness?action gap and implications for future healthcare and critical care practice.
Study Design: A qualitative descriptive study using immersive VR-based disaster simulations followed by semi-structured interviews. Twelve undergraduate and graduate nursing students in Japan experienced immersive VR simulations depicting floods and landslides. Individual semi-structured interviews explored emotional responses, disaster risk perception, preparedness awareness and anticipated behavioural responses. Data were analysed using Krippendorff's content analysis with researcher triangulation.
Results: Five categories were identified: (1) heightened vulnerability and psychological burden through immersion; (2) persistence of the awareness?action gap despite increased risk perception; (3) enhanced risk recognition and preparedness intentions; (4) recognition of the need for social and structural support systems; and (5) emerging responsibility accompanied by perceived limitations. VR transformed abstract disaster risk into emotionally salient experiences, strengthening threat appraisal and preparedness awareness; however, awareness did not consistently translate into preparedness behaviours, reflecting insufficient coping appraisal and self-efficacy.
Conclusions: Immersive VR may strengthen disaster risk perception and preparedness awareness, but immersive experiences alone may be insufficient to bridge the awareness?action gap. Combining VR with reflective learning, skills-based training and collaborative simulation may strengthen coping appraisal and preparedness action.
Relevance to Clinical Practice: Immersive VR combined with reflective and skills-based learning may support psychological readiness, situational awareness and disaster preparedness competencies among future nurses, including those preparing for critical care practice. en-copyright= kn-copyright= en-aut-name=MoriKeiko en-aut-sei=Mori en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamazakiMiina en-aut-sei=Yamazaki en-aut-mei=Miina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HarunaYoshiyuki en-aut-sei=Haruna en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Kobe University Hospital kn-affil= affil-num=3 en-affil=Snowlion. Inc. kn-affil= en-keyword=awareness?action gap kn-keyword=awareness?action gap en-keyword=critical care nursing kn-keyword=critical care nursing en-keyword=disaster preparedness kn-keyword=disaster preparedness en-keyword=disaster risk perception kn-keyword=disaster risk perception en-keyword=nursing students kn-keyword=nursing students en-keyword=simulation-based education kn-keyword=simulation-based education en-keyword=virtual reality kn-keyword=virtual reality END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=18 article-no= start-page=8117 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260912 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Salivary miR-324-5p Is Associated with Periodontal Inflamed Surface Area in People Living with HIV Receiving Antiretroviral Therapy: A Case?Control Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontitis is a common inflammatory disease that affects the tooth-supporting tissues. Salivary microRNA (miRNA) expression in extracellular vesicles (EVs) can reflect periodontal status. Both the prevalence and severity of periodontitis are higher in people with human immunodeficiency virus (PWH). This study aimed to identify miRNA in salivary EVs associated with periodontitis in PWH receiving antiretroviral therapy (ART). The case group comprised PWH with periodontitis undergoing ART, while the control group included individuals with periodontitis but without HIV infection. The study was conducted in two phases. In the first phase, a specific miRNA was identified in the case group using next-generation sequencing analysis, resulting in the selection of hsa-miR-324-5p as a candidate marker of periodontitis. In the second phase, the association between miRNA expression of hsa-miR-324-5p and periodontal status in the case group was evaluated using real-time-quantitative PCR (RT-qPCR). RT-qPCR analysis demonstrated that hsa-miR-324-5p expression was significantly associated with periodontal inflamed surface area (PISA). Bioinformatic analysis identified 10 potential hub genes for hsa-miR-324-5p that are involved in protein kinase binding and are associated with the adherens junction pathway, that may be contributing to the pathogenesis of periodontitis. Salivary hsa-miR-324-5p derived from EVs may be associated with the severity of periodontitis among PWH receiving ART. en-copyright= kn-copyright= en-aut-name=NurhamimMohammad en-aut-sei=Nurhamim en-aut-mei=Mohammad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokoiAya en-aut-sei=Yokoi en-aut-mei=Aya 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=MaruyamaTakayuki en-aut-sei=Maruyama en-aut-mei=Takayuki 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, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=miR-324-5p kn-keyword=miR-324-5p en-keyword=saliva kn-keyword=saliva en-keyword=marker kn-keyword=marker en-keyword=HIV kn-keyword=HIV en-keyword=periodontitis kn-keyword=periodontitis en-keyword= extracellular vesicles kn-keyword= extracellular vesicles en-keyword=inflammation kn-keyword=inflammation END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=1 end-page=14 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260923 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Direct evidence for water-filled yet hydraulically isolated xylem vessels in two temperate tree species en-subtitle= kn-subtitle= en-abstract= kn-abstract=Xylem vessels in sapwood are typically interpreted as either conductive or non-functional following embolism or occlusion, implicitly assuming that the presence of water within the lumen reflects participation in the transpiration stream. However, the relationship between lumen water content and hydraulic connectivity has rarely been examined directly at the cellular level. In this study, we combined cryo-scanning electron microscopy and fluorescence microscopy to compare lumen water status with hydraulic connectivity on the same xylem surface in current-year xylem of Carpinus tschonoskii and Aria alnifolia, using tension-driven dye uptake to identify conductive vessels. Most vessels were stained and water-filled, consistent with functional conduits, whereas unstained gas-filled vessels corresponded to embolized conduits. Notably, certain vessels retained water despite lacking dye signals, indicating hydraulic isolation from the conductive xylem network. Although these vessels represented a minor fraction of the conduit population, their occurrence suggests that the traditionally binary classification should be expanded to incorporate an additional conduit function. These vessels were observed in both species, suggesting that hydraulically disconnected vessels represent a common phenomenon across species. These findings reveal previously underrecognized heterogeneity in xylem hydraulic organisation and demonstrate that conduit status cannot always be inferred from the presence of water alone. Recognising this intermediate condition refines current interpretations of xylem function and highlights the value of integrating high-resolution imaging with hydraulic measurements. en-copyright= kn-copyright= en-aut-name=OgasaMayumi?Y. en-aut-sei=Ogasa en-aut-mei=Mayumi?Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UtsumiYasuhiro en-aut-sei=Utsumi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YazakiKenichi en-aut-sei=Yazaki en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MikiNaoko?H. en-aut-sei=Miki en-aut-mei=Naoko?H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukudaKenji en-aut-sei=Fukuda en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Kansai Research Center, Forestry and Forest Products Research Institute kn-affil= affil-num=2 en-affil=Ashoro Research Forest, Kyushu University kn-affil= affil-num=3 en-affil=Hokkaido Research Center, Forestry and Forest Products Research Institute kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology kn-affil= affil-num=5 en-affil=Graduate School of Agricultural and Life Sciences, The University of Tokyo kn-affil= en-keyword= cryo-scanning electron microscopy kn-keyword= cryo-scanning electron microscopy en-keyword=fluorescence microscopy kn-keyword=fluorescence microscopy en-keyword=hydraulic isolation kn-keyword=hydraulic isolation en-keyword=vessel function kn-keyword=vessel function en-keyword=water distribution kn-keyword=water distribution END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=3 article-no= start-page=1 end-page=15 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250903 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Presentation Quality Assessment through Audience 3D Facial and Head Direction Using Conventional Cameras en-subtitle= kn-subtitle= en-abstract= kn-abstract=This paper shows the method for evaluating the quality of presentations using information from the audience's facial and head behavior. Existing studies have focused on assessing presentation skills by analyzing presentation materials and the presenter's verbal and non-verbal cues, however, since a presentation is an interaction between the presenter and the audience, the presentation quality is not only influenced by presenter's information but also audience's information such as their background knowledge. This means that the presenter's output alone is not enough for a comprehensive evaluation of the presentation. To address this, we show a method that utilizes videos of the audience recorded during presentations using two cameras: one capturing from the presenter's point of view and the other from around the presentation screen. The 3D position and direction of the audience's face were detected using face detection techniques, which were then used to predict gaze targets, such as the presenter and the presentation screen. The number of times these targets were looked at during the presentation served as feature values for evaluating presentation quality. Using a dataset of 18 presenters and 32 audience members, this paper shows a significant correlation between subjective ratings and behavioral characteristics. It also demonstrates an algorithm that infers the quality of a presentation from these feature values. en-copyright= kn-copyright= en-aut-name=ImamuraGoshi en-aut-sei=Imamura en-aut-mei=Goshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakazawaAtsushi en-aut-sei=Nakazawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Okayama University kn-affil= en-keyword=presentation quality kn-keyword=presentation quality en-keyword=computer vision kn-keyword=computer vision en-keyword=gaze kn-keyword=gaze END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=1 end-page=15 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=MIT/TFE family transcription factors, Mitf and Tfec, redundantly promote pigment cell differentiation and retinal epithelium pigmentation in teleosts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Transcription factors of the MIT/TFE family?mitfa, mitfb, and tfec?play essential roles in specifying pigment cells derived from neural crest cells in vertebrates. In teleosts, which possess multiple pigment cell types, these factors exhibit partially redundant but largely distinct functions across different pigment lineages. We previously reported that the combined loss of mitfa and mitfb leads to a complete absence of melanophores, xanthophores, and leucophores in medaka.
Results: Here, we describe newly generated hypomorphic alleles of mitfa and mitfb, which result in delayed melanophore development. Using these hypomorphic mutants in combination with a newly generated null allele of tfec, we show that Tfec can partially compensate for the loss of Mitfa and Mitfb in melanophore, xanthophore, and leucophore differentiation. Consistent with previous findings in zebrafish, loss of tfec alone results in the complete absence of iridophores. Importantly, simultaneous null mutations in all three genes cause a complete loss of all four chromatophore types and lead to defective pigmentation of the retinal pigmented epithelium (RPE), which is not derived from the neural crest in both Oryzias species and in zebrafish. Using an RPE-specific marker, we further show that the RPE is specified and structurally intact but fails to melanize.
Conclusions: These findings indicate that the redundant functions of Mitfa, Mitfb, and Tfec are not only essential for the specification of diverse pigment cell types but also critical for RPE pigmentation. en-copyright= kn-copyright= en-aut-name=ListerJames en-aut-sei=Lister en-aut-mei=James kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KimuraTetsuaki en-aut-sei=Kimura en-aut-mei=Tetsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaRieko en-aut-sei=Tanaka en-aut-mei=Rieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GodaMakoto en-aut-sei=Goda en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiHikaru en-aut-sei=Kobayashi en-aut-mei=Hikaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=InoueChikako en-aut-sei=Inoue en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= en-aut-name=NaruseKiyoshi en-aut-sei=Naruse en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=KelshRobert N. en-aut-sei=Kelsh en-aut-mei=Robert N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 ORCID= affil-num=1 en-affil=Department of Human and Molecular Genetics and Massey Cancer Center, Virginia Commonwealth University School of Medicine kn-affil= affil-num=2 en-affil=Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University kn-affil= affil-num=3 en-affil=Department of Basic Biology, School of Life Science, Graduate University of Advanced Studies (SOKENDAI) & Laboratory of Bioresources, National Institute for Basic Biology kn-affil= affil-num=4 en-affil=World Medaka Aquarium, Nagoya Higashiyama Zoo and Botanical Gardens kn-affil= affil-num=5 en-affil=Institute of Photonics Medicine, Hamamatsu University School of Medicine 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=R&D Fish Breeding Group, Regional Fish Institute, Ltd. kn-affil= affil-num=8 en-affil=Faculty of Fisheries and Marine Science, Sam Ratulangi University kn-affil= affil-num=9 en-affil=Tropical Biosphere Research Center, University of the Ryukyus kn-affil= affil-num=10 en-affil=Department of Basic Biology, School of Life Science, Graduate University of Advanced Studies (SOKENDAI) & Laboratory of Bioresources, National Institute for Basic Biology kn-affil= affil-num=11 en-affil=Ushimado Marine Institute, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=12 en-affil=Department of Life Sciences, University of Bath kn-affil= affil-num=13 en-affil=Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University kn-affil= affil-num=14 en-affil=Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University kn-affil= en-keyword=compound mutants kn-keyword=compound mutants en-keyword=melanization kn-keyword=melanization en-keyword=neural crest kn-keyword=neural crest en-keyword=retina kn-keyword=retina en-keyword=RPE kn-keyword=RPE END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=8 article-no= start-page=e106715 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=Study protocol for a phase II clinical trial evaluating the safety and efficacy of favipiravir injection combined with oseltamivir in influenza treatment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Older adults are at an increased risk of influenza-related hospitalisation and mortality due to a combination of risk factors. Severe influenza and excess mortality in this population remain major public health concerns, underscoring the need for novel treatment strategies.
Methods and analysis This multicentre, investigator-initiated, randomised, double-blind clinical trial evaluated the efficacy and safety of the investigational drug favipiravir injection (T-705IV) in combination with oseltamivir phosphate, compared with oseltamivir monotherapy in hospitalised patients with influenza aged ?65 years. Both T-705IV and oseltamivir phosphate will be administered for 5?days. The primary endpoint is time from randomisation to recovery within 15 days. Recovery is defined as either actual hospital discharge or sustained clinical status permitting discharge for 3 consecutive days. Clinical status will be assessed using a 7-point ordinal scale based on hospitalisation status and oxygen requirement. The primary analysis employs a Bayesian Cox proportional hazards model with a non-informative prior to estimate the posterior probability that the HR exceeds 1.0. The secondary endpoints include the distribution of 7-point scale scores over a 29-day period; rates of clinical worsening at days 15 and 29; duration of fever; all-cause mortality; intensive care unit admission within 29 days; pneumonia complication rate at 15 days; and changes in viral titre and viral RNA load on days 1, 2, 3 and 7. Safety will be assessed through the collection of adverse events (AEs) up to day 29. Pharmacokinetic evaluation will include measurement of plasma favipiravir concentrations on day 3. The planned sample size is 80 patients (40 per group).
Ethics and dissemination Written informed consent will be obtained from all participants. This study was approved by the Center Hospital of the National Center for Global Health and Medicine Institutional Review Board (approval number: NCGM-I-022-24a) and registered in the Japan Registry of Clinical Trials. Study findings will be disseminated through peer-reviewed publications and/or presentations at academic conferences.
Trial registration number jRCT2031240586, en-copyright= kn-copyright= en-aut-name=HikidaSayaka en-aut-sei=Hikida en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomotoHidetoshi en-aut-sei=Nomoto en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UemuraYukari en-aut-sei=Uemura en-aut-mei=Yukari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiTadaki en-aut-sei=Suzuki en-aut-mei=Tadaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 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=8 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=9 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=10 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=11 ORCID= en-aut-name=NukuiYoko en-aut-sei=Nukui en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoKazuko en-aut-sei=Yamamoto en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=SawadaKota en-aut-sei=Sawada en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimizuYosuke en-aut-sei=Shimizu en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MiyamotoSho en-aut-sei=Miyamoto en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TamuraNamiko en-aut-sei=Tamura en-aut-mei=Namiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TakahashiKozue en-aut-sei=Takahashi en-aut-mei=Kozue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SaitoSho en-aut-sei=Saito en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MiyazakiKazuki en-aut-sei=Miyazaki en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MorinoEriko en-aut-sei=Morino en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TokitaDaisuke en-aut-sei=Tokita en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 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=24 ORCID= affil-num=1 en-affil=Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security kn-affil= affil-num=2 en-affil=Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security kn-affil= affil-num=3 en-affil=Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=4 en-affil=Department of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=5 en-affil=Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=6 en-affil=Project Research Center for Nosocomial Infectious Diseases, Hiroshima University kn-affil= affil-num=7 en-affil=Infectious Diseases Center, Rinku General Medical Center kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, International University of Health and Welfare Narita Hospital kn-affil= affil-num=9 en-affil=Department of Infectious Diseases, Japanese Red Cross Narita Hospital kn-affil= affil-num=10 en-affil=Department of Clinical Microbiology and Infection, Tohoku University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Infection Control & Laboratory Medicine, Kyoto Prefectural University of Medicine kn-affil= affil-num=13 en-affil=First Department of Internal Medicine, Division of Infectious, Respiratory, and Digestive Medicine, University of the Ryukyus Graduate School of Medicine kn-affil= affil-num=14 en-affil=Chita Peninsula General Medical Organization, Rinku Hospital kn-affil= affil-num=15 en-affil=Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=16 en-affil=Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=17 en-affil=Department of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=18 en-affil=Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security kn-affil= affil-num=19 en-affil=Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security kn-affil= affil-num=20 en-affil=Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security kn-affil= affil-num=21 en-affil=Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=22 en-affil=Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=23 en-affil=Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=24 en-affil=Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security kn-affil= END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=9986 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260820 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=RNase-mediated defence and its association with SCCmec in Staphylococcus aureus en-subtitle= kn-subtitle= en-abstract= kn-abstract=The rise of antibiotic resistance in Staphylococcus aureus is a major threat to global health. Resistance often emerges when bacteria acquire foreign DNA elements, such as the SCCmec cassette that makes strains resistant to nearly all β-lactam antibiotics. Yet, not all S. aureus lineages take up these elements equally, raising the question of what prevents some strains from becoming drug-resistant. Here we identify a previously unknown defence factor that explains this mystery in a common skin lineage (ST188), frequently isolated from patients with atopic dermatitis. Such defence factor is encoded by a gene, which we name sadR, that is present in methicillin-susceptible ST188 strains but absent from resistant counterparts. SadR exhibits RNase activity that provides anti-bacteriophage and anti-plasmid defence, thus acting as a barrier to the uptake of mobile genetic elements. Gene sadR is found in methicillin-susceptible strains in S. aureus lineages other than ST188, and is consistently located adjacent to rlmH, the canonical SCCmec integration site. Moreover, SadR homologues are widespread across staphylococci and other bacteria suggesting a previously unrecognised family of RNase-based defence systems. en-copyright= kn-copyright= en-aut-name=KondoKohei en-aut-sei=Kondo en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AzamAa Haeruman en-aut-sei=Azam en-aut-mei=Aa Haeruman kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=OjimaShinjiro en-aut-sei=Ojima en-aut-mei=Shinjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChiharaKotaro en-aut-sei=Chihara en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraTomohiro en-aut-sei=Nakamura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TamuraAzumi en-aut-sei=Tamura en-aut-mei=Azumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamashitaWakana en-aut-sei=Yamashita en-aut-mei=Wakana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanoSatoshi en-aut-sei=Nakano en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=SugawaraYo en-aut-sei=Sugawara en-aut-mei=Yo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=AmagaiMasayuki en-aut-sei=Amagai en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamaguchiTetsuo en-aut-sei=Yamaguchi en-aut-mei=Tetsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IshiiYoshikazu en-aut-sei=Ishii en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=WatashiKoichi en-aut-sei=Watashi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakahashiYoshimasa en-aut-sei=Takahashi en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 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=19 ORCID= affil-num=1 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=2 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=3 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=4 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=5 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=6 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=7 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=8 en-affil=Department of Drug Development, 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=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=12 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Dermatology, Keio University School of Medicine kn-affil= affil-num=14 en-affil=Department of Microbiology and Infectious Diseases, Toho University School of Medicine kn-affil= affil-num=15 en-affil=Department of Microbiology and Infectious Diseases, Toho University School of Medicine kn-affil= affil-num=16 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=17 en-affil=Research Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=18 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=19 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security 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=20260921 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fatigue Life Evaluation Using the Damage‐Equivalent Strain for 7075‐T6 Aluminum Alloy Under Bending and Torsion Bending Vibrations en-subtitle= kn-subtitle= en-abstract= kn-abstract=The vibrations caused by external factors (such as fluids) or internal factors often pose strength-related problems in mechanical and structural components. Although several studies have investigated the material fatigue characteristics during vibration, reports on complex vibration modes such as torsion bending are limited. In this study, we addressed this gap by conducting experiments and finite element analyses on I- and L-shaped aluminum alloy specimens under bending and torsion bending vibrations, respectively. We established a reliable method to estimate the strain at the notch by utilizing the strain measured at a position outside the notch and a ratio derived from finite element analysis. This method allows for accurate assessment of the critical strain history without interfering with crack observation. Using the strain range at the crack initiation site effectively unified the fatigue life evaluation for both specimens. en-copyright= kn-copyright= en-aut-name=SakamotoJunji en-aut-sei=Sakamoto en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TadaNaoya en-aut-sei=Tada en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UemoriTakeshi en-aut-sei=Uemori en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Faculty 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=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=bending vibration kn-keyword=bending vibration en-keyword=crack propagation kn-keyword=crack propagation en-keyword=damage-equivalent strain kn-keyword=damage-equivalent strain en-keyword=resonance frequency reduction kn-keyword=resonance frequency reduction en-keyword=torsion bending vibration kn-keyword=torsion bending vibration en-keyword=vibration fatigue kn-keyword=vibration fatigue END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=2 article-no= start-page=143 end-page=150 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Variation in the Association between Frailty and Disability over 10 Years: A Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Although frailty is associated with disability, its long-term persistence and changes over time remain unclear. This study aimed to investigate the long-term association between frailty and the incidence of disability over a 10-year follow-up period, evaluating how this association changed over time. Methods: This cohort study was conducted in Okayama City, Japan. Community-dwelling older adults aged ?65 years were included. Frailty was assessed using the Kihon Checklist, and disability was defined as a new certification for long-term care insurance. The association between frailty and disability was examined across five time periods (years 1?2, 3?4, 5?6, 7?8, and 9?10) using a marginal structural model with inverse probability of treatment weighting and inverse probability of censoring weighting. Results: The final analysis included 45,291 participants, with 17.3% classified as frail. The adjusted odds ratios (ORs) for the association between frailty and the incidence of disability gradually decreased over time but remained throughout the 10-year follow-up period. The adjusted ORs and 95% confidence intervals were 2.90 (2.55?3.29) for years 1?2, 2.40 (2.09?2.75) for years 3?4, 2.03 (1.76?2.34) for years 5?6, 1.75 (1.52?2.01) for years 7?8, and 1.58 (1.38?1.82) for years 9?10. Conclusion: Frailty was consistently associated with the incidence of disability over a 10-year follow-up period, with a stronger association in the earlier years and a gradual decline over time. en-copyright= kn-copyright= en-aut-name=HagiyamaAkikazu en-aut-sei=Hagiyama en-aut-mei=Akikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 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=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Epidemiology, 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= en-keyword=Frailty kn-keyword=Frailty en-keyword=Persons with disabilities kn-keyword=Persons with disabilities en-keyword=Aged kn-keyword=Aged en-keyword=Longitudinal studies kn-keyword=Longitudinal studies END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=3 article-no= start-page=ofaf118 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Amikacin Liposome Inhalation Suspension and Amikacin Resistance Development in Patients With Refractory Mycobacterium avium Complex Pulmonary Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background. Amikacin liposome inhalation suspension (ALIS) is key for treating refractory Mycobacterium avium complex pulmonary disease (MAC-PD). However, microbiological efficacy by subtype remains unknown. The frequency and mechanism of amikacin (AMK) resistance during ALIS administration are also unclear.
Methods. We retrospectively analyzed data from refractory MAC-PD patients who received ALIS for at least 6 months as an adjunct to guideline-based therapy at the NHO Kinki Chuo Chest Medical Center. We investigated the efficacy of ALIS and analyzed gene expression and the frequency of AMK resistance.
Results. We enrolled 44 patients (median age, 72.0 years): 19 (43.2%) with the noncavitary nodular bronchiectatic (NC-NB) subtype and 25 (56.8%) with the cavitary subtype. Overall, sputum culture conversion was 56.8% (25/44): 84.2% (16/19) in the NC-NB subtype and 36.0% (9/25) in the cavitary subtype (P = .001). During intermittent dosing, conversion occurred in 50.0% (9/18). In patients with C-reactive protein (CRP) ?1?mg/dL, cavitary subtype, and clarithromycin (CLM) resistance, the risk ratio for persistently positive cultures was 10.81 (95% CI, 1.66?70.40) compared with those with CRP <1?mg/dL, NC-NB subtype, and CLM susceptibility. Of all participants, 15.9% (7/44) had isolates with AMK resistance (minimum inhibitory concentration ?128??g/mL), and of these 71.4% (5/7) had rrs mutations.
Conclusions. Regimens that included ALIS achieved higher culture conversion in NC-NB than cavitary MAC-PD cases. High CRP levels, cavitary disease, and CLM resistance predicted persistent culture positivity. AMK resistance acquired during ALIS administration may limit treatment options for refractory MAC-PD. en-copyright= kn-copyright= en-aut-name=KuraharaYu en-aut-sei=Kurahara en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaShiomi en-aut-sei=Yoshida en-aut-mei=Shiomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OsugiAsami en-aut-sei=Osugi en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaYuya en-aut-sei=Tanaka en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiTakehiko en-aut-sei=Kobayashi en-aut-mei=Takehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=KawasakiYohei en-aut-sei=Kawasaki en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MitaraiSatoshi en-aut-sei=Mitarai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsuyuguchiKazunari en-aut-sei=Tsuyuguchi en-aut-mei=Kazunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center kn-affil= affil-num=2 en-affil=Clinical Research Center, NHO Kinki Chuo Chest Medical Center , Osaka , kn-affil= affil-num=3 en-affil=Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=4 en-affil=Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center kn-affil= affil-num=5 en-affil=Clinical Research Center, NHO Kinki Chuo Chest Medical Center kn-affil= affil-num=6 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Biostatistics, Graduate School of Medicine, Saitama Medical University kn-affil= affil-num=8 en-affil=Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=9 en-affil=Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center kn-affil= en-keyword=amikacin liposome inhalation suspension kn-keyword=amikacin liposome inhalation suspension en-keyword=Mycobacterium avium complex kn-keyword=Mycobacterium avium complex en-keyword=noncavitary-nodular bronchiectatic kn-keyword=noncavitary-nodular bronchiectatic en-keyword=amikacin resistance kn-keyword=amikacin resistance en-keyword=rrs mutation kn-keyword=rrs mutation END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=6 article-no= start-page=e110118 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Routine Generative AI Use and Acceptance of Medical AI: A Cross-Sectional Survey of Healthcare Workers and the Public in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Acceptance of medical artificial intelligence (AI) is critical for successful implementation, yet its acceptance may vary by clinical application and stakeholder group. Whether routine use of generative AI (GAI) is associated with acceptance of medical AI remains unclear.
Methods
A cross-sectional web survey was conducted in Japan in November 2025 using web-panel convenience sampling from an online research panel. The small analytic sample comprised 200 participants aged 20-69 years, including 100 healthcare workers and 100 non-healthcare workers. GAI use was assessed using two five-point items (GAI use at work and in daily life) and dichotomized as at least monthly use in either daily life or work versus less than monthly use in both settings, based on prespecified criteria. Acceptance of medical AI was measured for five scenario-based applications - AI-assisted imaging interpretation, AI-based health risk prediction, AI-based treatment recommendations, AI-enabled triage guidance, and AI-assisted robotic surgery - using a four-point acceptability scale; responses were dichotomized as acceptable versus not acceptable. Calibration weights were constructed to approximate Japanese internet users by raking on sex-by-age group and household income, normalized to the analytic sample size, and truncated at prespecified bounds. Adjusted prevalence ratios (aPRs) were estimated using modified Poisson regression with robust standard errors, stratified by occupation; covariates were selected a priori using a modified disjunctive cause criterion. This study was exploratory; therefore, adjustments for multiple comparisons were not performed.
Results
Among healthcare workers, the lower-use group had a higher prevalence of non-acceptance of AI-based health risk prediction (aPR 6.980, 95% CI 1.412-34.506) and AI-based treatment recommendations (aPR 4.364, 95% CI 1.331-14.305), whereas estimates for imaging interpretation, triage guidance, and robotic surgery remained statistically uncertain. Among non-healthcare workers, the lower-use group had a higher prevalence of non-acceptance of AI-assisted imaging interpretation (aPR 13.906, 95% CI 1.624-119.052), AI-based health risk prediction (aPR 4.861, 95% CI 1.133-20.862), AI-based treatment recommendations (aPR 6.288, 95% CI 1.386-28.530), and AI-assisted robotic surgery (aPR 6.173, 95% CI 1.435-26.561); the adjusted estimate for AI-enabled triage guidance was not statistically supported (aPR 1.840, 95% CI 0.521-6.505). Several estimates had wide confidence intervals, indicating substantial imprecision.
Conclusions
In this small exploratory web-panel convenience sample, lower-frequency GAI use was associated with higher non-acceptance of several medical AI applications. Associations were observed across more applications among non-healthcare workers than among healthcare workers. Because the study was cross-sectional, used convenience sampling, and included imprecise estimates with wide confidence intervals, the findings should not be interpreted causally. Larger studies using longitudinal or interventional designs are needed to clarify temporality and mechanisms. en-copyright= kn-copyright= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Center for Innovative Clinical Medicine, Medical Development Field, Okayama University kn-affil= en-keyword=generative ai kn-keyword=generative ai en-keyword=healthcare workers kn-keyword=healthcare workers en-keyword=medical ai kn-keyword=medical ai en-keyword=non-healthcare workers kn-keyword=non-healthcare workers en-keyword=technology acceptance kn-keyword=technology acceptance en-keyword=web-based survey kn-keyword=web-based survey END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=60 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260920 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Carbon solubility and liquid?liquid immiscibility in Fe?C?S ternary system up to 6?GPa: implications for the core of small planetary bodies en-subtitle= kn-subtitle= en-abstract= kn-abstract=High-pressure, high-temperature experiments were conducted in a multi-anvil press using seven different starting compositions to investigate the phase relations of Fe?C?S liquids at pressures up to 6 GPa and temperatures up to 2000 K. Quenched samples revealed immiscible C-rich and S-rich metallic liquids at 2 and 4 GPa, manifesting as either large immiscible zones or emulsified smaller droplets. On the contrary, no immiscibility was observed at 5 or 6 GPa. At these higher pressures, the carbon solubility limit, significantly reduced by increasing sulfur content in the ternary liquid, prevents the formation of a liquid phase rich in both C and S. Our findings thus indicate that super-liquidus immiscibility in Fe-rich compositions does not occur at pressures above 5 GPa, due to the differential pressure dependence of C solubility and miscibility. The limited C solubility in S-rich liquids at higher pressures effectively suppresses immiscibility. Based on these results, terrestrial planetary bodies with fluid cores at pressures exceeding 5 GPa are unlikely to experience liquid?liquid immiscibility, even when both carbon and sulfur are abundant, as sulfur limits carbon solubility and promotes its exsolution. For the Moon, immiscibility-induced core stratification is not expected, though local emulsification could occur near the core?mantle boundary (CMB). In smaller bodies, a two-liquid Fe?C?S core may form at high temperatures, but progressive cooling may lead to graphite crystallization and the potential development of a graphitic crust. 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=MorardGuillaume en-aut-sei=Morard en-aut-mei=Guillaume kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ManthilakeGeeth en-aut-sei=Manthilake en-aut-mei=Geeth kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ParisiadesParaskevas en-aut-sei=Parisiades en-aut-mei=Paraskevas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YangJing en-aut-sei=Yang en-aut-mei=Jing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FeiYingwei en-aut-sei=Fei en-aut-mei=Yingwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Le GodecYann en-aut-sei=Le Godec en-aut-mei=Yann kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KondoNozomi en-aut-sei=Kondo en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=AntonangeliDaniele en-aut-sei=Antonangeli en-aut-mei=Daniele kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=UMR CNRS 7590, Institut de Min?ralogie, de Physique des Mat?riaux et de Cosmochimie, IMPMC, Mus?um National d’Histoire Naturelle, Sorbonne Universit? kn-affil= affil-num=3 en-affil=Laboratoire Magmas et Volcans, Universit? Clermont-Auvergne kn-affil= affil-num=4 en-affil=UMR CNRS 7590, Institut de Min?ralogie, de Physique des Mat?riaux et de Cosmochimie, IMPMC, Mus?um National d’Histoire Naturelle, Sorbonne Universit? kn-affil= affil-num=5 en-affil=Earth and Planets Laboratory, Carnegie Institution for Science kn-affil= affil-num=6 en-affil=Earth and Planets Laboratory, Carnegie Institution for Science kn-affil= affil-num=7 en-affil=UMR CNRS 7590, Institut de Min?ralogie, de Physique des Mat?riaux et de Cosmochimie, IMPMC, Mus?um National d’Histoire Naturelle, Sorbonne Universit? kn-affil= affil-num=8 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=9 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=10 en-affil=UMR CNRS 7590, Institut de Min?ralogie, de Physique des Mat?riaux et de Cosmochimie, IMPMC, Mus?um National d’Histoire Naturelle, Sorbonne Universit? kn-affil= en-keyword=Iron?carbon?sulfur liquids kn-keyword=Iron?carbon?sulfur liquids en-keyword=Miscibility kn-keyword=Miscibility en-keyword=High pressure and high temperature kn-keyword=High pressure and high temperature en-keyword=Planetary cores kn-keyword=Planetary cores END start-ver=1.4 cd-journal=joma no-vol=98 cd-vols= no-issue= article-no= start-page=107057 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2027 dt-pub=202701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Transcriptional remodeling of local thyroid hormone metabolism is associated with feather growth termination in chicken wing feathers en-subtitle= kn-subtitle= en-abstract= kn-abstract=Feather elongation is sustained by continuous cell proliferation within the feather follicle; however, the molecular mechanisms responsible for feather growth termination remain poorly understood. In this study, we investigated molecular changes associated with feather growth termination by comparing two chicken wing feather types with contrasting growth characteristics: primary wing feathers and primary coverts. Histological and bromodeoxyuridine incorporation analyses demonstrated that primary wing feathers remained in an active growth phase, whereas primary coverts exhibited pulp regression, reduced cell proliferation, and characteristics of growth termination. Gene expression analyses showed that primary coverts exhibited reduced expression of prolactin receptor (PRLR), type 2 iodothyronine deiodinase (DIO2), and insulin-like growth factor 2 (IGF2), together with marked induction of the thyroid hormone (TH)-inactivating enzyme type 3 iodothyronine deiodinase (DIO3). In contrast, primary wing feathers exhibited relatively higher expression of PRLR, DIO2, and IGF2 than primary coverts, while maintaining consistently low DIO3 expression. Reporter assays showed increased IGF2 promoter activity following triiodothyronine (T3) treatment in all three independent experiments, although the increase did not reach statistical significance. Thus, the reporter assay provides only tentative support for T3 responsiveness of the IGF2 promoter, consistent with our previous in vivo and primary-culture findings showing T3-dependent increases in IGF2 expression. These coordinated transcriptional changes are consistent with remodeling of local TH metabolism during the transition from active feather growth to growth termination. While local TH concentrations and direct deiodinase activities remain to be quantified, and the causal relationship between PRL/PRLR signaling and DIO3 induction remains unresolved, this study provides a molecular framework for understanding how local endocrine regulation translates systemic hormonal signals into feather type-specific growth responses during avian feather development. Graphical abstract en-copyright= kn-copyright= en-aut-name=ShinoharaMasamichi en-aut-sei=Shinohara en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NozawaYuri en-aut-sei=Nozawa en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukuchiHibiki en-aut-sei=Fukuchi en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakeuchiYu en-aut-sei=Takeuchi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AizawaSayaka en-aut-sei=Aizawa en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakeuchiSakae en-aut-sei=Takeuchi en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Feather growth termination kn-keyword=Feather growth termination en-keyword=Prolactin kn-keyword=Prolactin en-keyword=Thyroid hormone metabolism kn-keyword=Thyroid hormone metabolism en-keyword=DIO3 kn-keyword=DIO3 en-keyword=Chicken kn-keyword=Chicken END start-ver=1.4 cd-journal=joma no-vol=478 cd-vols= no-issue= article-no= start-page=117156 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Deep-blue solid-state emission from Ternaphthalene: Photophysical tuning via multi-chromophore architectures en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report the synthesis and photophysical characterization of a series of “all-naphthalene” multi-chromophore systems, ternaphthalenes (TNps), designed for efficient deep-blue solid-state emission. Unlike planar polycyclic aromatic hydrocarbons that suffer from aggregation-caused quenching (ACQ), the twisted molecular architecture of TNps effectively inhibits π-π stacking interactions. Consequently, several TNps exhibit crystallization-induced emission enhancement (CIEE) or retain high quantum yields (up to 0.94) in the solid state. Kinetic analysis revealed that this efficiency stems from the significant suppression of non-radiative rates (knr) due to the restricted intramolecular rotation in the rigid crystal lattice. Furthermore, a decisive topological effect on the radiative rate (kf) was demonstrated. The 1,4-, 1,5- and 2,6-linked isomers display allowed transitions with large oscillator strengths (f) and fast radiative rate (kf = ca. 5 × 108 s?1), whereas the 2,7-linked isomers exhibit forbidden-like character with prolonged lifetimes. A distinct linear correlation between the experimental and calculated values empirically supports the applicability of the Strickler-Berg relationship in both solution and solid states. These findings demonstrate that controlling the chromophore connectivity is a powerful strategy to tune excited-state dynamics for developing high-performance deep-blue organic emitters. en-copyright= kn-copyright= en-aut-name=YamajiMinoru en-aut-sei=Yamaji en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiKengo en-aut-sei=Suzuki en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkamotoHideki en-aut-sei=Okamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Division of Molecular Science, Graduate School of Science and Engineering, Gunma University kn-affil= affil-num=2 en-affil=Hamamatsu Photonics K.K. kn-affil= affil-num=3 en-affil=Department of Chemistry, Faculty of Environment, Life, Natural Sciences and Technology, Okayama University kn-affil= en-keyword=Deep-blue fluorescence kn-keyword=Deep-blue fluorescence en-keyword=Solid-state emission kn-keyword=Solid-state emission en-keyword=Multi-chromophore system kn-keyword=Multi-chromophore system en-keyword=Radiative rate kn-keyword=Radiative rate en-keyword=Density functional theory (DFT) kn-keyword=Density functional theory (DFT) en-keyword=Structure-property relationship kn-keyword=Structure-property relationship END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue= article-no= start-page=485 end-page=494 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202611 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enhancement of mechanical properties in a cast hypereutectic Al?Si alloy via rapid cooling in heated mold continuous casting en-subtitle= kn-subtitle= en-abstract= kn-abstract=To enhance mechanical properties in cast hypereutectic Al?Si alloys, Al?14.5Si samples were produced by the heated mold continuous casting (HMC). The HMC process was conducted under unidirectional solidification at cooling rates (CRs) ranging from 4.6 × 10?1 to 1.3 × 103 K/s, which were obtained by controlling the casting speed (CS). The microstructure basically consisted of α-Al dendrite, Al?Si eutectic and primary Si, while their area fractions (fα-Al, fe, and fp-Si) varied depending on the CR. At the low CR of 4.6 × 10?1 K/s, their area fractions were as follows: fα-Al = 0.2%, fe = 97.3%, and fp-Si = 2.5%, which is the typical microstructural morphology of a hypereutectic Al-Si alloy. In contrast, at the high CR of 1.3 × 103 K/s, those area fractions were altered to fα-Al = 32.3% and fe = 67.7%, while primary Si was strongly suppressed (fp-Si ? 0%) despite the hypereutectic Al?14.5Si alloy. Moreover, at the high CR, the aluminum matrix appears to exhibit a nearly uniform crystal orientation along <101>. These microstructural changes may be related not only to high CR but also the difference in growth kinetics between primary Si and α-Al dendrites. Accordingly, an apparent eutectic composition shifted from 12.6 to 19.7 wt% Si. The atypical microstructural formation led to a significant improvement in the tensile properties: the ultimate tensile strength of 400 MPa and fracture strain of 17%. These tensile properties are more than twice those of the conventional cast hypereutectic Al?14.5Si alloy. en-copyright= kn-copyright= en-aut-name=TakeuchiShuhei en-aut-sei=Takeuchi en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakagawaShota en-aut-sei=Nakagawa en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShinzatoYoshifumi en-aut-sei=Shinzato en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MinodaTadashi en-aut-sei=Minoda en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtsukaNaotaka en-aut-sei=Ohtsuka en-aut-mei=Naotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkayasuMitsuhiro en-aut-sei=Okayasu en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=UACJ Corporation kn-affil= affil-num=3 en-affil=UACJ Corporation kn-affil= affil-num=4 en-affil=UACJ Corporation kn-affil= affil-num=5 en-affil=UACJ Corporation kn-affil= affil-num=6 en-affil=Department of Mechanical and Systems Engineering, Okayama University kn-affil= en-keyword=Hypereutectic Al?Si alloy kn-keyword=Hypereutectic Al?Si alloy en-keyword=Heated mold continuous casting kn-keyword=Heated mold continuous casting en-keyword=Mechanical property kn-keyword=Mechanical property en-keyword=Microstructural characteristics kn-keyword=Microstructural characteristics en-keyword=Supercooling kn-keyword=Supercooling END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=1 article-no= start-page=100037 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=Older patients with LBCL show comparable outcomes to younger patients and product-specific profiles in CAR-T therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a key treatment option for patients with relapsed or refractory large B-cell lymphoma (LBCL). However, data on its effectiveness and safety in older populations remain limited, particularly in real-world clinical practice. Moreover, comparative outcomes among different CAR-T products across age groups have not yet been fully characterized. We conducted a nationwide retrospective cohort study using data from the Japanese Society for Transplantation and Cellular Therapy. A total of 908 patients who received CAR-T therapy between January 2019 and September 2024 were included. Patients were categorized as younger (aged <65 years) or older (aged ?65 years). Subgroup analyses were performed by CAR-T product (tisagenlecleucel [tisa-cel], lisocabtagene maraleucel [liso-cel], and axicabtagene ciloleucel [axi-cel]). In univariate analysis, 1-year overall survival (OS) and progression-free survival (PFS) were comparable between younger and older patients (OS, 69.4% vs 65.7% [P = .40]; PFS, 47.9% vs 54.1% [P = .17]). In multivariate analysis, age ?65 years showed no significant association with OS (hazard ratio, 0.88; 95% confidence interval, 0.65-1.21; P = .44). The incidence of immune effector cell?associated neurotoxicity syndrome was significantly higher in older patients (12.7% vs 7.0%; P = .005). Compared with tisa-cel, axi-cel and liso-cel were associated with superior PFS, predominantly in younger patients. Among older patients, axi-cel was associated with higher nonrelapse mortality rate than tisa-cel. CAR-T therapy is feasible and effective for older patients with LBCL. These findings support age-adapted treatment strategies that consider both the efficacy and toxicity of each product. en-copyright= kn-copyright= en-aut-name=ShibataSho en-aut-sei=Shibata en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AraiYasuyuki en-aut-sei=Arai en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KandaJunya en-aut-sei=Kanda en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KajiDaisuke en-aut-sei=Kaji en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MinakataDaisuke en-aut-sei=Minakata en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitawakiToshio en-aut-sei=Kitawaki en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimadaKazuyuki en-aut-sei=Shimada en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimoyamaTatsu en-aut-sei=Shimoyama en-aut-mei=Tatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshiharaSatoshi en-aut-sei=Yoshihara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MakitaShinichi en-aut-sei=Makita en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=YamamotoGo en-aut-sei=Yamamoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=NakashimaYasuhiro en-aut-sei=Nakashima en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YoshidaAkiyo en-aut-sei=Yoshida en-aut-mei=Akiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=UmezawaYoshihiro en-aut-sei=Umezawa en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KatoJun en-aut-sei=Kato en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KimHaryoon en-aut-sei=Kim en-aut-mei=Haryoon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KataokaKeisuke en-aut-sei=Kataoka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=GotoHideki en-aut-sei=Goto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Hematology, Kyoto University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology, Kyoto University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Kyoto University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Toranomon Hospital kn-affil= affil-num=5 en-affil=Division of Hematology, Department of Medicine, Jichi Medical University kn-affil= affil-num=6 en-affil=Department of Hematology, Kyoto University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Nagoya University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=9 en-affil=Department of Hematology, Hyogo Medical University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, National Cancer Center Hospital, Tokyo kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology, Toranomon Hospital kn-affil= affil-num=13 en-affil=Department of Hematology, Chiba University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology, Osaka Metropolitan University Hospital kn-affil= affil-num=15 en-affil=Division of Transfusion Medicine, Kanazawa University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology, Institute of Science Tokyo Hospital kn-affil= affil-num=17 en-affil=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=18 en-affil=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=19 en-affil=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=20 en-affil=Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital kn-affil= affil-num=21 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=22 en-affil=Department of Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=1868 cd-vols= no-issue=1 article-no= start-page=149607 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2027 dt-pub=202701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural and functional analysis of a photosystem II mutant PsbA3-S264V en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosystem II (PSII) catalyzes water oxidation and oxygen evolution by a light-induced electron transfer chain, leading to the generation of electrons, protons and dioxygen. D1-S264 is a residue located close to the QB-binding site, and mutation of this residue has been shown to bring significant effects on the electron transfer and oxygen-evolving activities. Here we analyzed the structure of a Thermosynechococcus elongatus mutant PsbA3-S264V by cryo-electron microscopy at 1.96 ? resolution, which showed significant changes in the structure surrounding the bicarbonate and QB-binding region. Due to change of Ser to Val, the hydrogen-bond between the QB carbonyl oxygen and S264 is altered, which changed the protonation pathway of QB from the original route of D1-H252 through D1-S264 to QB, to a new, longer and less efficient route of D1-H252 through D1-F265 to QB. Two residues, D1-E244 and D2-E242, changed their side chain orientations significantly. Among them, D2-E242 adopted two conformations, and both are largely deviated from the original structure. All these changes led to alterations in hydrogen-bonding networks of two channels, channel A and channel B, that connect the stromal surface to QB and may function to transport protons to protonate QB. Furthermore, isothermal titration calorimetry experiments showed a diminished 3-(3,4-dichlorophenyl)-1, 1-dimethylurea (DCMU) binding affinity of the mutated PSII, which may be explained by a structural rotation of D1-F255 in the mutant based on structural analysis of DCMU-bound PSII. These findings offer valuable insights into the functions of D1-S264 in QB protonation and function, as well as in the DCMU-binding. en-copyright= kn-copyright= en-aut-name=FanSongbo en-aut-sei=Fan en-aut-mei=Songbo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=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=TsaiPi-Cheng en-aut-sei=Tsai en-aut-mei=Pi-Cheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JiaAnqi en-aut-sei=Jia en-aut-mei=Anqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugiuraMiwa en-aut-sei=Sugiura en-aut-mei=Miwa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, 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, 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, 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, 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, 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, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Proteo-Science Research Center, Ehime University kn-affil= affil-num=8 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Photosystem II kn-keyword=Photosystem II en-keyword=PsbA3-S264V kn-keyword=PsbA3-S264V en-keyword=QB protonation kn-keyword=QB protonation en-keyword=DCMU-binding kn-keyword=DCMU-binding en-keyword=Thermosynechococcus elongatus kn-keyword=Thermosynechococcus elongatus END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=e70330 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=Transcystostomal Bladder Tumor Resection in a Transgender Man After Phalloplasty en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction
Phalloplasty in transgender men is frequently complicated by a neourethral stricture, precluding standard transurethral access for bladder tumor resection. We describe the first reported case of a transcystostomal bladder tumor resection in a transgender man after a radial forearm free flap (RFFF) phalloplasty.
Materials and Surgical Technique
A 65-year-old transgender man, 23?years after an RFFF phalloplasty, presented with gross hematuria and a 15-mm posterior bladder tumor. A 7.95?Fr flexible ureteroscope reached the bladder but with markedly limited maneuverability. A two-stage transcystostomal approach was used: a 14?Fr suprapubic cystostomy (SPC) was placed 1?month before resection for tract maturation, followed by balloon dilation and insertion of a 24?Fr resectoscope. The modified Valdivia position enabled simultaneous transcystostomal and transurethral access with gravity-assisted irrigation drainage. Complete tumor resection was achieved without complications, and pathology confirmed noninvasive papillary urothelial carcinoma (pTa, low-grade) with negative margins. A single immediate intravesical instillation of pirarubicin was administered. Surveillance cystoscopy via the cystostomy tract at 3 and 6?months revealed no recurrence; the patient continues to void while standing with the cystostomy catheter capped.
Discussion
The two-stage transcystostomal approach, combining prior SPC placement, balloon tract dilation, and the modified Valdivia position, enabled safe oncological control while preserving phallic anatomy and standing voiding function. This technique offers a reproducible option for bladder tumor resection in patients with functionally inadequate transurethral access after phalloplasty. 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=OzakiNariaki en-aut-sei=Ozaki en-aut-mei=Nariaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoYuko en-aut-sei=Matsumoto en-aut-mei=Yuko 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=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=NambaYuzaburo en-aut-sei=Namba en-aut-mei=Yuzaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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, Miyakekai Good Life Hospital 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, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Gender Center, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=bladder neoplasms kn-keyword=bladder neoplasms en-keyword=gender-affirming surgery kn-keyword=gender-affirming surgery en-keyword=phalloplasty kn-keyword=phalloplasty en-keyword=suprapubic cystostomy kn-keyword=suprapubic cystostomy en-keyword=transgender persons kn-keyword=transgender persons END start-ver=1.4 cd-journal=joma no-vol=34 cd-vols= no-issue=2 article-no= start-page=118 end-page=129 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Factors promoting students’ application of health checkup reports: analysis using health literacy skills framework kn-title=中・高・大学生の健診結果活用の促進要因?ヘルスリテラシースキルフレームワークを用いた検討? en-subtitle= kn-subtitle= en-abstract=Objective: This study aimed to clarify the factors associated with the application of health checkup reports and their interrelationships using a health literacy skills framework.
Methods: An anonymous, self-administered questionnaire survey was administered 493 middle school, 360 high school and 297 first-year university students. The contents included “Application of Health Checkup Reports,” “Health Interest,” “Health Literacy (HL),” “Readability of The Health Checkup Report,” “Reading Comprehension of The Report,” and “Decision-making Balance.” The hypothetical model was tested using a multi group simultaneous path analysis by school type and sex.
Results: The revised model, in which four additional paths were added, showed a good fit across all school types and sex. The paths from “Readability” to “Reading comprehension,” “Reading comprehension” to “Decision-making,” “Decision-making” to “Application,” “Health Interest” to “Reading comprehension,” “Decision-making,” and “Application,” “HL” to “Application” were significant across all school types. Conversely, the paths from “Health Interest” and “Readability” to “HL,” and “HL” to “Reading comprehension” and “Decision-making,” were significant only among middle and high school students.
Conclusion: Making the results easier to understand, enhancing reading comprehension and recognition of the pros of health checkups, and reducing recognition of the cons might effectively promote the application of health checkup reports among students. kn-abstract=目的：学校健康診断結果活用（以下，活用）と関連要因及び相互の関連性をヘルスリテラシースキルフレームワークを用いて明らかにすることを目的とした．
方法：中学生493名，高校生360名，大学1年生297名を対象に無記名自記式質問紙調査を行った．調査内容は活用と，健康への関心，ヘルスリテラシー（以下，HL），健診結果に対する認識，健診結果の読解力（以下，読解力），意思決定バランスとした．これらの関連性を示す仮説モデルを校種，性別の多母集団同時パス解析で検証した．
結果：仮説モデルに4つのパスを追加した修正モデルで，校種，性別いずれにおいても配置不変モデルで良好な適合度を得た．健診結果に対する認識から読解力，読解力から意思決定バランス，意思決定バランスから活用，健康への関心から読解力，意思決定バランス，活用へのパス及び，HLから活用へのパスは全ての校種において有意であった．健康への関心と結果に対する認識からHL，HLから読解力，意思決定バランスへのパスは中・高校生のみで有意であった．
結論：中・高・大学生の健診結果活用を促すためには，健診結果を分かりやすくすること，健診結果の読解力及び意思決定バランスの向上，すなわち恩恵の認識の向上と，負担の認識の軽減が有効であり，その際に対象者の健康への関心とHLの程度を考慮する必要性が示唆された． en-copyright= kn-copyright= en-aut-name=ONISHIHitomi en-aut-sei=ONISHI en-aut-mei=Hitomi kn-aut-name=大西瞳 kn-aut-sei=大西 kn-aut-mei=瞳 aut-affil-num=1 ORCID= en-aut-name=NISHIOKANobuki en-aut-sei=NISHIOKA en-aut-mei=Nobuki kn-aut-name=西岡伸紀 kn-aut-sei=西岡 kn-aut-mei=伸紀 aut-affil-num=2 ORCID= en-aut-name=ITOTakehiko en-aut-sei=ITO en-aut-mei=Takehiko kn-aut-name=伊藤武彦 kn-aut-sei=伊藤 kn-aut-mei=武彦 aut-affil-num=3 ORCID= affil-num=1 en-affil=The Joint Graduate School (Ph.D. Program) in Science of School Education, Hyogo University of Teacher Education kn-affil=兵庫教育大学大学院連合学校教育学研究科 affil-num=2 en-affil=Faculty of Psychology and Collaboration, Kyoto Women’s University kn-affil=京都女子大学心理共生学部 affil-num=3 en-affil=Graduate School of Education, Okayama University kn-affil=岡山大学大学院教育学研究科 en-keyword=読みやすさ (readability) kn-keyword=読みやすさ (readability) en-keyword=読解力 (reading comprehension) kn-keyword=読解力 (reading comprehension) en-keyword=意思決定バランス (decision balance) kn-keyword=意思決定バランス (decision balance) en-keyword=健康への関心 (health interest) kn-keyword=健康への関心 (health interest) en-keyword=ヘルスリテラシー (health literacy) kn-keyword=ヘルスリテラシー (health literacy) END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=4 article-no= start-page=e70206 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Varicocelectomy Restores Spermatogenesis in Fontan‐Associated Varicocele: A Two‐Case Series en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Fontan circulation may cause chronic venous hypertension and predispose patients to varicocele and infertility,but the clinical significance of surgical treatment remains unclear.
Case Presentation: We describe two patients with Fontan circulation who developed Fontan-associated varicocele (FAVC). A42-year-old man presented with secondary infertility, bilateral varicocele, and progression to azoospermia after Fontan surgery.A 28-year-old man had asthenozoospermia, bilateral varicocele, and repeated failure of assisted reproductive technology. Bothunderwent bilateral microsurgical varicocelectomy with perioperative heparin bridging. Postoperative semen parameters im-proved in both patients, with sperm reappearing in the first case.
Conclusion: Varicocelectomy for FAVC may restore spermatogenesis in selected cases, but the risk of postoperative recurrencemay be increased. en-copyright= kn-copyright= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=MatsumotoYuko en-aut-sei=Matsumoto en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriwakeTakatoshi en-aut-sei=Moriwake en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OzakiNariaki en-aut-sei=Ozaki en-aut-mei=Nariaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=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, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Fontan circulation kn-keyword=Fontan circulation en-keyword=male infertility kn-keyword=male infertility en-keyword=spermatogenesis kn-keyword=spermatogenesis en-keyword=varicocele kn-keyword=varicocele en-keyword=varicocelectomy kn-keyword=varicocelectomy END start-ver=1.4 cd-journal=joma no-vol=49 cd-vols= no-issue=6 article-no= start-page=983 end-page=988 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260620 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of Deuterated Drugs on Safety: Insights from Pharmacovigilance Data Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Tetrabenazine (TBZ), a vesicular monoamine transporter 2 inhibitor, is commonly used to manage chorea; however, it may exhibit fluctuating plasma levels and elicit frequent adverse events. In this study, we aimed to clarify the effects of TBZ deuteration on its safety profile. We compared the safety profiles of TBZ and deutetrabenazine (DTBZ) in real-world clinical practice using disproportionality analysis and the large-scale pharmacovigilance database, VigiBase?the WHO’s global database of adverse drug reactions. Adverse event signals were assessed using the information component (IC). Seriousness was classified according to clinical outcome, and time to onset (TTO) was analyzed for selected events. TBZ showed signals for disorientation, dystonia, and sleep disorders (IC025 > 0), whereas DTBZ did not. Serious adverse events were reported in 54.7% of TBZ cases and 37.9% of DTBZ cases. The TTO of sleep disorder was also evaluated; however, the number of cases with available TTO information was limited. DTBZ showed fewer adverse event signals and a lower proportion of serious adverse events than TBZ. These findings suggest potential differences in the safety profiles of the two drugs, which may influence tolerability in the treatment of HD. en-copyright= kn-copyright= en-aut-name=KitagawaKohei en-aut-sei=Kitagawa en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NawaHideki en-aut-sei=Nawa en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsaiShota en-aut-sei=Asai en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=7 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=8 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=9 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama Psychiatric Medical Center kn-affil= affil-num=2 en-affil=Department of Pharmacy, Faculty of Pharmacy, Shujitsu University kn-affil= affil-num=3 en-affil=Department of Pharmacy, Faculty of Pharmacy, Shujitsu University 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, Tokushima University Graduate School of Biomedical Sciences 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, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=8 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences kn-affil= en-keyword=deuterated drug kn-keyword=deuterated drug en-keyword=VigiBase kn-keyword=VigiBase en-keyword=heavy drug kn-keyword=heavy drug en-keyword=safety advantage kn-keyword=safety advantage en-keyword=pharmacovigilance analysis kn-keyword=pharmacovigilance analysis END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=cr.26-0206 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=Single-Incision Laparoscopic Hartmann’s Reversal Using the Stoma Site in a Patient with Perioperative Anaphylaxis en-subtitle= kn-subtitle= en-abstract= kn-abstract=INTRODUCTION: Reversal of Hartmann’s procedure is associated with substantial morbidity, and further reduction of surgical invasiveness may be beneficial in selected patients. Perioperative anaphylaxis caused by anesthetic agents or skin antiseptics poses a significant challenge to surgical management. We report a case of stoma-site single-incision laparoscopic Hartmann’s reversal (HR) performed in a patient with severe perioperative allergies.
CASE PRESENTATION: A 73-year-old woman underwent an emergency open Hartmann’s procedure with partial cystectomy for perforated sigmoid colon cancer with bladder invasion. After adjuvant chemotherapy, she developed a progressively enlarging giant parastomal hernia that significantly impaired daily activities. Two attempts at HR were aborted because of perioperative anaphylactic shock. Subsequent allergy evaluations suggested rocuronium and chlorhexidine as causative agents, and povidone-iodine was also avoided based on clinical history. Approximately 14 months after the initial surgery, single-incision laparoscopic HR using the stoma site was successfully performed under general anesthesia without neuromuscular blocking agents. Preoperative skin antisepsis was performed using benzalkonium chloride, avoiding both chlorhexidine and povidone-iodine. No additional abdominal incisions were required. The operative time was 2 h 56 min, with minimal blood loss. The postoperative course was uneventful and she was discharged on POD 9.
CONCLUSIONS: Stoma-site single-incision laparoscopic HR may represent a useful surgical option for selected patients with severe perioperative allergies to anesthetic agents and skin antiseptics, in whom minimizing abdominal approach and wound-related risks is particularly important. en-copyright= kn-copyright= en-aut-name=YanagiharaTsubasa en-aut-sei=Yanagihara en-aut-mei=Tsubasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=YoshidaYusuke en-aut-sei=Yoshida en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=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=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KondoYoshitaka en-aut-sei=Kondo en-aut-mei=Yoshitaka 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, Okayama, Okayama, Japan 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=Hartmann’s reversal kn-keyword=Hartmann’s reversal en-keyword=single-incision laparoscopic surgery kn-keyword=single-incision laparoscopic surgery en-keyword=parastomal hernia kn-keyword=parastomal hernia en-keyword=perioperative anaphylaxis kn-keyword=perioperative anaphylaxis en-keyword=chlorhexidine allergy kn-keyword=chlorhexidine allergy END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=8 article-no= start-page=e00484-26 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260804 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High-throughput screening system for antimycobacterial compounds using in vitro infected cells: construction and application to compounds in the ?mura Natural Compound Library en-subtitle= kn-subtitle= en-abstract= kn-abstract=The global increase in multidrug-resistant tuberculosis strains poses a major threat; consequently, there is an urgent need to identify and develop novel drugs. We have previously presented a simple fibroblast assay (SFA) screening method that enables the simultaneous assessment of antibacterial activity and cytotoxicity toward host cells. This method was developed based on our finding that live (but not dead) Mycobacterium tuberculosis bacilli exhibit cytotoxic activity against human lung fibroblasts, and that this cytotoxicity, which is proportional to the number of viable bacterial cells, is inhibited by known antimycobacterial drugs. While conventional methods to measure M. tuberculosis growth require 2?4 weeks to detect antibacterial activity; the SFA method enables detection within 2?3 days and can detect compounds that are active within host cells. Here, we applied high-throughput screening, based on assessment of cytotoxicity, to identify candidate antimycobacterial agents. In parallel, by comparing the direct antibacterial activity of compounds in liquid medium (using the broth dilution test) with that observed via SFA, we developed a new SFA-based screening system to select compounds with low cytotoxicity that are active outside or inside the host cells. Using this dual system, we screened 742 compounds from the ?mura Natural Compound Library (Kitasato University, Japan), with 62 hits. Of these, 19 were excluded owing to their toxicity, and six exhibited antibacterial activity only via SFA screening. Four promising antimycobacterial candidates with no cytotoxicity at the 10 μg/mL threshold?aridicin A, lankamycin, streptovaricin, and lariatin A?were identified. identified.This novel system supports the rapid identification of low-cytotoxicity antimycobacterial compounds that are active inside or outside the host cells. en-copyright= kn-copyright= en-aut-name=TakiiTakemasa en-aut-sei=Takii en-aut-mei=Takemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimishimaAoi en-aut-sei=Kimishima en-aut-mei=Aoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IwatsukiMasato en-aut-sei=Iwatsuki en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeYoshihiro en-aut-sei=Watanabe en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=AsamiYukihiro en-aut-sei=Asami en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Mycobacterium Reference and Research, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=2 en-affil=?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=3 en-affil=?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=4 en-affil=?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=5 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=?mura Satoshi Memorial Institute, Kitasato University kn-affil= en-keyword=Mycobacterium tuberculosis kn-keyword=Mycobacterium tuberculosis en-keyword=Mycobacterium avium kn-keyword=Mycobacterium avium en-keyword=Mycobacterium abscessus kn-keyword=Mycobacterium abscessus en-keyword=fibroblasts kn-keyword=fibroblasts en-keyword=the ?mura Natural Compound Library kn-keyword=the ?mura Natural Compound Library en-keyword=antibacterial activity kn-keyword=antibacterial activity END start-ver=1.4 cd-journal=joma no-vol=2026 cd-vols= no-issue=1 article-no= start-page=1926696 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=Phenotypic Characterization of Porphyromonas gulae Fimbria Mutants en-subtitle= kn-subtitle= en-abstract= kn-abstract=Porphyromonas gulae has been established as a pathogen in animal periodontal disease and expresses several virulence factors, including fimbriae, lipopolysaccharide, and proteases. P. gulae fimbriae are classified into three genotypes (A, B, and C) based on the fimbrillin (fimA) gene encoding a fimbrial subunit protein. We previously reported that P. gulae organisms with type C fimbriae were clearly more virulent as compared to those with other fimbria types, though the basic function of this is not fully understood. Here, we investigated the function of fimbriae using fimA-deficient mutants. In the present study, bacterial fimbriae were related to biofilm tenacity, whereas biofilm formation was not. Also, P. gulae fimbriae are involved in bacterial adhesion and entry into gingival epithelial cells. The role of P. gulae fimbriae in bacterial pathogenicity was then determined using fimA-deficient mutants with a silkworm infection model. Additionally, P. gulae infection can induce inflammatory responses in gingival epithelial cells and also inhibit cell migration and proliferation. In contrast, a P. gulae fimA-deficient mutant did not cause several of those cellular responses. Together, the results show that fimbriae contribute to the pathogenicity of P. gulae by affecting bacterial functions and host cell interactions. en-copyright= kn-copyright= en-aut-name=InabaHiroaki en-aut-sei=Inaba en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaSho en-aut-sei=Yoshida en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=5 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=6 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 Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=5 en-affil=Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka kn-affil= affil-num=6 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=biofilm kn-keyword=biofilm en-keyword=cell invasion kn-keyword=cell invasion en-keyword=cell migration kn-keyword=cell migration en-keyword=fimbriae kn-keyword=fimbriae en-keyword=periodontitis kn-keyword=periodontitis en-keyword=Porphyromonas gulae kn-keyword=Porphyromonas gulae en-keyword=silkworm larvae kn-keyword=silkworm larvae END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=cr.26-0502 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=Successful Lung Transplantation after Plasma Exchange in a Patient with High Thermal Amplitude Cold Agglutinins: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=INTRODUCTION: Cold agglutinins (CAs) are immunoglobulin M autoantibodies that induce red blood cell agglutination at low temperatures and may cause hemolytic or thrombotic complications during procedures associated with hypothermia. In lung transplantation (LT), blood may be exposed to low temperatures within the reperfused lung graft and the extracorporeal circulation circuit, potentially increasing the risk of CA-mediated complications. However, the perioperative significance of CAs in this setting remains unclear, and optimal management has not been established. We report a case of successful bilateral LT in a patient with high-thermal-amplitude CAs managed with preoperative plasma exchange (PLEX) and strict intraoperative temperature control.
CASE PRESENTATION: A 55-year-old man with diffuse panbronchiolitis and secondary pulmonary hypertension was listed for bilateral LT. Preoperative testing incidentally revealed clinically significant CAs, with a titer of 1:128 at 4°C and a thermal amplitude of 30°C. Because intraoperative blood temperature might approach this threshold despite active warming, a single preoperative session of PLEX using 36 units of fresh frozen plasma was performed to reduce the risk of a CA-mediated complication. Bilateral LT was subsequently completed under meticulous temperature management, including extracorporeal circulation maintained at 37.5°C, continuous systematic warming, avoidance of topical ice application, and rewarming of the donor lungs before reperfusion. After surgery, the CA titer decreased to 1:32. The postoperative course was uneventful, without thromboembolic events, primary graft dysfunction, or bronchial complications.
CONCLUSIONS: LT may be performed safely in selected patients with high-thermal-amplitude CAs when careful perioperative temperature control is combined with preoperative PLEX. PLEX should be considered when the anticipated intraoperative temperature is expected to approach the patient’s thermal amplitude threshold. en-copyright= kn-copyright= en-aut-name=MiyoshiYuya en-aut-sei=Miyoshi en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsanoNaomi en-aut-sei=Asano en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoHaruchika en-aut-sei=Yamamoto en-aut-mei=Haruchika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkaharaShuji en-aut-sei=Okahara en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro 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= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Transfusion and Cell Therapy, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery, Okayama University Hospital, Okayama, Okayama, Japan kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Division of Transfusion and Cell Therapy, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=cold agglutinins kn-keyword=cold agglutinins en-keyword=thermal amplitude kn-keyword=thermal amplitude en-keyword= lung transplantation kn-keyword= lung transplantation en-keyword=plasma exchange kn-keyword=plasma exchange en-keyword=extracorporeal circulation kn-keyword=extracorporeal circulation en-keyword=perioperative management kn-keyword=perioperative management END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue= article-no= start-page=112872 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prediction of tool-path and cycle time errors of CNC machining using a transformer-based deep learning model en-subtitle= kn-subtitle= en-abstract= kn-abstract=The prediction of tool-path and cycle time errors of computer numerical control (CNC) machining is important in manufacturing field. In this study, these errors are considered as sequential data corresponding to the lines of G-code, i.e., the error prediction is a sequence-to-sequence task, and a Transformer-based deep learning model was constructed to predict the tool-path and cycle time errors simultaneously, taking the positional increments and feed rate as the input. The training datasets were created by running a randomly generated G-code on a real CNC machine tool and subsequently tracking the actual errors, where the motion and feed rate are stochastically defined. The model is validated by conducting the error prediction on six sets of G-code. In addition, the comparison with a Bi-LSTM-based deep learning model is conducted. The results show that the prediction accuracy of the Transformer model can achieve the mean prediction accuracies of ±1 μm and ±1 ms in tool-path and cycle time error predictions, respectively. Furthermore, the Transformer model has a smaller prediction uncertainty than the Bi-LSTM model. Compared with conventional methods only analyzing tool-path errors or cycle-time errors, the utilized model has an advantage in its ability to simultaneously predict tool-path errors and cycle time errors. en-copyright= kn-copyright= en-aut-name=KanekoKazuki en-aut-sei=Kaneko en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiZongze en-aut-sei=Li en-aut-mei=Zongze 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 Tech, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Advanced Science and Engineering, Hiroshima University kn-affil= en-keyword=CNC machining kn-keyword=CNC machining en-keyword=Tool-path error kn-keyword=Tool-path error en-keyword=Cycle time error kn-keyword=Cycle time error en-keyword=Deep learning kn-keyword=Deep learning en-keyword=Transformer kn-keyword=Transformer END start-ver=1.4 cd-journal=joma no-vol=757 cd-vols= no-issue= article-no= start-page=125992 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multi-criteria evaluation of graphene oxide nanofiltration membranes for decaffeination en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nanofiltration (NF) offers a promising low-energy approach for producing decaffeinated instant coffee, while requires membranes that balance caffeine removal, water permeance, and retention of key coffee matrix compounds. Here, graphene oxide membranes (GOMs) were modified by sodium alginate (SA) intercalation, Ca2+ crosslinking, and their combined strategy to tune nanochannel structure and separation performance. The results show that membrane modification does not follow a simple monotonic trend; instead, small structural and chemical changes generate competing effects on permeance and selectivity through coupled transport, adsorption, and confinement mechanisms. To identify the most suitable membrane, a multi-criteria evaluation framework (MCEF) combining entropy weighting and TOPSIS was established using five key performance indicators: caffeine removal, flavour-related marker retention index, choline retention, water permeance, and concentration increase. This framework identified CGSM-1 as the best-performing flat membrane, which also showed promising performance in hollow-fibre form. In coffee filtration tests, CGSM-1 reduced caffeine concentration from 24.64 to 12.95?μg/mg, corresponding to a 47.4% reduction, while retaining measurable levels of HMF, trigonelline, NMP, and choline. These findings demonstrate the potential of engineered GOMs for selective caffeine reduction in coffee liquor and provide a practical evaluation strategy for membrane-based decaffeination. en-copyright= kn-copyright= en-aut-name=TianYihan en-aut-sei=Tian en-aut-mei=Yihan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LinTongxi en-aut-sei=Lin en-aut-mei=Tongxi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=RenXiaojun en-aut-sei=Ren en-aut-mei=Xiaojun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=JoshiRakesh en-aut-sei=Joshi en-aut-mei=Rakesh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=School of Materials Science and Engineering, University of New South Wales kn-affil= affil-num=2 en-affil=School of Materials Science and Engineering, University of New South Wales kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=School of Materials Science and Engineering, University of New South Wales kn-affil= affil-num=5 en-affil=School of Materials Science and Engineering, University of New South Wales kn-affil= en-keyword=Multi-criteria evaluation kn-keyword=Multi-criteria evaluation en-keyword=Decaffeination kn-keyword=Decaffeination en-keyword=Graphene oxide kn-keyword=Graphene oxide END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=3 article-no= start-page=e0910 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260226 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hepatocellular carcinoma in Fontan-associated liver disease: Incidence, risk stratification, and surveillance implications en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Hepatocellular carcinoma (HCC) is a serious complication of Fontan-associated liver disease (FALD). However, data on its incidence, risk factors, and outcomes in this rare population are limited. We aimed to assess the incidence and predictors of HCC and evaluate the utility of surveillance in patients with FALD.
Methods: We conducted a retrospective cohort study on patients with FALD who were referred to our gastroenterology department. The cumulative incidence of HCC after FALD diagnosis was calculated, and multivariate analysis was used to identify independent risk factors. Overall survival after FALD diagnosis was compared between patients who developed HCC and those who did not.
Results: A total of 120 patients with FALD were followed up for a median period of 50.0 months. The cumulative incidence rates of HCC at 1, 2, and 3 years after FALD diagnosis were 0.9%, 2.7%, and 3.9%, respectively. Elevated alpha-fetoprotein (AFP) at FALD diagnosis was independently associated with HCC development (hazard ratio, 1.29; 95% confidence interval, 1.04?1.60; p=0.01). There was no significant difference in overall survival between patients with and without HCC in this cohort (log-rank test, p=0.50).
Conclusions: Patients with FALD face a non-negligible risk of developing HCC, thus supporting the need for surveillance. Elevated AFP levels at the time of FALD diagnosis may aid in risk stratification, which enables the targeted monitoring and early detection of HCC. Furthermore, routine surveillance contributes to the excellent prognosis of patients with FALD who develop HCC, thus making their prognosis comparable to that of patients without HCC. en-copyright= kn-copyright= en-aut-name=OnishiHideki en-aut-sei=Onishi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=BabaKenji en-aut-sei=Baba en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=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, Medical Development Field, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Medical Development Field, Okayama University, Okayama, Japan kn-affil= affil-num=3 en-affil=Department of Pediatric Cardiology, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Surgery, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Surgery, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=alpha-fetoprotein kn-keyword=alpha-fetoprotein en-keyword=FALD kn-keyword=FALD en-keyword=Fontan procedure kn-keyword=Fontan procedure en-keyword=retrospective cohort study kn-keyword=retrospective cohort study en-keyword=risk stratification kn-keyword=risk stratification END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=3 article-no= start-page=e044756 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=Long‐Term Outcomes and Risk Factors for Mortality After Single Ventricle Palliation for Asplenia Syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: This study evaluated the long‐term outcomes of asplenia syndrome with single ventricle palliation, hypothesizing that total anomalous pulmonary vein connection (TAPVC), pulmonary atresia (PA), and greater than or equal to moderate atrioventricular valve regurgitation increase mortality risk.
Methods: This retrospective review analyzed 151 patients with asplenia syndrome who underwent single ventricle palliation between 1990 and 2024. The primary end point was mortality, with risk factors assessed by Cox regression analysis over a mean follow‐up of 9.3?years.
Results: The median age at initial operation was 35?days, including 70 neonates (46%). Overall, 62 (41%) patients died, whereas 66 (44%) patients are alive post‐Fontan completion. Survival probabilities at 1 and 20?years were 75.7% (95% CI, 67.9?81.8) and 53.7% (95% CI, 44.5?62.0), respectively. TAPVC (P=0.014), PA (P=0.007), and greater than or equal to moderate atrioventricular valve regurgitation (P=0.040) emerged as independent risk factors for mortality in the overall cohort. In the TAPVC cohort, independent risk factors for mortality included PA (P=0.019), infracardiac TAPVC (P=0.045), and neonatal TAPVC repair (P=0.018). When stratified by the risk factors of TAPVC, PA, or greater than or equal to moderate atrioventricular valve regurgitation, survival probabilities did not differ between patients with none or 1 of these conditions (P=0.181) but were significantly lower in those with ?2 risk factors (P<0.001, at 15?years: 0, 72.9%; 1, 59.1%; ?2, 32.8%).
Conclusions: Survival after single ventricle palliation for asplenia syndrome remains suboptimal, particularly when TAPVC, PA, and greater than or equal to moderate atrioventricular valve regurgitation are present in combination rather than in isolation. Improved strategies or surgical techniques are required for this complex asplenia syndrome cohort. en-copyright= kn-copyright= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SanoShunji en-aut-sei=Sano en-aut-mei=Shunji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokudaYuhei en-aut-sei=Tokuda en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KimuraAyari en-aut-sei=Kimura en-aut-mei=Ayari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=StaffaSteven J. en-aut-sei=Staffa en-aut-mei=Steven J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZurakowskiDavid en-aut-sei=Zurakowski en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=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 Pediatric Cardiac Surgery Showa Medical University Toyosu 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=Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Boston Harvard Medical School kn-affil= affil-num=6 en-affil=Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Boston Harvard Medical School kn-affil= affil-num=7 en-affil=Department of Cardiovascular Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital 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=asplenia syndrome kn-keyword=asplenia syndrome en-keyword=atrioventricular valve regurgitation kn-keyword=atrioventricular valve regurgitation en-keyword=heterotaxy kn-keyword=heterotaxy en-keyword=pulmonary atresia kn-keyword=pulmonary atresia en-keyword=total anomalous pulmonary vein kn-keyword=total anomalous pulmonary vein END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=e70160 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 and Microbiological Characteristics of Invasive Group A Streptococcus Infection: Four Case Series of Re‐Emerging Pathogens en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Group A Streptococcus (GAS), particularly the M1UK lineage, has re-emerged as a major global public health concern following the COVID-19 pandemic, with a rise in invasive GAS (iGAS) and streptococcal toxic shock syndrome (STSS). Although STSS is under national surveillance in Japan, comprehensive molecular monitoring of iGAS infections remains limited, and the clinical characteristics of M1UK-associated iGAS have not been fully elucidated.
Methods: We retrospectively reviewed four consecutive iGAS cases requiring intensive care between March and May 2024. Detailed clinical, microbiological, and genomic investigations were performed to characterize the causative strains and their associated virulence profiles.
Results: All patients required respiratory and/or circulatory support with surgical debridement. Three cases involved necrotizing fasciitis, and one involved intra-abdominal infection secondary to ovarian tumor rupture. All four patients received penicillin G and clindamycin as definitive antimicrobial therapy, with two developing severe drug-related adverse events. Genotypic analysis identified three isolates as emm1 strains, including two M1UK lineage strains. The two M1UK isolates commonly harbored multiple superantigen genes. All isolates remained susceptible to β-lactam, clindamycin, and macrolide antibiotics.
Conclusion: This case series documents the identification of the M1UK lineage among critically ill patients with iGAS infections in Japan. Our findings support the need for continued molecular surveillance while reinforcing the importance of prompt surgical source control and appropriate antimicrobial therapy in the management of severe iGAS. en-copyright= kn-copyright= en-aut-name=OkaharaShuji en-aut-sei=Okahara en-aut-mei=Shuji 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=HamaguchiYuto en-aut-sei=Hamaguchi en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HishiikeMasanobu en-aut-sei=Hishiike en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MotoiYohei en-aut-sei=Motoi en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 ORCID= affil-num=1 en-affil=Department of Intensive Care, Okayama University Hospital 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 Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health 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=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=emm type kn-keyword=emm type en-keyword=Group A Streptococcus kn-keyword=Group A Streptococcus en-keyword=M1UK strain kn-keyword=M1UK strain en-keyword=necrotizing fasciitis kn-keyword=necrotizing fasciitis en-keyword=Streptococcus pyogenes kn-keyword=Streptococcus pyogenes END start-ver=1.4 cd-journal=joma no-vol=2006 cd-vols= no-issue=13 article-no= start-page=2075 end-page=2078 dt-received= dt-revised= dt-accepted= dt-pub-year=2006 dt-pub=200608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel Preparation of a 2′-O-Acetyl-1′-O-(4-methoxybenzyl)-l-biopterin Derivative, a Versatile Precursor for a Selective Synthesis of l-Biopterin Glycosides en-subtitle= kn-subtitle= en-abstract= kn-abstract=l-Rhamnose was converted, over a 13-step-sequence, into 2′-O-acetyl-N 2-(N,N-dimethylaminomethylene)-1′-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]-l-biopterin, an appropriately protected precursor of 1′-O- and 2′-O-monoglycosyl-l-biopterin. Thus, the first selective synthesis of these l-biopterin glycosides was accomplished by treatment of the precursor with either DDQ or sodium methoxide, then with tetra-O-benzoyl-α-d-glucopyranosyl bromide in the presence of silver triflate and tetramethylurea, followed by removal of the remaining protecting groups. 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=ToyotaHiroki en-aut-sei=Toyota en-aut-mei=Hiroki 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= en-keyword=L-biopterin glycosides kn-keyword=L-biopterin glycosides en-keyword=pteridine kn-keyword=pteridine en-keyword=limipterin kn-keyword=limipterin en-keyword=glycosylations kn-keyword=glycosylations en-keyword=protecting groups kn-keyword=protecting groups END start-ver=1.4 cd-journal=joma no-vol=999 cd-vols= no-issue=2 article-no= start-page=187 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=Constraining the Effects of Pre- and Post-accretionary Processes on Ryugu Insoluble Organic Matter en-subtitle= kn-subtitle= en-abstract= kn-abstract=Asteroidal and cometary fragments have been indicated as possible sources of the building blocks of life for the early Earth. Samples returned from the asteroid Ryugu are uncontaminated and contain organic matter. Such samples enable an investigation of the processes that formed and altered extraterrestrial organic matter. Here, the FTIR and Raman responses of insoluble organic matter (IOM) isolated from Ryugu particles and carbonaceous chondrites are reported. Several relationships were observed: (1) a strong positive correlation of CH2/CH3 plotted against aliphatics/C=C; (2) a strong negative correlation of CH2/CH3 plotted against δ15N and δ13C; and (3) strong negative correlations of FTIR band ratios plotted against Raman band parameters and D/G values. The data are not consistent with even moderate heating of the IOM, as indicated by CH2/CH3 ratios that are consistent with unheated carbonaceous chondrites. The C and N isotope data previously collected for each Ryugu particle preclude aqueous alteration based on our understanding of its effects on carbonaceous chondrite IOM. Mixing of several IOM endmembers was considered, but due to the similarities of the particle with the lowest CH2/CH3 ratio to the other particles in terms of its other spectroscopic parameters, this scenario was considered unlikely. Finally, the effects of irradiation were considered, and UV irradiation, in particular, was hypothesised to be the best explanation for the trends observed. Overall, the data highlight the importance of comprehensive data sets for revealing extraterrestrial processes, which could define the nature of organic matter reaching habitable environments, such as those of the Early Earth. en-copyright= kn-copyright= en-aut-name=PotiszilChristian en-aut-sei=Potiszil en-aut-mei=Christian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamanakaMasahiro en-aut-sei=Yamanaka en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtaTsutomu en-aut-sei=Ota en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakaguchiChie en-aut-sei=Sakaguchi en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitagawaHiroshi en-aut-sei=Kitagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaRyoji en-aut-sei=Tanaka en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KunihiroTak en-aut-sei=Kunihiro en-aut-mei=Tak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KobayashiKatsura en-aut-sei=Kobayashi en-aut-mei=Katsura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraEizo en-aut-sei=Nakamura en-aut-mei=Eizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=4 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=5 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=6 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=7 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=8 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=9 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=26394 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cold SiO2-rich slabs reaching the CMB revealed by the seifertite phase boundary en-subtitle= kn-subtitle= en-abstract= kn-abstract=A cold silica (SiO2)-rich subducted slab creates notable heterogeneity above the core-mantle boundary (CMB), influencing the evolution of the Earth’s mantle. This slab may exhibit characteristic anomalies in the longitudinal and shear wave seismic velocity above the CMB, attributed to the SiO2 phase transition into its dense polymorph, seifertite. However, the transition depth remains unclear due to the often-observed metastable phases in experiments. To address this long-standing challenge, we conducted laser-heated diamond anvil cell experiments with synchronised rapid X-ray diffraction measurements alongside theoretical calculations. The slope of the seifertite phase boundary was less steep than previously estimated, and consequently, the temperature profile of the slab crosses the boundary twice, like the post-perovskite transition. We observed a decrease in shear wave velocity beneath Hawaii and Central America, and we found anti-correlation in seismic wave velocities matching the depth range of the seifertite transition in a cold slab beneath Central America. This may provide evidence that a cold SiO2-rich slab descends towards the CMB. en-copyright= kn-copyright= en-aut-name=SinmyoRyosuke en-aut-sei=Sinmyo en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Kawaguchi-ImadaSaori en-aut-sei=Kawaguchi-Imada en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoRei en-aut-sei=Sato en-aut-mei=Rei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtsuruKeisuke en-aut-sei=Otsuru en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawaiKenji en-aut-sei=Kawai en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakumaHiroshi en-aut-sei=Sakuma en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SueharaShigeru en-aut-sei=Suehara en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=MaitaniShuhou en-aut-sei=Maitani en-aut-mei=Shuhou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Physics, School of Science and Technology, Meiji University kn-affil= affil-num=2 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=3 en-affil=Department of Earth and Planetary Science, School of Science, The University of Tokyo kn-affil= affil-num=4 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=5 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=6 en-affil=Environmental Circulation Composite Materials Group, National Institute for Materials Science kn-affil= affil-num=7 en-affil=Environmental Circulation Composite Materials Group, National Institute for Materials Science kn-affil= affil-num=8 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=9 en-affil=Department of Physics, School of Science and Technology, Meiji University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=8 article-no= start-page=1278 end-page=1287 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=First Total Synthesis and Structural Elucidation of Microcystbiopterin C, a Pterin Glycoside From a Microcystis Bloom en-subtitle= kn-subtitle= en-abstract= kn-abstract=The first total synthesis and unambiguous structural elucidation of microcystbiopterin C, a pterin glycoside isolated from a Microcystis bloom, has been achieved. Two candidate biopterin glycosides (5a and 5b) corresponding to the proposed structures of microcystbiopterin C were synthesized by glycosylation of a suitably protected biopterin derivative 10 with 2,4-di-O-benzoyl-6-deoxy-3-O-methyl-α-L-mannopyranosyl bromide (9) and the corresponding α-D-mannopyranosyl bromide (22), respectively, followed by stepwise deprotection. Detailed comparison of the NMR data and the specific rotation of compounds 5a and 5b with those of the natural product established that microcystbiopterin C possesses the structure of 2′-O-(6-deoxy-3-O-methyl-α-D-mannopyranosyl)biopterin (5b). 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=IwasakiKatsuya en-aut-sei=Iwasaki en-aut-mei=Katsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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= en-keyword=glycosylation kn-keyword=glycosylation en-keyword=microcystbiopterin C kn-keyword=microcystbiopterin C en-keyword=pteridine kn-keyword=pteridine en-keyword=pterin glycoside kn-keyword=pterin glycoside en-keyword=structural elucidation kn-keyword=structural elucidation END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=5 article-no= start-page=1093 end-page=1101 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260624 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Breast ultrasound screening in young adult women undergoing infertility treatment at an infertility clinic: a retrospective observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Young adult women are increasingly undergoing infertility treatment; however, evidence regarding breast cancer screening in this population remains limited. Given that most women in this age group have dense breast tissue, for which mammography has limited sensitivity, breast ultrasound (US) is often used as a screening modality. A diagnosis of breast cancer during infertility treatment may affect both oncologic management and reproductive planning. This study aimed to examine the clinical relevance of breast US in women in their 30s undergoing infertility treatment at an infertility clinic.
Methods We retrospectively analyzed 1,336 women aged 30?39 years who underwent screening breast US between November 1, 2018, and June 30, 2025. Analyses were performed on a per-woman basis, including only the first screening examination for each participant. Breast composition was categorized according to the BI-RADS 5th edition Atlas. Screening outcomes?including recall rate, positive predictive value (PPV), cancer detection rate, and US findings (mass and non-mass findings)?were assessed using medical records. The continuation of infertility treatment, defined as ongoing or resumed treatment during the diagnostic evaluation period, was descriptively evaluated as part of the clinical context.
Results Of the 1,336 women, 1,277 (95.6%) were classified as having dense breasts. A total of 140 (10.5%) women were recalled for further evaluation. In these recalled cases, 147 findings were identified, comprising 113 mass lesions (76.8%) and 34 non-mass findings (23.1%). Four breast cancers were identified, corresponding to a cancer detection rate of 0.30% and a PPV of 2.86%. Histological diagnoses included one mucinous carcinoma, two invasive carcinomas of no special type (NST), and one ductal carcinoma in situ (DCIS). Following diagnostic evaluation, 124 recalled women (88.6%) continued infertility treatment.
Conclusions Breast US screening in women in their 30s undergoing infertility treatment provides descriptive findings within a specific clinical setting. The observed cancer detection rate appears to be within the range reported in previous studies; however, direct comparisons are limited due to differences in study populations and clinical contexts. The clinical course following recall was described as part of the screening pathway. Further prospective and multicenter studies are required to clarify the clinical significance of breast US screening in this population. en-copyright= kn-copyright= en-aut-name=NakanoKanako en-aut-sei=Nakano en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiYuko en-aut-sei=Takahashi en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaedaReina en-aut-sei=Maeda en-aut-mei=Reina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SajiMarie en-aut-sei=Saji en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HirataRei en-aut-sei=Hirata en-aut-mei=Rei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YukawaMotomi en-aut-sei=Yukawa en-aut-mei=Motomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkudaShizuka en-aut-sei=Okuda en-aut-mei=Shizuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HiranoMiyu en-aut-sei=Hirano en-aut-mei=Miyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HabaraToshihiro en-aut-sei=Habara en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HayashiNobuyoshi en-aut-sei=Hayashi en-aut-mei=Nobuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Radiology, Okayama Couple’s Clinic Women’s Health Checkup Center kn-affil= affil-num=2 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil= kn-affil= affil-num=4 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Senior Embryologist, Okayama Couple’s Clinic kn-affil= affil-num=8 en-affil=Department of Radiology, Okayama Couple’s Clinic Women’s Health Checkup Center kn-affil= affil-num=9 en-affil=Department of Radiology, Okayama Couple’s Clinic Women’s Health Checkup Center kn-affil= affil-num=10 en-affil=Department of Medical Technology, Okayama Couple’s Clinic kn-affil= affil-num=11 en-affil=Department of Reproductive Medicine, Okayama Couple’s Clinic kn-affil= affil-num=12 en-affil=Department of Reproductive Medicine, Okayama Couple’s Clinic kn-affil= en-keyword=Breast ultrasonography kn-keyword=Breast ultrasonography en-keyword=Infertility treatment kn-keyword=Infertility treatment en-keyword=Women in their 30s kn-keyword=Women in their 30s en-keyword=Breast cancer screening kn-keyword=Breast cancer screening en-keyword=Multidisciplinary care kn-keyword=Multidisciplinary care END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=2 article-no= start-page=22 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=First-line fulvestrant vs. anastrozole in hormone receptor-positive advanced breast cancer: insights from the final FALCON trial results en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TakahashiYuko en-aut-sei=Takahashi en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamotoShogo en-aut-sei=Nakamoto en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= affil-num=1 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=Selective estrogen receptor degrader (SERD) kn-keyword=Selective estrogen receptor degrader (SERD) en-keyword=aromatase inhibitor (AI) kn-keyword=aromatase inhibitor (AI) en-keyword=endocrine therapy (ET) kn-keyword=endocrine therapy (ET) en-keyword=hormone receptor-positive (HR+) kn-keyword=hormone receptor-positive (HR+) en-keyword=advanced breast cancer kn-keyword=advanced breast cancer END start-ver=1.4 cd-journal=joma no-vol=713 cd-vols= no-issue= article-no= start-page=123411 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260705 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tungsten(VI) speciation in aqueous fluids at high pressures and high temperatures: in-situ Raman spectroscopy supported by DFT calculations en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tungsten (W) is mobile in magmatic?hydrothermal and deep subduction zone fluids, and its stable isotopes offer potential as tracers of fluid-rock interactions. We investigated W behavior in aqueous fluids using in-situ Raman spectroscopy on slightly acidic to alkaline Na2WO4 solutions (10?3?10?1 M W) and WO3?H2O/D2O ± NaCl systems up to 1.4 GPa and ?800 °C, with the band assignments supported by density functional theory (DFT) calculations. Raman spectra showed that the ν1 mode of WO42? persisted to the highest P?T conditions in alkaline fluids, while additional high-frequency bands near 950 or 973 cm?1 appeared at elevated T in the studied fluids. Their relative intensities depended on T, pH, and NaCl content; the 973 cm?1 band was only observed above 650 °C in Na-free fluids. Substitution of H2O with D2O did not significantly affect the band frequencies. Based on analogous molybdenum experiments, previous in-situ studies, and thermodynamic models, these high-T bands are assigned to mononuclear species rather than polynuclear species, consistent with the stepwise formation of hydrogentungstate anion, HWO4?, and then neutral tungstic acid, H2WO4, as T increases. DFT vibrational frequency calculations for HWO4?, H2WO4, and their D-substituted species support this interpretation, suggesting tetrahedral HWO4? and higher-coordinated H2WO4 as plausible species. The present study clarifies Raman band assignments for HWO4? and paratungstate A (W7O246?) to address previous ambiguities in the literature, and confirms that polynuclear species play a negligible role in high-T ore-forming fluids. The tetrahedral HWO4? appears to be a predominant transport species in NaCl-bearing metamorphic fluids and may govern stable W isotope fractionation during deep fluid-rock interactions. en-copyright= kn-copyright= en-aut-name=TakahashiNaoko en-aut-sei=Takahashi en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraMichihiko en-aut-sei=Nakamura en-aut-mei=Michihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamashitaShigeru en-aut-sei=Yamashita en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KagiHiroyuki en-aut-sei=Kagi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Earth Science, Graduate School of Science, Tohoku University kn-affil= affil-num=2 en-affil=Department of Earth Science, Graduate School of Science, Tohoku University kn-affil= affil-num=3 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=4 en-affil=Geochemical Research Center, Graduate School of Science, The University of Tokyo kn-affil= en-keyword=Tungsten kn-keyword=Tungsten en-keyword=Aqueous speciation kn-keyword=Aqueous speciation en-keyword=Hydrothermal fluids kn-keyword=Hydrothermal fluids en-keyword=Subduction zone kn-keyword=Subduction zone en-keyword=Diamond anvil cell kn-keyword=Diamond anvil cell en-keyword=Raman spectroscopy kn-keyword=Raman spectroscopy en-keyword=DFT calculations kn-keyword=DFT calculations END start-ver=1.4 cd-journal=joma no-vol=59 cd-vols= no-issue=1 article-no= start-page=104678 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2027 dt-pub=202701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of correcting beam hardening and detector response function in photon-counting X-ray imaging when using anti-coincidence mode en-subtitle= kn-subtitle= en-abstract= kn-abstract=X-ray imaging using photon-counting detectors (PCDs) allows for the calculation of quantitative images such as the effective atomic number (?eff). However, physical phenomena such as characteristic X-ray emission and charge sharing can cause incomplete total absorption events during signal generation, which reduces the accuracy of X-ray penetration analysis. To solve the problem, an anti-coincidence mode (ACM) has been developed, but complete correction has not been established. We aimed to investigate the accuracy of ?eff image when the proposed software-based corrections, namely beam hardening and response function corrections, are added to the hardware-based correction of the ACM. The response function was calculated using the Monte-Carlo simulation code. In a simulation study, we analyzed a phantom composed of virtual materials with ?eff values of 4?16. While sufficient accuracy cannot be achieved by applying only the ACM, it was demonstrated that low-noise ?eff images can be obtained by applying our correction. Furthermore, it was demonstrated that ?eff images of food samples can be generated by using actual non-destructive testing equipment with a 10?m/min transportation speed. In conclusion, our correction procedure can maximize the performance of PCDs, and our findings are essential for promoting imaging techniques concerning quantitative images. en-copyright= kn-copyright= en-aut-name=HayashiHiroaki en-aut-sei=Hayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishigamiRina en-aut-sei=Nishigami en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiDaiki en-aut-sei=Kobayashi en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KasueTakuya en-aut-sei=Kasue en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimotoNatsumi en-aut-sei=Kimoto en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsaharaTakashi en-aut-sei=Asahara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= affil-num=2 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=3 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=4 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=5 en-affil=Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= en-keyword=X-ray non-destructive testing kn-keyword=X-ray non-destructive testing en-keyword=Photon-counting detector kn-keyword=Photon-counting detector en-keyword=Coincidence summing kn-keyword=Coincidence summing en-keyword=CdTe detector kn-keyword=CdTe detector en-keyword=X-ray imaging kn-keyword=X-ray imaging END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=8291 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Water exchange process and bulk composition regulate slab dynamics and deep earthquakes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Water strongly influences deep mantle processes, including geochemical cycles, slab dynamics, and deep-focus earthquakes. Yet the stability and interactions of hydrous minerals with nominally anhydrous minerals (NAMs) under the water-undersaturated conditions of subducting slabs remain unclear. Here we show, using high-pressure and high-temperature experiments on MgO?SiO2?H2O systems (~2?wt% H2O), that hydrous minerals progressively dehydrate in the mantle transition zone, transferring water to NAMs such as wadsleyite and ringwoodite, while the cold slab core stays nearly dry. Rapid dehydration near the top of the lower mantle may generate fluids linked to the deepest earthquakes. Our results indicate that dry olivine transformations, rather than dehydration embrittlement, likely trigger most deep-focus earthquakes, and that hydration variations in NAMs influence slab deformation and stagnation above 660?km. The bulk Mg/Si ratio controls hydrous mineral stability, suggesting harzburgite transports water more efficiently than peridotite. en-copyright= kn-copyright= en-aut-name=ZhuJintao en-aut-sei=Zhu en-aut-mei=Jintao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TaoRenbiao en-aut-sei=Tao en-aut-mei=Renbiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZhangLifei en-aut-sei=Zhang en-aut-mei=Lifei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Center for High Pressure Science and Technology Advanced Research (HPSTAR) kn-affil= affil-num=3 en-affil=SKLab-DeepMinE, MOEKLab-OBCE, School of Earth and Space Sciences, Peking University kn-affil= affil-num=4 en-affil=Institute for Planetary Materials, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=44 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260622 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of a preoperative accuracy prediction model using machine learning for implant placement in static-guided surgery: retrospective observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose This study aimed to develop a machine learning model capable of preoperatively predicting three-dimensional implant placement errors at the implant apex in static-guided surgery and to identify the clinical features associated with placement accuracy.
Methods Clinical data partially derived from a previous observational study were analyzed. In total, 181 patients and 480 implants placed using fully static-guided surgery were included in this study. The outcome variable was defined as three-dimensional implant placement error at the implant apex relative to the preoperative simulation, dichotomized as less than 0.5 mm or ??0.5 mm. Twenty-one clinical and radiographic factors previously suggested to influence the placement accuracy were used as explanatory variables. The feature importance was evaluated using three gradient boosting decision tree models. Furthermore, a stacking model combining multiple classifiers was constructed, and the classification performance was assessed using ten-fold cross-validation.
Results The feature importance analysis identified 12 features associated with implant placement errors. The stacking model demonstrated superior classification performance compared to individual classifiers. The true positive rate was 0.73, false negative rate was 0.27, false positive rate was 0.14, and true negative rate was 0.86.
Conclusions The proposed stacking model correctly classified 86% of cases with implant placement error less than 0.5 mm and 73% of cases with implant placement error of ??0.5 mm. These findings suggest that the proposed model may support the preoperative evaluation of implant placement accuracy in static-guided surgeries. en-copyright= kn-copyright= en-aut-name=MinoTakuya en-aut-sei=Mino en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuokaYurina en-aut-sei=Matsuoka en-aut-mei=Yurina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorookaKen’ichi en-aut-sei=Morooka en-aut-mei=Ken’ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TokumotoKana en-aut-sei=Tokumoto en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimizuHiroaki en-aut-sei=Shimizu en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurosakiYoko en-aut-sei=Kurosaki en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Kimura-OnoAya en-aut-sei=Kimura-Ono en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KishimotoHiromitsu en-aut-sei=Kishimoto en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=MaekawaKenji en-aut-sei=Maekawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University kn-affil= affil-num=2 en-affil=Department of Semiconductor, Computer Science and Applied Mathematics, Graduate School of Science and Technology, Kumamoto University kn-affil= affil-num=3 en-affil=Division of Biomedical Engineering, Faculty of Advanced Science and Technology, Kumamoto University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, School of Medicine, Hyogo Medical University kn-affil= affil-num=5 en-affil=Shimizu Dental Clinic kn-affil= affil-num=6 en-affil=Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University kn-affil= affil-num=7 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, School of Medicine, Hyogo Medical University kn-affil= affil-num=9 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University kn-affil= en-keyword=Implant placement kn-keyword=Implant placement en-keyword=Accuracy kn-keyword=Accuracy en-keyword=Surgical guide kn-keyword=Surgical guide en-keyword=Machine learning kn-keyword=Machine learning en-keyword=Prediction algorithms kn-keyword=Prediction algorithms en-keyword=Decision trees kn-keyword=Decision trees en-keyword=Support vector machine kn-keyword=Support vector machine en-keyword=Sensitivity and specificity kn-keyword=Sensitivity and specificity END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=9 article-no= start-page=1890 end-page=1900 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260616 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Event-free survival and recurrence patterns after curative resection for locally advanced head and neck squamous cell carcinoma: single-institution real-world outcomes prior to the introduction of perioperative immunotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Perioperative immune checkpoint inhibitors have improved outcomes for resectable locally advanced head and neck squamous cell carcinoma (HNSCC). However, real-world surgical outcome data based on contemporary endpoints remain limited.
Methods We retrospectively analyzed 233 patients who underwent curative-intent surgery for locally advanced HNSCC. Event-free survival (EFS) and overall survival (OS) were evaluated. Unresectable recurrence-free survival (URFS) was explored as an additional endpoint to capture post-recurrence treatment feasibility. Prognostic factors were assessed using Cox proportional hazards models.
Results The median follow-up duration was 18.2 months. The 1-year EFS and OS rates were 67.1% and 89.4%, respectively. pN2 or higher disease, venous invasion, and perineural invasion were identified as independent adverse prognostic factors. Recurrence occurred in 34.8% of patients; among these, disease control at the last follow-up was achieved in 61.7% following curative-intent salvage treatment. Salvage surgery was associated with significantly improved post-recurrence survival (p? Conclusions This study provides real-world surgical outcome data for resectable locally advanced HNSCC prior to the introduction of perioperative immunotherapy. Recurrence remains a major clinical challenge, with heterogeneous post-recurrence outcomes influenced by treatment feasibility. These findings may help inform interpretation of treatment outcomes and clinical decision-making in the evolving era of perioperative immunotherapy. en-copyright= kn-copyright= en-aut-name=MakinoTakuma en-aut-sei=Makino en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaoiYuto en-aut-sei=Naoi en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasegawaGo en-aut-sei=Hasegawa en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamasakiTakuto en-aut-sei=Yamasaki en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NodaHiroki en-aut-sei=Noda en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimotoShohei en-aut-sei=Fujimoto en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoJunya en-aut-sei=Matsumoto en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Head and neck squamous cell carcinoma kn-keyword=Head and neck squamous cell carcinoma en-keyword=Surgery kn-keyword=Surgery en-keyword=Event-free survival kn-keyword=Event-free survival en-keyword=Recurrence kn-keyword=Recurrence en-keyword=Salvage surgery kn-keyword=Salvage surgery END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=3 article-no= start-page=26 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Antioxidant Activity of α-Tocopherol Metabolites in Comparison with the Parent Compound in Hepatocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=α-Tocopherol (αT) is the major form of vitamin E. Although it is metabolized in the liver when high levels of αT are present, the function of its metabolites has not yet been fully elucidated. This study aimed to evaluate the antioxidant activities of the αT metabolites, α-carboxyethyl hydroxychroman (αCEHC) and α-carboxymethylbutyl hydroxychroman (αCMBHC), in comparison with their parent compound. The pretreatment with αT and its metabolites showed a cytoprotective effect on the cytotoxicity induced by hydrogen peroxide in the mouse hepatoma Hepa1c1c7 cells. To elucidate the mechanism underlying the effect, in vitro assays and assessments of antioxidant-related genes and proteins were conducted. The in vitro assays showed that these compounds showed little scavenging activity against hydrogen peroxide but exhibited scavenging activity against DPPH radicals. On the other hand, assessments of antioxidant-related genes and proteins showed that αT and its metabolites significantly upregulated the expression of heme oxygenase-1 (HO-1) possibly through activation of the transcript factor Nrf2. Moreover, the cytoprotective effects of αT and its metabolites against hydrogen peroxide were counteracted by HO-1 inhibitors. These results suggest that not only αT but also its metabolites are potential cytoprotective factors against oxidative stress-induced cytotoxicity, and that their effects are exerted not through a direct action of scavenging hydrogen peroxide in the body, but rather through the regulation of gene expression. en-copyright= kn-copyright= en-aut-name=NishioTomoka en-aut-sei=Nishio en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AmakoKasumi en-aut-sei=Amako en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriyaDaiki en-aut-sei=Moriya en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=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=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= en-keyword=α-tocopherol kn-keyword=α-tocopherol en-keyword=α-carboxyethyl hydroxychroman kn-keyword=α-carboxyethyl hydroxychroman en-keyword=α-carboxymethylbutyl hydroxychroman kn-keyword=α-carboxymethylbutyl hydroxychroman en-keyword=metabolite kn-keyword=metabolite en-keyword=antioxidant activity kn-keyword=antioxidant activity END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=3 article-no= start-page=1178 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260123 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Chloride-Transporting OsHKT1;1 Splice Variants and Their Expression Profiles Under Salinity Stress in Rice en-subtitle= kn-subtitle= en-abstract= kn-abstract=OsHKT1;1, a member of the high-affinity K+ transporter (HKT) family, plays a key role in Na+ homeostasis and salinity tolerance in rice. In our previous study, multiple potential OsHKT1;1 splicing variants were identified, as well as the full-length (FL) OsHKT1;1 transcript from the salt-tolerant rice Pokkali. However, most previous studies focused solely on the full-length protein, leaving the transport functions of splice variants largely unexamined. In this study, we focused on the splice variant OsHKT1;1-V2 and compared its function and gene expression with those of OsHKT1;1-FL. Two-electrode voltage clamp experiments using Xenopus laevis oocytes revealed that the 1st start codon of OsHKT1;1-V2 is functional to exhibit bidirectional currents in bath solutions containing NaCl. Unlike the Na+-selective feature of OsHKT1;1-FL, OsHKT1;1-V2 primarily mediated Cl? transport with weak Na+ selectivity, which was supported by the higher Cl? accumulation in OsHKT1;1-V2?expressing oocytes. Subcellular localization analyses using oocytes and Arabidopsis mesophyll cells indicated plasma membrane localization of OsHKT1;1-V2, similar to OsHKT1;1-FL. Functional assays using a yeast mutant further indicated that OsHKT1;1-FL, but not OsHKT1;1-V2, mediates Na+ uptake. The same OsHKT1;1 variants were identified in the japonica cultivar Nipponbare, and OsHKT1;1-V2 of the cultivar showed Cl? transport properties similar to the one from Pokkali. Quantitative PCR analyses revealed higher abundance of OsHKT1;1-FL transcripts in Nipponbare than in Pokkali with markedly lower OsHKT1;1-V2 levels in Pokkali under salt stress. This study provides a new insight into HKT-mediated ion homeostasis under salinity stress. en-copyright= kn-copyright= en-aut-name=ImranShahin en-aut-sei=Imran en-aut-mei=Shahin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnoShuntaro en-aut-sei=Ono en-aut-mei=Shuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HorieRie en-aut-sei=Horie en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HorieTomoaki en-aut-sei=Horie en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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, Kurashiki 710-0046, Okayama, Japan kn-affil= affil-num=3 en-affil=Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University kn-affil= en-keyword=heterologous expression systems kn-keyword=heterologous expression systems en-keyword=Na+ selectivity kn-keyword=Na+ selectivity en-keyword=Cl? selectivity kn-keyword=Cl? selectivity en-keyword=rice kn-keyword=rice END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=3 article-no= start-page=e70101 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260826 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Critical role of cellular communication network factor 1 in early osteogenesis of mesenchymal stem cells primed by low‐intensity pulsed ultrasound and bone morphogenetic protein 2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=There is a known reciprocal inhibitory relationship between adipogenesis and osteogenesis in mesenchymal stem cells (MSCs). Our previous study showed that low-intensity pulsed ultrasound (LIPUS) did not promote osteogenesis of a murine MSC line C3H10T1/2, although LIPUS treatment suppressed adipogenesis. Therefore, we investigated the effect of a combination of an osteoinductive factor such as bone morphogenic protein-2 (BMP-2) and LIPUS treatment on osteogenesis. This combination significantly upregulated the gene expressions of BMP receptors and RUNX2, which is a key early osteogenic transcription factor. Interestingly, cellular communication network factor 1 (CCN1) was significantly increased at the mRNA and protein levels. Additionally, Runx2 expression was increased by a recombinant CCN1 protein and decreased in CRISPR-Cas9-generated Ccn1 knockout (KO) cells treated with the combination of LIPUS treatment and BMP-2. Moreover, Runx2 expression was recovered through the transfection of a Ccn1 expression plasmid into Ccn1 KO cells. These findings indicate that treatment with the combination of LIPUS treatment and BMP-2 promoted CCN1 production, and the CCN1 regulates the Runx2 expression in C3H10T1/2 cells, thus suggesting that CCN1 induced by mechanical stimulation and an osteoinductive factor plays a pivotal role in osteogenesis of MSCs. en-copyright= kn-copyright= en-aut-name=PaingHsu Myat en-aut-sei=Paing en-aut-mei=Hsu Myat kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakigawaMasaharu en-aut-sei=Takigawa en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=NishidaTakashi en-aut-sei=Nishida en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Faculty 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 Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=BMP‐2 kn-keyword=BMP‐2 en-keyword=CCN1 kn-keyword=CCN1 en-keyword=low‐intensity pulsed ultrasound (LIPUS) kn-keyword=low‐intensity pulsed ultrasound (LIPUS) en-keyword=mesenchymal stem cells kn-keyword=mesenchymal stem cells en-keyword=osteogenic differentiation kn-keyword=osteogenic differentiation END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=2 article-no= start-page=e70089 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Species‐specific roles of cellular communication network proteins in cartilage development: A comparative study using in vitro chondrogenic models en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cellular communication network (CCN) proteins are key matricellular regulators of cartilage development, yet their species-specific roles and network-level context remain unclear. This study integrated bulk RNA sequencing from chicken and mouse embryonic limb bud micromass cultures and human mesenchymal stem cell chondrogenesis with co-expression, protein?protein interaction, and ortholog analyses to construct CCN-centered regulatory networks across models. CCN1 and CCN2 emerged as dominant, conserved hubs enriched in collagen-containing extracellular matrix, cartilage development, and growth factor signaling modules, whereas CCN3?CCN6 showed lower context-dependent expression and connectivity. Functional and ortholog analyses revealed moderate pathway conservation, with high conservation of IGF, EGFR, and HIF-1 signaling, but reduced overlap in hypoxia and mechanosensing/Hippo categories, indicating species-specific tuning of environmental sensing. A focused ortholog screen identified multifunctional conserved hubs, including COL2A1, TGFBR1, SMAD3, RUNX2, HIF1A, IGF1, SPP1, and CD44. Single-cell RNA-seq meta-analysis of human iPSC-derived chondrogenesis and embryonic limb datasets showed CCN1/2 expression and homologous network activity peaking in mesenchymal and early chondrocyte populations, consistent with model-dependent persistence into hypertrophic and ossification stages in vivo. Overall, this work defines a conserved CCN1/2-centered axis integrating extracellular matrix formation with growth factor and mechanical cues, providing a framework for model selection and CCN-targeted cartilage regeneration strategies. en-copyright= kn-copyright= en-aut-name=WangZhangzheng en-aut-sei=Wang en-aut-mei=Zhangzheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=V?g?Judit en-aut-sei=V?g? en-aut-mei=Judit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Tak?csRoland en-aut-sei=Tak?cs en-aut-mei=Roland kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=P?liskaSzil?rd en-aut-sei=P?liska en-aut-mei=Szil?rd kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimEe Hyun en-aut-sei=Kim en-aut-mei=Ee Hyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JinEun‐Jung en-aut-sei=Jin en-aut-mei=Eun‐Jung kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KleerCelina G en-aut-sei=Kleer en-aut-mei=Celina G kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=PerbalBernard en-aut-sei=Perbal en-aut-mei=Bernard kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MattaCsaba en-aut-sei=Matta en-aut-mei=Csaba kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen kn-affil= affil-num=2 en-affil=Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen kn-affil= affil-num=3 en-affil=Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen kn-affil= affil-num=4 en-affil=Genomic Medicine and Bioinformatics Core Facility Department of Biochemistry and Molecular Biology Faculty of Medicine, University of Debrecen kn-affil= affil-num=5 en-affil=Department of Biomedical Materials Science Graduate School of JABA, Wonkwang University kn-affil= affil-num=6 en-affil=Department of Biomedical Materials Science Graduate School of JABA, Wonkwang University kn-affil= affil-num=7 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University, Faculty of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Department of Pathology, University of Michigan Medical School kn-affil= affil-num=9 en-affil=International CCN Society kn-affil= affil-num=10 en-affil=Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen kn-affil= en-keyword=cartilage regeneration kn-keyword=cartilage regeneration en-keyword=CCN kn-keyword=CCN en-keyword=chondrogenesis kn-keyword=chondrogenesis en-keyword=osteoarthritis kn-keyword=osteoarthritis en-keyword=regulatory network kn-keyword=regulatory network en-keyword=transcriptomics kn-keyword=transcriptomics END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=7 article-no= start-page=103553 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Patient-centred communication in radiographer education: A five-country comparative document analysis of curriculum and competency standards en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Patient-centred communication is fundamental to radiographic practice, particularly when patients experience anxiety or uncertainty during imaging or treatment. However, it remains unclear whether broad communication expectations in radiography education and professional standards are translated into explicit, observable behaviours and integrated into education and assessment. This comparative document analysis examined the representation of patient-centred communication in selected national-level documents from five countries, using listening-related behaviours as an illustrative example.
Methods: Selected national-level curriculum, accreditation, registration, capability, and competency documents from the United States, the United Kingdom, Australia, Canada, and Japan were analysed deductively using a predefined extraction framework. The framework assessed communication competence, listening-related behaviours, patient-centred care, patient/family relationships, interprofessional collaboration, education, and assessment.
Results: Communication was addressed in all five selected national-level document sets, although institutional framing differed. It was framed as a professional competency or capability in the United Kingdom and Australia, a role-based competency framework in Canada, clinical competency and accreditation requirements in the United States, and primarily as curriculum content in Japan. Explicit observable behavioural expectations, such as listening-related behaviours, were uncommon. Listening was explicitly defined only in the Australian capability standards; elsewhere, it was represented indirectly through broader concepts, such as patient interaction, information gathering, and interpersonal communication.
Conclusion: The selected documents differed in the explicitness, structure, and educational integration of communication-related standards, without implying differences in education quality or clinical outcomes. Defining patient-centred communication through observable behaviours may strengthen alignment among professional expectations, learning outcomes, feedback, and assessment.
Implications for practice: Operationalising patient-centred communication as observable behaviours may enhance curriculum mapping, feedback, and assessment in radiographer education. en-copyright= kn-copyright= en-aut-name=KomatsuY. en-aut-sei=Komatsu en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChikamotoY. en-aut-sei=Chikamoto en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsukanoK. en-aut-sei=Tsukano en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeS. en-aut-sei=Abe en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsudouS. en-aut-sei=Tsudou en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoY. en-aut-sei=Yamamoto en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanabeY. en-aut-sei=Tanabe en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Division of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Independent Researcher kn-affil= affil-num=3 en-affil=Department of Psychosomatic Medicine, Yokohama Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Radiological Technology, Faculty of Health Care Sciences, Jikei University of Health Care Sciences kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Faculty of Health Care Sciences, Jikei University of Health Care Sciences kn-affil= affil-num=6 en-affil=Division of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Division of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=Radiographer education kn-keyword=Radiographer education en-keyword=Patient-centred communication kn-keyword=Patient-centred communication en-keyword=Listening kn-keyword=Listening en-keyword=Competency standards kn-keyword=Competency standards en-keyword=Curriculum standards kn-keyword=Curriculum standards en-keyword=Document analysis kn-keyword=Document analysis END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=44 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=GWAS and Candidate Gene Prediction of Elemental Accumulation Traits in Rice Using a Multiparental Population en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rice plants accumulate essential elements to sustain physiological processes during growth and development and to ensure the nutritional quality of the grain as a food source. However, the genetic basis of elemental accumulation and the interrelationships among elemental concentrations across different tissues remain poorly understood. To conduct breeding aimed at improving the absorption characteristics of multiple interrelated elements, genetic analysis using experimental populations that retain diversity while sharing the genetic background of cultivated varieties is effective. Here we show genetic variations in the concentrations of 13 elements (P, K, Ca, Mg, As, Cd, Cr, Cu, Fe, Mo, Mn, Ni, and Zn) in rice straw at the flowering stage and grain at the mature stage using a multi-parent advanced generation inter-cross (MAGIC) population that derived from eight cultivars including both Japonica and Indica. Comprehensive evaluation of the correlation coefficients revealed divergences in the association between grain and straw for several combinations of elements. Haplotype-based genome-wide association studies (GWAS) identified 51 and 53 quantitative trait loci (QTLs) in straw and grain, respectively. In total, the 104 QTLs were grouped into 19 clusters and 60 independent QTLs. By leveraging the haplotype information from the MAGIC population, 52 candidate genes associated with the accumulation of Ca, Mg, Cd, Cu, Fe, and Mo were efficiently predicted from these QTLs, including both previously reported and novel genes. Among them, OsMOT1;1 encoding a molybdenum transporter, was predicted to be within a QTL associated with Mo accumulation in grain on chromosome 8. OsACA9, a homolog of autoinhibited Ca??-ATPases, was predicted within a QTL related to Ca accumulation in straw on chromosome 2. In addition, an unidentified gene, OsCML6, which is presumed to be involved in calcium signaling, was predicted to be a candidate for a Ca-accumulation QTL on chromosome 11. These findings offer insights into haplotypes and putative genes associated with element accumulation and trait interrelationships, providing valuable information for optimizing plant growth and enhancing grain nutritional quality in rice breeding programs. en-copyright= kn-copyright= en-aut-name=ZhangQian en-aut-sei=Zhang en-aut-mei=Qian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FurutaTomoyuki en-aut-sei=Furuta en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KashiharaKazunari en-aut-sei=Kashihara en-aut-mei=Kazunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OgawaDaisuke en-aut-sei=Ogawa en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YonemaruJunichi en-aut-sei=Yonemaru en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaJian Feng en-aut-sei=Ma en-aut-mei=Jian Feng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoToshio en-aut-sei=Yamamoto en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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 Crop Science, National Agriculture and Food Research Organization kn-affil= affil-num=5 en-affil=Research Center for Agricultural Information Technology, National Agriculture and Food Research Organization kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Rice kn-keyword=Rice en-keyword=Oryza sativa L. kn-keyword=Oryza sativa L. en-keyword=Multi-parent advanced generation inter-cross population kn-keyword=Multi-parent advanced generation inter-cross population en-keyword=Element accumulation kn-keyword=Element accumulation en-keyword=GWAS kn-keyword=GWAS en-keyword=QTL kn-keyword=QTL END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=6 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260130 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Report on the seventh Japanese meeting on biological function and evolution through interactions between hosts and transposable elements en-subtitle= kn-subtitle= en-abstract= kn-abstract=The seventh Japanese meeting on host?transposon interactions, titled “Biological Function and Evolution through Interactions between Hosts and Transposable Elements,” was held on September 1st and 2nd, 2025, at the National Institute of Genetics, as well as online. This meeting was supported by the National Institute of Genetics and aimed to bring together researchers studying the diverse roles of transposable elements (TEs) in genome function and evolution, as well as host defense systems against TE mobility, TE bursts during evolution, and intron mobility in mammals, insects, land plants, fungi, and protozoa. Here, we present the highlights of these discussions. en-copyright= kn-copyright= en-aut-name=IchiyanagiKenji en-aut-sei=Ichiyanagi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaYoko en-aut-sei=Ikeda en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SaitoKuniaki en-aut-sei=Saito en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Laboratory of Genome and Epigenome Dynamics, Department of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Invertebrate Genetics Laboratory, National Institute of Genetics kn-affil= en-keyword=Transposon kn-keyword=Transposon en-keyword=Retrotransposon kn-keyword=Retrotransposon en-keyword=Epigenetics kn-keyword=Epigenetics en-keyword=Transposition kn-keyword=Transposition en-keyword=Functionalization kn-keyword=Functionalization END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260831 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=裏表紙・英文目次 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260831 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=奥付 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1 article-no= start-page=293 end-page=293 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260831 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=本号執筆者紹介 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1 article-no= start-page=52 end-page=35 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260831 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Proof of Causaution in Asbestos Damage ? : Focused on The Construction Asbestos Benefit System （a Self-employed Person）. kn-title=アスベスト被害をめぐる因果関係の主張立証の壁? ―建設アスベスト給付金制度（１人親方等）の問題を中心に― en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TsujiH. en-aut-sei=Tsuji en-aut-mei=H. kn-aut-name=辻博明 kn-aut-sei=辻 kn-aut-mei=博明 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学名誉教授 END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1 article-no= start-page=292 end-page=54 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260831 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Implementation status of the Child Abuse Prevention Law of 1933 kn-title=昭和８年児童虐待防止法の実施状況 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OizumiY. en-aut-sei=Oizumi en-aut-mei=Y. kn-aut-name=大泉陽輔 kn-aut-sei=大泉 kn-aut-mei=陽輔 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学学術研究院社会文化科学学域 END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1 article-no= start-page=1 end-page=33 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260831 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Jan-Werner Mu?ller on cold war liberalism: moderate sensibility or “a fighting faith”? kn-title=ヤン＝ヴェルナー・ミュラーの冷戦リベラリズム論 ―節度ある感受性から戦闘的信念へ― en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OdagawaD. en-aut-sei=Odagawa en-aut-mei=D. kn-aut-name=小田川大典 kn-aut-sei=小田川 kn-aut-mei=大典 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学学術研究院社会文化科学学域 END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260831 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=表紙・目次 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= END start-ver=1.4 cd-journal=joma no-vol=192 cd-vols= no-issue= article-no= start-page=1 end-page=12 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Aspects of the Adoption of Simultaneous Teaching Methods in Japan in the Late 19th Century: A Perspective on the Transition from Early Modern to Modern Periods kn-title=19世紀後半日本における一斉教授法の受容の一断面 ― 近世・近代転換期の教育状況の視野 ― en-subtitle= kn-subtitle= en-abstract= kn-abstract=　近代日本における西洋教育の日本教育への影響を考察し，とくに世界で伝播のあったモニトリアル・システム（助教法）の日本教育における位置を検討する。19世紀後半は，近世の寺子屋の時代から近代の小学校の時代への転換期であった。国民教育の場としての小学校が整い，男女が就学する状況の形成があった。この過程において，日本がアメリカ経由で受容した一斉教授は，教師が教室で教授する方法であった。助教を用いる方法ではなかった。本稿は，近代日本ではモニトリアル･システムを基本的には経験しない展開と，一斉教授を行う教師の養成があったことを論じるものである。 en-copyright= kn-copyright= en-aut-name=KAJIIKazuaki en-aut-sei=KAJII en-aut-mei=Kazuaki kn-aut-name=梶井一暁 kn-aut-sei=梶井 kn-aut-mei=一暁 aut-affil-num=1 ORCID= affil-num=1 en-affil=Faculty of Education, Okayama University kn-affil=岡山大学学術研究院教育学域 en-keyword=近世・近代転換期 kn-keyword=近世・近代転換期 en-keyword=一斉教授 kn-keyword=一斉教授 en-keyword=個別教授 kn-keyword=個別教授 en-keyword=モニトリアル・システム kn-keyword=モニトリアル・システム en-keyword=教育伝播 kn-keyword=教育伝播 END start-ver=1.4 cd-journal=joma no-vol=192 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=表紙・目次 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue= article-no= start-page=100639 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=Interbacterial antagonism mediates plant growth modulation by rhizosphere synthetic communities in barley en-subtitle= kn-subtitle= en-abstract= kn-abstract=Microbial communities in plant roots are shaped by complex interbacterial interactions, yet how these interactions translate into plant fitness remains poorly understood. In this study, 127 bacterial isolates were obtained from barley (Hordeum vulgare L.) roots of two cultivars grown in a non-fertilized field, representing 45 genera and 72 species. Screening identified isolates with growth-promoting, growth-reducing, and neutral phenotypes. Co-inoculation experiments using synthetic communities (SynComs) demonstrated that growth-promoting isolates effectively cancelled the inhibitory effects of growth-reducing isolates on barley seedling growth. Mechanistic investigation revealed that growth-promoting isolates Variovorax sp. 14F-2.1 and Pseudomonas sp. 37A kill growth-reducing isolates Flavobacterium sp. 2D-1 through direct cell-to-cell contact. Deletion of the Type VI secretion system (T6SS) gene tssA in Variovorax sp. 14F-2.1 substantially reduced this activity, implicating T6SS as a key antagonistic mechanism. Phytohormone profiling revealed that growth-promoting and neutral isolates, but not growth-reducing isolates, produce cytokinins, and only Variovorax sp. 14F-2.1 could degrade IAA, suggesting a potential hormonal basis for differential growth effects. A two-year field microbiome study showed that fertilization regimen and seasonal sampling times were dominant drivers of rhizosphere community composition, while bacterial inoculation had limited and inconsistent effects on microbial diversity and plant growth under field conditions. These results demonstrate that interbacterial antagonism is a key determinant of community-level plant growth outcomes and highlight the complexity of translating laboratory inoculant effects to field settings. en-copyright= kn-copyright= en-aut-name=MahamudMd Asif en-aut-sei=Mahamud en-aut-mei=Md Asif kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PichaikarnRungnapa en-aut-sei=Pichaikarn en-aut-mei=Rungnapa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LatifMuhammad Ammar en-aut-sei=Latif en-aut-mei=Muhammad Ammar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuuraTakakazu en-aut-sei=Matsuura en-aut-mei=Takakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=SaishoDaisuke en-aut-sei=Saisho en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UngcharoenwiwatPakpimol en-aut-sei=Ungcharoenwiwat en-aut-mei=Pakpimol kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TaniAkio en-aut-sei=Tani en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=School of Science, Walailak 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 Science and Resources, Okayama University 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= affil-num=7 en-affil=School of Science, Walailak University kn-affil= affil-num=8 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Barley kn-keyword=Barley en-keyword=Rhizosphere microbiome kn-keyword=Rhizosphere microbiome en-keyword=SynCom kn-keyword=SynCom en-keyword=Bacterial antagonism kn-keyword=Bacterial antagonism en-keyword=Type VI secretion system kn-keyword=Type VI secretion system en-keyword=Phytohormone kn-keyword=Phytohormone END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=1 article-no= start-page=94 end-page=99 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251226 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Optimization of the External Directing Group Depending on the Substrates for the Regioselective C?H Alkenylation of Phenyl Ethers en-subtitle= kn-subtitle= en-abstract= kn-abstract=Using an external directing group (externalDG), we have succeeded in ortho-selective C?H alkenylation of various DG-free phenyl ethers, including bulky silyl ethers. Also, we demonstrated a strategy to develop regioselective C?H activation by optimizing externalDG depending on the substrate. The means for optimizing externalDG include the selection of the precursor, the addition of a Lewis acid, and changing the ratio of the precursor/Pd, to control the reactivity and regioselectivity. en-copyright= kn-copyright= en-aut-name=YanoKoki en-aut-sei=Yano en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SawadaDaisuke en-aut-sei=Sawada en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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= END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue=10 article-no= start-page=107906 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical characteristics and therapeutic dilemmas in nocardiosis: Insights from a case series en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Nocardiosis often requires prolonged antimicrobial therapy, and trimethoprim?sulfamethoxazole (TMP?SMX) is considered the cornerstone of treatment. However, TMP?SMX?related adverse events frequently complicate long-term therapy, and real-world data regarding treatment continuity and outcomes remain limited. Methods: We conducted a retrospective observational study of patients with Nocardia species isolated from clinical specimens at a tertiary-care academic hospital in Japan between January 2015 and April 2025. Clinical characteristics, antimicrobial therapy, adverse events, and outcomes were reviewed.
Results: Eleven cases were enrolled, with a median age of 65 years. The cohort comprised seven patients with severe nocardiosis (disseminated disease, brain abscess, and pneumonia in transplant recipients) and four patients with mild nocardiosis (cutaneous infection and pneumonia). Nine patients received TMP?SMX as part of the initial regimen, of whom seven required modification of therapy within 1 day to 3 months because of adverse events. Following modification of TMP?SMX, patients were treated with alternative regimens, including fluoroquinolone?and minocycline-based therapies, as well as β-lactam?containing combinations. Importantly, no cases of treatment failure or death were observed, and no relapses were identified during the available follow-up period, even among patients with those clinically complex diseases.
Conclusions: Although TMP?SMX is the first-line therapy for nocardiosis, the majority of our patients did not tolerate the drug. Nevertheless, favorable outcomes were observed with alternative regimens, even in patients with clinically complex disease, suggesting that alternative regimens may be reasonable options when TMP?SMX is not tolerated. 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=MiyaharaTomoyuki en-aut-sei=Miyahara en-aut-mei=Tomoyuki 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=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=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 General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=7 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Nocardiosis kn-keyword=Nocardiosis en-keyword=Treatment kn-keyword=Treatment en-keyword=Trimethoprim?sulfamethoxazole kn-keyword=Trimethoprim?sulfamethoxazole en-keyword=Alternative therapy kn-keyword=Alternative therapy en-keyword=Dose modification kn-keyword=Dose modification 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=20260509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fenestration Re-creation for Early Fontan Deterioration: Long-Term Hemodynamic and Clinical Outcomes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spontaneous closure of a Fontan fenestration may precipitate early hemodynamic deterioration in vulnerable patients. In such situations, fenestration re-creation may be considered as a rescue strategy when medical therapy is insufficient. However, the long-term hemodynamic consequences of this intervention remain poorly defined. We retrospectively reviewed 62 patients who underwent the Fontan procedure between January 2011 and December 2020 and subsequently experienced spontaneous fenestration closure. Patients were divided into two groups according to management strategy: those who underwent fenestration re-creation (Group 1, n?=?19) and those managed without re-creation (Group 2, n?=?43). Longitudinal hemodynamic data were analyzed using linear mixed models over a median follow-up of 10.2 years. Fenestration closed spontaneously at a median of 12 days (IQR 2.5?26.5) and initial re-creation was performed at the median of 42 days (IQR 11?213) postoperatively. Early and mide-term hemodynamic trends were broadly similar between groups, however, clear divergence emerged in the late follow-up. fenestration re-created patients demonstrated persistently higher central venous pressure and pulmonary vascular resistance, lower systemic vascular resistance, progressive increases in cardiac index, and declining oxygen saturation. Survival in this group remained above 80% during the mid-term follow-up but declined substantially in the late phase compared with patients without re-creation (52% vs. 85%, p?=?0.043). This was accompanied by higher incidences of protein-losing enteropathy/plastic bronchitis, thromboembolism, and severe cyanosis. Fenestration re-creation may provide temporary hemodynamic stabilization in early Fontan deterioration; however, its benefits appear to diminish in the late phase. These findings highlight the need for hemodynamically tailored management strategies and alternative therapeutic options for patients with deteriorating Fontan circulation. en-copyright= kn-copyright= en-aut-name=TranThi Hai Yen en-aut-sei=Tran en-aut-mei=Thi Hai Yen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuritaYoshihiko en-aut-sei=Kurita en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoMaiko en-aut-sei=Kondo en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukushimaYosuke en-aut-sei=Fukushima en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShigemitsuYusuke en-aut-sei=Shigemitsu en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawamotoYuya en-aut-sei=Kawamoto en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaraMayuko en-aut-sei=Hara en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwasakiTatsuo en-aut-sei=Iwasaki en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=BabaKenji en-aut-sei=Baba en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Pediatrics, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatric anesthesiology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Cardiovascular Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Fontan operation kn-keyword=Fontan operation en-keyword=Spontaneous fenestration closure kn-keyword=Spontaneous fenestration closure en-keyword=Fenestration recreation kn-keyword=Fenestration recreation en-keyword=Longitudinal hemodynamic changes kn-keyword=Longitudinal hemodynamic changes END start-ver=1.4 cd-journal=joma no-vol=1867 cd-vols= no-issue=4 article-no= start-page=149598 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202611 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cryo-EM structure of photosystem II D1-V185T mutant from Thermosynechococcus vestitus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosystem II (PSII) catalyzes water oxidation into electrons, protons and dioxygen at its catalytic center, a Mn4CaO5 cluster, utilizing light energy. An amino acid residue D1-V185 in the D1 protein is located close to the Mn4CaO5 cluster, and plays a critical role in its catalytic function. In this research we purified PSII dimers from a D1-V185T mutant of Thermosynechococcus vestitus and analyzed its structure using low-damage cryo-electron microscopy (cryo-EM) at a resolution of 1.88 ?. The results revealed the presence of multi-conformations at the mutation site. Unlike the wild-type valine, which does not allow water molecules to be able to form hydrogen-bonds with it, both conformations of the mutant formed hydrogen bonds with nearby water molecules, which leads to rearrangement of the hydrogen bond networks in the O1 and Cl-1 channels. In conformation-A, the mutated Thr residue forms a hydrogen bond with a water molecule W6, which creates a new channel that bypasses the original O1 channel. Due to the hydrophilic OH group of Thr, the side-chain of D1-Glu189 was attracted and shifted toward the mutant Thr residue. In conformation-B, it forms a hydrogen bond with a water molecule W9 in the Cl-1 channel, bringing W9 closer and thereby disrupting the hydrogen bond network of the Cl-1 channel. In addition, multi-conformations of D2-K317, which is a ligand of Cl-1, were found in the mutant. These changes alter the environment surrounding the Cl-1 ion and Mn4CaO5, thereby affecting the PSII water-oxidation activity. en-copyright= kn-copyright= en-aut-name=JiangHaowei en-aut-sei=Jiang en-aut-mei=Haowei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 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=5 ORCID= en-aut-name=SugiuraMiwa en-aut-sei=Sugiura en-aut-mei=Miwa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 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=2 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=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=Center for Transformative Science, School of Life Science and Technology and Shanghai Clinical Research and Trial Center, ShanghaiTech University kn-affil= affil-num=5 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=6 en-affil=Proteo-Science Research Center, Ehime University kn-affil= affil-num=7 en-affil=Research Institute for Interdisciplinary Science, Advanced Research Field and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Photosystem II kn-keyword=Photosystem II en-keyword=Oxygen-evolving complex kn-keyword=Oxygen-evolving complex en-keyword=Water-oxidation kn-keyword=Water-oxidation en-keyword=Structure kn-keyword=Structure en-keyword=Mutant kn-keyword=Mutant en-keyword=Cryo-EM kn-keyword=Cryo-EM en-keyword=Thermosynechococcus vestitus kn-keyword=Thermosynechococcus vestitus END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=4 article-no= start-page=399 end-page=409 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260403 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Graphene Oxide: Designing a Functional Smarter Material for Advanced Biomedicine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Graphene oxide (GO) has emerged as one of the most extensively studied two-dimensional (2D) materials, thanks to its large surface area and abundance of functional groups, which enable applications across energy, catalysis, electronics, construction, and mobility. Its exceptional dispersibility in water further expands its use in the biomedical field. However, researchers have consistently expressed concerns about the limited control over GO chemical composition and structural heterogeneity. These factors are often overlooked, strongly affecting the reproducibility in both synthesis and applications. Because GO is considered a promising platform for advanced drug delivery, achieving reproducible preparation and precise structural control is essential to make it a reliable alternative to the many nanomaterials currently being explored for nanomedicine.
Motivated by these challenges, we have focused our work on identifying and controlling the key parameters that govern GO structure and surface chemistry. Over the past decade, we have developed methods to produce GO with controlled and tunable chemical structures, clarified the reactivity of its major functional groups, and developed robust strategies for postfunctionalizing GO with therapeutic agents, targeting ligands, and imaging dyes. In parallel, we have established systematic approaches to evaluate GO biocompatibility and biodegradability, revealing how specific physicochemical features influence biological responses and clearance pathways.
Together, these findings provide a unified framework linking GO synthesis, chemical modification, and biological behavior. By integrating chemical control, functional performance, and safety assessment, our work outlines a coherent strategy for the rational design of GO-based biomedical materials. We believe that this Account offers a solid foundation for the targeted exploitation of GO in nanomedicine and will help facilitate its eventual clinical translation. en-copyright= kn-copyright= en-aut-name=M?nard-MoyonC?cilia en-aut-sei=M?nard-Moyon en-aut-mei=C?cilia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=BiancoAlberto en-aut-sei=Bianco en-aut-mei=Alberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS 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= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=22258 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260711 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Microstructural changes in irradiated teeth revealed by swept-source optical coherence tomography en-subtitle= kn-subtitle= en-abstract= kn-abstract=Radiation-induced caries is a late complication of radiotherapy for head and neck cancers. Although direct irradiation-induced changes in tooth structure may contribute to its development, these changes have not been fully characterized. This study evaluated irradiation-associated microstructural alterations and tissue density changes in human teeth using swept-source optical coherence tomography (SS-OCT). Eight extracted fully impacted human third molars were assigned to irradiated and non-irradiated groups (n?=?4 each). The irradiated group received X-rays at a total dose of 70 Gy, a clinically relevant dose in definitive radiotherapy for head and neck cancer. A total of 64 SS-OCT cross-sectional images were obtained and analyzed, with 32 images from each group, including 16 from the coronal area on the occlusal side and 16 from the cervical area. Microcrack-like features were observed in 100% (16/16) of irradiated and 31.3% (5/16) of non-irradiated images in the coronal area on the occlusal side, and in 43.8% (7/16) and 0% (0/16) of images in the cervical area, respectively. Attenuation coefficients were significantly higher in irradiated enamel and dentin. These findings suggest that irradiation-induced microstructural changes in extracted human teeth in vitro may contribute to increased susceptibility to radiation-induced caries. en-copyright= kn-copyright= en-aut-name=MatsuzakiKumiko en-aut-sei=Matsuzaki en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuzakiHidenobu en-aut-sei=Matsuzaki en-aut-mei=Hidenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TabataTomoko en-aut-sei=Tabata en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AoyamaHideki en-aut-sei=Aoyama en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshioKotaro en-aut-sei=Yoshio en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KosakiHirotaka en-aut-sei=Kosaki en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OharaNaoko en-aut-sei=Ohara en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SadrAlireza en-aut-sei=Sadr en-aut-mei=Alireza kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SogaYoshihiko en-aut-sei=Soga en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShimadaYasushi en-aut-sei=Shimada en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Oral Diagnosis and Dentomaxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= affil-num=4 en-affil=Central Division of Radiology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Biomimetics Biomaterials Biophotonics Biomechanics & Technology Laboratory, Department of Restorative Dentistry, Magnuson Health Sciences Center, University of Washington kn-affil= affil-num=9 en-affil=Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= en-keyword=Radiation-induced caries kn-keyword=Radiation-induced caries en-keyword=Dental enamel kn-keyword=Dental enamel en-keyword=Dentin kn-keyword=Dentin en-keyword=Radiation effects kn-keyword=Radiation effects en-keyword=Swept-source optical coherence tomography kn-keyword=Swept-source optical coherence tomography END start-ver=1.4 cd-journal=joma no-vol=138 cd-vols= no-issue=2 article-no= start-page=58 end-page=61 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260803 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A case of autoamputated primary uterine diffuse large B-cell lymphoma treated with Pola-R-CHP therapy and CNS recurrence prophylaxis kn-title=自然脱落した子宮原発 DLBCL に対して Pola-R-CHP 療法と CNS 再発予防を行った１例 en-subtitle= kn-subtitle= en-abstract= kn-abstract=　A 55-year-old woman presented to her local physician with the chief complaint of genital bleeding. A 22×19-mm mass was noted on the patient's cervix, and during the internal examination the mass auto-amputated. The pathological examination of the auto-amputated mass revealed diffuse large B-cell lymphoma (DLBCL). An examination by F-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) showed FDG uptake at physiological levels in the cervix, with no abnormal uptake in other organs. Cervical tissue was sampled after the spontaneous detachment of the cervical mass, and the biopsy of the cervical mass did not reveal findings suggestive of lymphoma. Six courses of chemotherapy with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisolone (Pola-R-CHP) plus an intramedually injection of methotrexate, cytarabine, and predonisolone (IT-triple), followed by two courses of high-dose intrathecal methotrexate (HD-MTX) were adiministered, and the patient has remained recurrence-free for the more than 8 months since the completion of this treatment. Primary uterine DLBCL is an extremely rare disease with a high rate of recurrence in the central nervous system and a poor prognosis. Our search of the relevant literature identified very few reports describing the prognoses of cases with spontaneous tumor detachment. en-copyright= kn-copyright= en-aut-name=OsadaHikaru en-aut-sei=Osada en-aut-mei=Hikaru kn-aut-name=長田晃 kn-aut-sei=長田 kn-aut-mei=晃 aut-affil-num=1 ORCID= en-aut-name=KimuraMaiko en-aut-sei=Kimura en-aut-mei=Maiko kn-aut-name=木村真衣子 kn-aut-sei=木村 kn-aut-mei=真衣子 aut-affil-num=2 ORCID= en-aut-name=MuneishiManaka en-aut-sei=Muneishi en-aut-mei=Manaka kn-aut-name=宗石愛花 kn-aut-sei=宗石 kn-aut-mei=愛花 aut-affil-num=3 ORCID= en-aut-name=MurayamaKozo en-aut-sei=Murayama en-aut-mei=Kozo kn-aut-name=村山晃三 kn-aut-sei=村山 kn-aut-mei=晃三 aut-affil-num=4 ORCID= en-aut-name=NiiyaDaigo en-aut-sei=Niiya en-aut-mei=Daigo kn-aut-name=新谷大悟 kn-aut-sei=新谷 kn-aut-mei=大悟 aut-affil-num=5 ORCID= en-aut-name=TakeuchiMakoto en-aut-sei=Takeuchi en-aut-mei=Makoto kn-aut-name=竹内誠 kn-aut-sei=竹内 kn-aut-mei=誠 aut-affil-num=6 ORCID= en-aut-name=FujiiSoichiro en-aut-sei=Fujii en-aut-mei=Soichiro kn-aut-name=藤井総一郎 kn-aut-sei=藤井 kn-aut-mei=総一郎 aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Hematology, Japanese Red Cross Okayama Hospital kn-affil=岡山赤十字病院　血液内科 affil-num=2 en-affil=Department of Hematology, Japanese Red Cross Okayama Hospital kn-affil=岡山赤十字病院　血液内科 affil-num=3 en-affil=Department of Hematology, Japanese Red Cross Okayama Hospital kn-affil=岡山赤十字病院　血液内科 affil-num=4 en-affil=Department of Hematology, Japanese Red Cross Okayama Hospital kn-affil=岡山赤十字病院　血液内科 affil-num=5 en-affil=Department of Hematology, Japanese Red Cross Okayama Hospital kn-affil=岡山赤十字病院　血液内科 affil-num=6 en-affil=Department of Hematology, Japanese Red Cross Okayama Hospital kn-affil=岡山赤十字病院　血液内科 affil-num=7 en-affil=Department of Hematology, Japanese Red Cross Okayama Hospital kn-affil=岡山赤十字病院　血液内科 en-keyword=びまん性大細胞型Ｂ細胞リンパ腫 (diffuse large B-cell lymphoma) kn-keyword=びまん性大細胞型Ｂ細胞リンパ腫 (diffuse large B-cell lymphoma) en-keyword=子宮原発リンパ腫 (primary uterine lymphoma) kn-keyword=子宮原発リンパ腫 (primary uterine lymphoma) en-keyword=Pola-R-CHP療法 (Pola-R-CHP regimen) kn-keyword=Pola-R-CHP療法 (Pola-R-CHP regimen) en-keyword=HD-MTX療法 (HD-MTX regimen) kn-keyword=HD-MTX療法 (HD-MTX regimen) END start-ver=1.4 cd-journal=joma no-vol=138 cd-vols= no-issue=2 article-no= start-page=31 end-page=34 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260803 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2025 Incentive Award of the Okayama Medical Association in General Medical Science (2025 Yuuki Prize) kn-title=令和７年度岡山医学会賞　総合研究奨励賞（結城賞） en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KambaraYui en-aut-sei=Kambara en-aut-mei=Yui kn-aut-name=神原由依 kn-aut-sei=神原 kn-aut-mei=由依 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=岡山大学大学院医歯薬学総合研究科　血液・腫瘍・呼吸器内科学 END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue= article-no= start-page=1842408 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260820 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=New mechanistic insight into SARM1 activation: TRIM32-mediated ubiquitination is a key lever that actuates SARM1’s catalytic action, leading to axon degeneration and cell death en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sterile alpha and TIR motif-containing protein 1 (SARM1) is an enzyme that cleaves nicotinamide adenine dinucleotide (NAD+) and plays a role in disrupting neural circuits through axon degeneration and cell death. SARM1 is activated by changes in the nicotinamide mononucleotide (NMN)/NAD+ ratio and by various post-translational modifications, but its complete regulatory mechanism remains poorly understood. Here, we report that tripartite motif-containing protein 32 (TRIM32) activates SARM1 through specific ubiquitination triggered by anticancer drug treatment. TRIM32 promotes the attachment of Lys27-linked ubiquitin chains to Lys173 and Lys375 within the ARM domain, which is an autoinhibitory region of SARM1. This ubiquitination by TRIM32 increases SARM1’s NAD+-cleaving catalytic activity and enhances its ability to induce neurite degeneration and cell death. A mutant form of TRIM32 lacking the enzymatically active RING domain fails to promote SARM1 ubiquitination, and reducing TRIM32 levels decreases SARM1 ubiquitination. Additionally, ubiquitin-specific peptidase 13 (USP13), a known negative regulator of SARM1, can deubiquitinate SARM1. These findings suggest that TRIM32 is a key regulator of axon degeneration and cell death through its ubiquitination of SARM1. en-copyright= kn-copyright= en-aut-name=MurataHitoshi en-aut-sei=Murata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoKen-ichi en-aut-sei=Yamamoto en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=axon degeneration kn-keyword=axon degeneration en-keyword=NAD?+ kn-keyword=NAD?+ en-keyword=SARM1 kn-keyword=SARM1 en-keyword=TRIM32 kn-keyword=TRIM32 en-keyword=ubiquitination kn-keyword=ubiquitination END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=19 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260403 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Potential effects of intradialytic exercise therapy on physical performance in hemodialysis patients based on the intervention period: a systematic review and meta-analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Intradialytic exercise during hemodialysis (HD) improves physical function and shows high adherence. In Japan, the 2018 guideline by the Japanese Society of Renal Rehabilitation supports intradialytic exercise, but medical insurance only covers the first 90 days. As new studies have emerged since the guideline was published, we conducted a systematic review and meta-analysis to evaluate the impact and optimal duration of exercise interventions beyond 12 weeks.
Methods We followed a preregistered protocol (PROSPERO CRD42025642273) and PRISMA-P guidelines. Randomized controlled trials of adult patients undergoing HD performing structured exercise were identified via MEDLINE database (PubMed, March 2017?November 2024) and ICHUSHI-Web database. Two independent reviewers screened studies, extracted data, and assessed risk of bias using Cochrane RoB 2.0. Outcomes included peak oxygen uptake (VO2peak), maximal oxygen uptake (VO2max), 6 min walk distance, timed up and go (TUG) test, handgrip strength, sit-to-stand (STS) performance, and biochemical measures (hemoglobin, standard weekly urea Kt/V [std Kt/V]). Pooled mean differences (MD) with 95% confidence intervals (CI) were calculated using a mixed-effects model (Hartung?Knapp?Sidik?Jonkman method).
Results A total of 71 studies, including 43 newly identified studies, were included. Risk of bias was moderate-to-high. Interventions?>?12 weeks significantly improved 6 min walking distance (MD 52.4 m [95% CI 35.4?69.3], p??12 weeks of exercise.
Conclusions Our findings suggest that exercise interventions lasting more than 12 weeks can enhance physical performance. Nevertheless, the applicability of these results to older patients remains uncertain, as most evidence is derived from middle-aged cohorts.
Trial registration Registered in the PROSPERO database (CRD42025642273). en-copyright= kn-copyright= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HondaYu en-aut-sei=Honda en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KojimaShigeki en-aut-sei=Kojima en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakeHiromasa en-aut-sei=Miyake en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimotoMasatoshi en-aut-sei=Nishimoto en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HishikawaAkihito en-aut-sei=Hishikawa en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TonomuraShun en-aut-sei=Tonomura en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SofueTadashi en-aut-sei=Sofue en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiNaohiko en-aut-sei=Fujii en-aut-mei=Naohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SaitohMasakazu en-aut-sei=Saitoh en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NaritaIchiei en-aut-sei=Narita en-aut-mei=Ichiei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamagataKunihiro en-aut-sei=Yamagata en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HoshinoJunichi en-aut-sei=Hoshino en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawarazakiHiroo en-aut-sei=Kawarazaki en-aut-mei=Hiroo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SakuradaTsutomu en-aut-sei=Sakurada en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Internal Medicine, Teikyo University Hospital Mizonokuchi kn-affil= affil-num=2 en-affil=Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine kn-affil= affil-num=3 en-affil=Kojima Kidney and Dialysis Clinic kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Nara Medical University kn-affil= affil-num=6 en-affil=Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine kn-affil= affil-num=8 en-affil=Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Department of Nephrology, Hyogo Prefectural Nishinomiya Hospital kn-affil= affil-num=10 en-affil=Department of Physical Therapy, Faculty of Health Science, Juntendo University kn-affil= affil-num=11 en-affil=Niigata Institute for Health and Sports Medicine, Niigata Sports Association kn-affil= affil-num=12 en-affil=Department of Nephrology, Institute of Medicine, University of Tsukuba kn-affil= affil-num=13 en-affil=Division of Preventive and Sports Nephrology, Graduate School of Comprehensive Human Sciences, Tokyo Women’s Medical University kn-affil= affil-num=14 en-affil=Department of Internal Medicine, Teikyo University Hospital Mizonokuchi kn-affil= affil-num=15 en-affil=Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine kn-affil= en-keyword=Intradialytic exercise kn-keyword=Intradialytic exercise en-keyword=Physical performance kn-keyword=Physical performance en-keyword=Exercise period kn-keyword=Exercise period en-keyword=Short physical performance battery kn-keyword=Short physical performance battery en-keyword=Handgrip strength kn-keyword=Handgrip strength en-keyword=Systematic review kn-keyword=Systematic review en-keyword=Meta-analysis kn-keyword=Meta-analysis END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=13 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260308 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Duration-stratified effects of exercise therapy on health-related quality of life in hemodialysis patients: a systematic review and meta-analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Patients on maintenance hemodialysis (HD) have reduced health-related quality of life (HRQoL). Structured exercise therapy is recommended, but domain-specific effects and the influence of intervention duration remain uncertain. This study evaluated the impact of structured exercise therapy on multiple HRQoL domains, including fatigue and depression, stratified by intervention duration.
Methods: We conducted a systematic review and meta-analysis, searching MEDLINE (PubMed) through November 2024. The protocol was registered in PROSPERO (CRD42025642273). We included trials comparing structured exercise with non-exercise controls in adult HD patients. Primary outcomes were Short Form (SF)-36 Physical and Mental Component Summaries (PCS, MCS), fatigue, pain, general health, and depression (Beck Depression Inventory). Data were synthesized using random-effects models, stratified by intervention duration (??3 versus?>?3 months). Risk of bias was assessed using the Cochrane RoB 2 tool.
Results: We identified 94 randomized controlled trials (5228 participants); 22 reported HRQoL outcomes and were meta-analyzed. Exercise significantly improved fatigue (mean difference [MD]?+?7.27, 95% confidence interval [CI] 4.75?9.80) and reduced depressive symptoms in?>?3-month trials (MD??7.62, 95% CI??8.34 to??6.90); no???3-month depression data were available. In overall analyses, general health (MD?+?11.59, 95% CI 6.98?16.21) and PCS (MD?+?5.83, 95% CI 0.71?10.94) improved, whereas MCS (MD?+?7.60, 95% CI??3.75 to 18.94) and pain (MD?+?2.19, 95% CI??4.41 to 8.79) showed no clear benefit. Short-term interventions (??3 months) yielded significant improvements in pain and general health. In longer-term interventions (>?3 months), general health estimates were similar in magnitude but statistically nonsignificant, and pain effects were also nonsignificant with substantial heterogeneity. Fatigue improved in both duration strata.
Conclusions: Structured exercise therapy appears to improve fatigue in patients on maintenance HD and may provide additional gains in PCS and general health with interventions longer than 3 months. Improvements in depressive symptoms were observed from limited evidence, and duration-specific effects remain uncertain because no trials assessed depression at???3 months. Effects on pain and MCS remain uncertain owing to substantial heterogeneity. Larger long-term trials are needed to clarify the sustainability of HRQoL benefits beyond 3 months. en-copyright= kn-copyright= en-aut-name=HondaYu en-aut-sei=Honda en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KojimaShigeki en-aut-sei=Kojima en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakeHiromasa en-aut-sei=Miyake en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimotoMasatoshi en-aut-sei=Nishimoto en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HishikawaAkihito en-aut-sei=Hishikawa en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TonomuraShun en-aut-sei=Tonomura en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SofueTadashi en-aut-sei=Sofue en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiNaohiko en-aut-sei=Fujii en-aut-mei=Naohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SaitohMasakazu en-aut-sei=Saitoh en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NaritaIchiei en-aut-sei=Narita en-aut-mei=Ichiei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamagataKunihiro en-aut-sei=Yamagata en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HoshinoJunichi en-aut-sei=Hoshino en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawarazakiHiroo en-aut-sei=Kawarazaki en-aut-mei=Hiroo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SakuradaTsutomu en-aut-sei=Sakurada en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Teikyo University Hospital Mizonokuchi kn-affil= affil-num=3 en-affil=Kojima Kidney and Dialysis Clinic kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Nara Medical University kn-affil= affil-num=6 en-affil=Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine kn-affil= affil-num=8 en-affil=Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Department of Nephrology, Hyogo Prefectural Nishinomiya Hospital kn-affil= affil-num=10 en-affil=Department of Physical Therapy, Faculty of Health Science, Juntendo University kn-affil= affil-num=11 en-affil=Niigata Institute for Health and Sports Medicine, Niigata Sports Association kn-affil= affil-num=12 en-affil=Department of Nephrology, Institute of Medicine, University of Tsukuba kn-affil= affil-num=13 en-affil=Department of Nephrology, Tokyo Women’s Medical University kn-affil= affil-num=14 en-affil=Department of Internal Medicine, Teikyo University Hospital Mizonokuchi kn-affil= affil-num=15 en-affil=Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine kn-affil= en-keyword=Hemodialysis kn-keyword=Hemodialysis en-keyword=Exercise therapy kn-keyword=Exercise therapy en-keyword=Intradialytic exercise kn-keyword=Intradialytic exercise en-keyword=Health-related quality of life kn-keyword=Health-related quality of life en-keyword=Fatigue kn-keyword=Fatigue en-keyword=Depression kn-keyword=Depression en-keyword=Randomized controlled trials kn-keyword=Randomized controlled trials en-keyword=Meta-analysis kn-keyword=Meta-analysis END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=2 article-no= start-page=527 end-page=535 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260516 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Microcontroller-Integrated Multichannel Time Detector for Paper-Based Analytical Devices ? Applications to Viscosity Measurements in Saliva Analysis and Protease-Activity Assays en-subtitle= kn-subtitle= en-abstract= kn-abstract=We designed and developed a microcontroller-integrated multichannel time detection system that uses a microfluidic paper-based analytical device (?PAD) to measure liquid viscosity. This detection system is equipped with ten detectors to enhance the throughput of the measurements. The ?PAD utilizes capillary action to determine viscosity based on the flow time of a liquid sample. A conductivity detection system begins counting the flow time when a sample is introduced and stops the count when the sample reaches the detection electrode. Sodium chloride (NaCl) was pre-deposited in the detection channel of the ?PAD to enhance the conductivity of non-conductive samples, and Grade 1 CHR chromatography paper was selected as the optimal vehicle for substrates after comparing various channel widths, paper types, and channel lengths. The device demonstrated a linear correlation between flow time and viscosity for bovine serum albumin (BSA) and glucose solutions, which validates the theoretical model. The time readout measured protease activity when gelatin was used as a substrate and revealed an activity order of bromelain?>?papain?>?trypsin. The practical applicability of this system was further confirmed by testing real saliva samples, which demonstrated that the viscosity of saliva decreases rapidly after collection. Moreover, the results indicate that saliva viscosity was increased during extended durations of exercise. Overall, this ?PAD system provides a simple, low-cost, and portable solution for viscosity measurement, with potential applications in clinical diagnostics and field measurements. en-copyright= kn-copyright= en-aut-name=RenJianchao en-aut-sei=Ren en-aut-mei=Jianchao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DanchanaKaewta en-aut-sei=Danchana en-aut-mei=Kaewta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanetaTakashi en-aut-sei=Kaneta en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Chemistry, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry, Okayama University kn-affil= en-keyword=Paper-based analytical device kn-keyword=Paper-based analytical device en-keyword=Time detector kn-keyword=Time detector en-keyword=Multichannel kn-keyword=Multichannel en-keyword=Viscosity kn-keyword=Viscosity en-keyword=Enzyme assay kn-keyword=Enzyme assay en-keyword=Saliva kn-keyword=Saliva END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=5 article-no= start-page=e70145 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260821 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Transforming Life Science Through Chromosome‐Level Genome Assemblies en-subtitle= kn-subtitle= en-abstract= kn-abstract=Advances in long-read sequencing and Hi?C scaffolding have made chromosome-level genome assembly increasingly accessible to individual laboratories, shifting genome research from large consortium-led projects toward investigator-driven studies across diverse taxa. This transition allows researchers to select organisms based on biological questions rather than the prior availability of genomic resources. In this review, we summarize the core experimental and computational steps for generating, evaluating, and annotating chromosome-level assemblies, and examine how they have advanced research in non-model organisms and genetically complex systems. Representative case studies illustrate four major contributions: resolving structural variation and lineage-specific genome architecture, linking genome organization to phenotypic innovation and plasticity, reconstructing deep chromosome evolution and macrosynteny, and distinguishing homologous and homoeologous chromosomes in polyploid genomes. These examples show that chromosome-level assemblies provide more than complete reference sequences. They establish a continuous genomic coordinate system through which genes, regulatory elements, transposable element insertions, sequence variants, and cellular states can be interpreted within broader chromosomal, population, and evolutionary contexts. We describe this integrative perspective as “glocal biology.” Future progress will require pangenomic, population-scale, and haplotype-resolved resources integrated with multi-omics and functional analyses. Collectively, chromosome-level genomics is reshaping life science by embedding molecular functions within chromosomal and evolutionary contexts. en-copyright= kn-copyright= en-aut-name=KonTetsuo en-aut-sei=Kon en-aut-mei=Tetsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KataokaKosuke en-aut-sei=Kataoka en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LuoYi‐Jyun en-aut-sei=Luo en-aut-mei=Yi‐Jyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WibisanaJohannes Nicolaus en-aut-sei=Wibisana en-aut-mei=Johannes Nicolaus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TogaKouhei en-aut-sei=Toga en-aut-mei=Kouhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UnoNarumi en-aut-sei=Uno en-aut-mei=Narumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MondenYuki en-aut-sei=Monden en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HamadaMayuko en-aut-sei=Hamada en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Neurosciences and Developmental Biology, University of Vienna kn-affil= affil-num=2 en-affil=Graduate School of Engineering, Tokyo University of Agriculture and Technology kn-affil= affil-num=3 en-affil=Biodiversity Research Center, Academia Sinica kn-affil= affil-num=4 en-affil=Genomics and Regulatory Systems Unit, Okinawa Institute of Science and Technology Graduate University kn-affil= affil-num=5 en-affil=Laboratory of BioDX, PtBio Co‐Creation Research Center, Genome Editing Innovation Center, Hiroshima University kn-affil= affil-num=6 en-affil=Laboratory of Bioengineering, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences 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=Ushimado Marine Institute, Okayama University kn-affil= en-keyword=chromosome-level genome assembly kn-keyword=chromosome-level genome assembly en-keyword=genome evolution kn-keyword=genome evolution en-keyword=Hi?C scaffolding kn-keyword=Hi?C scaffolding en-keyword=long-read sequencing kn-keyword=long-read sequencing en-keyword=non-model animals kn-keyword=non-model animals END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=8 article-no= start-page=117125 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=Brain circadian clock neurons drive fitness advantages in Drosophila en-subtitle= kn-subtitle= en-abstract= kn-abstract=The adaptive significance of circadian clocks is widely assumed due to their ubiquity; yet, direct empirical evidence remains scarce. Evaluating these benefits is often confounded by pleiotropic effects in conventional circadian null mutants. To address this, we selectively altered the circadian period exclusively within brain clock neurons in Drosophila melanogaster. Multi-generational competition assays revealed that flies with aberrant rhythms exhibit a significant fitness disadvantage under standard light-dark (LD 12:12) cycles. This disadvantage was abolished under constant light, confirming that the selection pressure is specifically mediated by the circadian clock. Furthermore, paternity assays conducted under LD 12:12 indicated that the timing of brain clock neurons influences male reproductive success, providing a potential mechanistic link between clock-controlled behavior and fitness. Intriguingly, we found that these fitness costs are highly photoperiod-dependent. Under short-day conditions (LD 8:16), the short-period strain (dbtS) maintained a significantly higher overall frequency than the long-period strain (dbtL). Our behavioral observations suggest that this difference may be associated with the quality of activity rhythms; specifically, dbtS lacked defined morning peaks and showed suppressed nocturnal activity, potentially narrowing its window for reproductive interactions compared to dbtL. These findings illustrate that the circadian system does not merely track a 24-h cycle but functions as a flexible feature that enables flies to cope with changing day lengths by aligning their mating behavior with the most favorable time of day. en-copyright= kn-copyright= en-aut-name=AikawaSae en-aut-sei=Aikawa en-aut-mei=Sae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TamuraShoichiro en-aut-sei=Tamura en-aut-mei=Shoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MimuraMakiko en-aut-sei=Mimura en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshiiTaishi en-aut-sei=Yoshii en-aut-mei=Taishi 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=activity rhythms kn-keyword=activity rhythms en-keyword=clock neurons kn-keyword=clock neurons en-keyword=Drosophila kn-keyword=Drosophila en-keyword=adaptive advantage kn-keyword=adaptive advantage en-keyword=reproductive success kn-keyword=reproductive success en-keyword=resonance hypothesis kn-keyword=resonance hypothesis END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=12 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260707 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Knockout analysis of period and timeless and EGFP-based visualization of per-expressing clock cells in the cricket circadian clock en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the present study, we generated crickets with knockout of either period (per) or timeless (tim) gene by CRISPR/Cas9-based genome editing. We also identified a naturally occurring per- mutant lacking a large coding region including PAS domains. To examine possible synergistic effects, a per- and timKO double mutant was generated by applying genome editing to the per- crickets. Under constant darkness (DD), timKO crickets exhibited a locomotor rhythm with a free-running period of 23.06?±?0.20?h (mean?±?SD), which was significantly shorter than that of the parental strain (23.78?±?0.12?h). By contrast, perKO and per- crickets showed basically similar phenotype of locomotor rhythm: they exhibited an arrhythmic pattern during the first two to three weeks after transfer to DD but subsequently showed a complex rhythmic pattern with one or multiple components with significantly longer free-running periods (33.35?±?10.72?h). In the per-;timKO double mutants, approximately 60% of individuals became arrhythmic, while the remaining 40% exhibited complex rhythms with extremely longer free-running periods (37.0?±?9.17?h) under DD. These results suggest the existence of an underlying oscillatory mechanism that is responsible for regulating locomotor rhythms independently of the canonical per/tim feedback loop. Furthermore, we generated a reporter line on a per? background by knocking egfp into exon 1 of the per gene, allowing egfp expression to report per transcription. EGFP expression was detected in three distinct clusters of cells within the optic lobe: two located along the dorsal and ventral boundaries between the lamina and medulla neuropils, and one situated near the accessory medulla. These findings raise the possibility that these form part of the circadian clock network that governs circadian locomotor rhythms. en-copyright= kn-copyright= en-aut-name=TomiokaKenji en-aut-sei=Tomioka en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueShintaro en-aut-sei=Inoue en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitoTaro en-aut-sei=Mito en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriyamaYoshiyuki en-aut-sei=Moriyama en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshiiTaishi en-aut-sei=Yoshii en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Bio-Innovation Research Center, Tokushima University kn-affil= affil-num=3 en-affil=Bio-Innovation Research Center, Tokushima University kn-affil= affil-num=4 en-affil=Department of Natural Sciences, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Circadian clock kn-keyword=Circadian clock en-keyword=Cricket kn-keyword=Cricket en-keyword=Genome editing kn-keyword=Genome editing en-keyword=Locomotor rhythm kn-keyword=Locomotor rhythm en-keyword=period kn-keyword=period en-keyword=per-less oscillation kn-keyword=per-less oscillation en-keyword=timeless kn-keyword=timeless 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=20260819 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Micro-segregation of Primary Si in ADC14 (Al?17Si?4Cu) Alloy Produced by Unidirectional Continuous Casting en-subtitle= kn-subtitle= en-abstract= kn-abstract=An upgrading approach for hypereutectic Al?Si alloys was investigated through controlled segregation of Si using a unidirectional casting process. The precipitation behavior and spatial distribution of primary Si in the hypereutectic ADC14 (Al?17Si?4Cu) alloy were systematically examined at different casting speeds (0.06, 1.9, and 10 mm/s). Microstructural observations revealed that high casting speed suppresses primary Si formation due to rapid solidification, whereas intermediate speed leads to a relatively uniform distribution of primary Si. In contrast, low casting speed combined with a holding period for 2 min promotes pronounced segregation and coarsening of primary Si in localized regions. Energy-dispersive X-ray spectroscopy analysis confirmed significant fluctuations in Si concentration along the casting direction, particularly after process interruption. Based on these results, a preliminary upgrading process was proposed, involving the selective removal of Si-enriched regions followed by remelting. This approach resulted in a reduction of Si content to approximately 13.9 wt.%, corresponding to a decrease of about 3%. The results demonstrate that controlling solidification behavior to induce phase separation provides a promising and energy-efficient strategy for upgrading recycled Al?Si alloys. en-copyright= kn-copyright= en-aut-name=TakeuchiShuhei en-aut-sei=Takeuchi en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakagawaShota en-aut-sei=Nakagawa en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShinzatoYoshifumi en-aut-sei=Shinzato en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MinodaTadashi en-aut-sei=Minoda en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtsukaNaotaka en-aut-sei=Ohtsuka en-aut-mei=Naotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkayasuMitsuhiro en-aut-sei=Okayasu en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=UACJ Corporation kn-affil= affil-num=3 en-affil=UACJ Corporation kn-affil= affil-num=4 en-affil=UACJ Corporation kn-affil= affil-num=5 en-affil=UACJ Corporation kn-affil= affil-num=6 en-affil=Department of Mechanical and Systems Engineering, Okayama University kn-affil= en-keyword=upgrading technique kn-keyword=upgrading technique en-keyword=Al?Si alloy kn-keyword=Al?Si alloy en-keyword=primary Si kn-keyword=primary Si en-keyword=segregation kn-keyword=segregation en-keyword=unidirectional solidification kn-keyword=unidirectional solidification END start-ver=1.4 cd-journal=joma no-vol=127 cd-vols= no-issue=3 article-no= start-page=e71081 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=AHG1?AFP interaction as a regulatory node in the ABA response during seed germination en-subtitle= kn-subtitle= en-abstract= kn-abstract=Seed dormancy and germination are tightly regulated by complex signaling networks that integrate internal and external cues, including the endogenous phytohormone abscisic acid (ABA). ABA HYPERSENSITIVE GERMINATION 1 (AHG1), a group A type 2C protein phosphatase (PP2C), is thought to modulate the activity of transcription factors such as ABA INSENSITIVE 5 (ABI5) in seeds and during germination. AHG1 is regulated by DELAY OF GERMINATION 1 (DOG1), a key regulator of seed dormancy, through physical interaction. We previously reported that AHG1 also interacts with ABI FIVE BINDING PROTEIN 2 (AFP2), a member of the AFP family; however, the molecular basis of AHG1?AFP coordination has remained unclear. In this study, we show that AHG1 interacts with all AFP family members and that AFP3 binds AHG1 and ABI5 through adjacent but distinct amino acid residues within its C-domain, allowing simultaneous association with both proteins. In addition, AHG1 modulates the phosphorylation status of AFP3 at Ser60 in a DOG1-dependent manner, suggesting that DOG1?AHG1 regulates AFP3 post-translationally. Transcriptomic analyses of AHG1- or AFP3-overexpressing lines revealed that these factors are associated with the regulation of a shared set of ABA-responsive genes, including AFPs, and that AFP3 overexpression is predominantly associated with altered expression of genes involved in transcriptional regulation. Large-scale protein interaction analyses showed that AFPs interact with multiple classes of transcription factors, suggesting their involvement in diverse regulatory pathways, including ABA signaling. Together, these findings demonstrate that DOG1 regulates ABI5 function and modulates ABA responses, at least in part, by controlling AHG1-mediated dephosphorylation of AFPs. en-copyright= kn-copyright= en-aut-name=NishimuraNoriyuki en-aut-sei=Nishimura en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UshiyamaSho en-aut-sei=Ushiyama en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtagiriMasato en-aut-sei=Otagiri en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatohKouji en-aut-sei=Satoh en-aut-mei=Kouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiNahomi en-aut-sei=Suzuki en-aut-mei=Nahomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IrisaTomoko en-aut-sei=Irisa en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MitsudaNobutaka en-aut-sei=Mitsuda en-aut-mei=Nobutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UmezawaTaishi en-aut-sei=Umezawa en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishimuraHideki en-aut-sei=Nishimura en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NemotoKeiichirou en-aut-sei=Nemoto en-aut-mei=Keiichirou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsuchiyaWataru en-aut-sei=Tsuchiya en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YanoRyoichi en-aut-sei=Yano en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SawasakiTatsuya en-aut-sei=Sawasaki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamazakiToshimasa en-aut-sei=Yamazaki en-aut-mei=Toshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HirayamaTakashi en-aut-sei=Hirayama en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Institute of Agrobiological Sciences, National Agriculture and Food Research Organization 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 Agrobiological Sciences, National Agriculture and Food Research Organization kn-affil= affil-num=5 en-affil=Institute of Agrobiological Sciences, National Agriculture and Food Research Organization kn-affil= affil-num=6 en-affil=Institute of Agrobiological Sciences, National Agriculture and Food Research Organization kn-affil= affil-num=7 en-affil=Biomanufacturing Process Research Center, National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=8 en-affil=Graduate School of Advanced Interdisciplinary Science, Tokyo University of Agriculture and Technology kn-affil= affil-num=9 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=10 en-affil=Proteo-Science Center, PIAS, Ehime University kn-affil= affil-num=11 en-affil=Research Center for Advanced Analysis, National Agriculture and Food Research Organization kn-affil= affil-num=12 en-affil=Research Center for Advanced Analysis, National Agriculture and Food Research Organization kn-affil= affil-num=13 en-affil=Proteo-Science Center, PIAS, Ehime University kn-affil= affil-num=14 en-affil=Research Center for Advanced Analysis National Agriculture and Food Research Organization Tsukuba Ibaraki 305‐8518 Japan kn-affil= affil-num=15 en-affil=Research Center for Advanced Analysis, National Agriculture and Food Research Organization kn-affil= en-keyword=ABA kn-keyword=ABA en-keyword=AHG1 kn-keyword=AHG1 en-keyword=AFP kn-keyword=AFP en-keyword=ABI5 kn-keyword=ABI5 en-keyword=DOG1 kn-keyword=DOG1 en-keyword=seed dormancy kn-keyword=seed dormancy en-keyword=seed germination kn-keyword=seed germination en-keyword=Arabidopsis thaliana kn-keyword=Arabidopsis thaliana END start-ver=1.4 cd-journal=joma no-vol=384 cd-vols= no-issue= article-no= start-page=114996 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alternative transcription of the mouse Gh gene identifies an immune-associated transcript with species-specific structural divergence en-subtitle= kn-subtitle= en-abstract= kn-abstract=Growth hormone (GH) in mice is primarily expressed in the anterior pituitary, although Gh expression has been reported in extrapituitary tissues, including immune organs. However, the structure of immune-associated Gh transcripts remains poorly characterized. To determine whether splenic Gh transcripts differ from pituitary Gh mRNA, 5′- and 3′-rapid amplification of cDNA ends (RACE) analyses were performed. While 3′ RACE showed a shared polyadenylation site, 5′ RACE identified a novel exon located approximately 2 kb upstream of the conventional exon 1, generating a transcript (spl-Gh mRNA) with a distinct first exon but shared downstream exons with pituitary Gh mRNA (pit-Gh mRNA). RT-PCR analysis revealed that spl-Gh mRNA is predominantly expressed in immune tissues such as spleen and bone marrow, and its distribution did not correlate with Pit-1 mRNA expression. Quantitative RT-PCR further demonstrated that spl-Gh mRNA was expressed at levels comparable to those of pit-Gh mRNA in the mouse spleen, indicating that spl-Gh is one of the major Gh transcript forms in this tissue. Sequence analysis indicated that spl-Gh mRNA is predicted to retain coding potential for a GH protein. Comparative genomic analyses further demonstrated that genomic features associated with the spl-Gh transcriptional unit are conserved only in a subset of closely related Mus species. In contrast, although a spl-Gh?related transcript was detected in rat spleen, no properly spliced mouse-like transcript was identified under the present experimental conditions. The detected transcript exhibited intron retention and an in-frame stop codon, suggesting that it is unlikely to produce a functional GH protein. These findings identify a distinct immune-associated Gh transcript generated through alternative transcription of the mouse Gh gene and suggest that immune-associated Gh transcriptional mechanisms have undergone species-specific divergence among rodents. Together, these findings reveal previously unrecognized complexity in Gh gene regulation and highlight species-specific differences in immune-associated Gh transcripts. en-copyright= kn-copyright= en-aut-name=FukushimaAi en-aut-sei=Fukushima en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeuchiYu en-aut-sei=Takeuchi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukuchiHibiki en-aut-sei=Fukuchi en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EgoshiSakura en-aut-sei=Egoshi en-aut-mei=Sakura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakamotoHirotaka en-aut-sei=Sakamoto en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AizawaSayaka en-aut-sei=Aizawa en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeuchiSakae en-aut-sei=Takeuchi en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of 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= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Growth hormone kn-keyword=Growth hormone en-keyword=Alternative transcription kn-keyword=Alternative transcription en-keyword=Immune-associated transcript kn-keyword=Immune-associated transcript en-keyword=Extrapituitary expression kn-keyword=Extrapituitary expression en-keyword=Species-specific divergence kn-keyword=Species-specific divergence en-keyword=Mouse kn-keyword=Mouse END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=1 article-no= start-page=893 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250607 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural insights into tRNA recognition of the human FTSJ1-THADA complex en-subtitle= kn-subtitle= en-abstract= kn-abstract=tRNA undergoes various post-transcriptional modifications in the anticodon loop. FTSJ1, a protein conserved among most eukaryotes, mediates 2’-O-methylations at position 32 (Nm32) or position 34 (Nm34), complexed with THADA or WDR6, respectively. These methylations are crucial for accurate translation and cellular growth. FTSJ1 mutations are associated with non-syndromic X-linked intellectual disability. Although the structure of the FTSJ1-WDR6 complex in yeast has been solved, the structural details of the FTSJ1-THADA complex formation and substrate recognition remain unclear. Herein, using cryo-electron microscopy, we solve the high-resolution structure of FTSJ1-THADA with or without a tRNA substrate. FTSJ1 binds to THADA via its C-terminal region, with a unique interaction mode distinct from the FTSJ1-WDR6 complex. The tRNA substrate is anchored inside THADA, and key THADA residues for THADA-tRNA interaction are identified via structural and biochemical analyses. These findings demonstrate how FTSJ1 and THADA form a complex to mediate Nm32 modification in various tRNAs. en-copyright= kn-copyright= en-aut-name=IshiguroKensuke en-aut-sei=Ishiguro en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=ShirouzuMikako en-aut-sei=Shirouzu en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research 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=Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research kn-affil= END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=11 article-no= start-page=1302 end-page=1313 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=Trastuzumab-Pertuzumab Plus Eribulin or Taxane as First-Line Chemotherapy for Human Epidermal Growth Factor 2?Positive Locally Advanced/Metastatic Breast Cancer: The Randomized Noninferiority Phase III EMERALD Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Trastuzumab-pertuzumab (HP) plus taxane is a current standard first-line therapy for recurrent or metastatic human epidermal growth factor 2 (HER2)+ breast cancer (BC). We investigated noninferiority of eribulin to a taxane when combined with dual HER2 blockade as first-line systemic treatment for locally advanced/metastatic HER2+ BC.
Methods In the phase III EMERALD trial (target sample size, 480; ClinicalTrials.gov identifier: NCT03264547/UMIN000027938), patients were randomly assigned (1:1) to receive eribulin 1.4 mg/m2 once daily on days 1 and 8 (eribulin group) or a taxane (docetaxel 75 mg/m2 once on day 1 or paclitaxel 80 mg/m2 once daily on days 1, 8, and 15; taxane group) intravenously in a 21-day cycle, each with HP on day 1. The primary end point was progression-free survival (PFS; intention-to-treat population). Secondary end points included objective response rate, overall survival (OS), patient-reported quality of life (QoL), and safety. Noninferiority was tested using the stratified Cox proportional hazards model to estimate hazard ratios (HRs) for PFS events, with a noninferiority HR margin of 1.33.
Results Between August 2017 and June 2021, 446 patients (median age, 56.0 years) were enrolled. The median PFS was 14.0 and 12.9 months in the eribulin group (n = 224) and taxane group (n = 222 [docetaxel/paclitaxel, n = 186/36]), respectively (HR, 0.95 [95% CI, 0.76 to 1.19]), which confirmed the noninferiority of the study regimen. The median OS was 65.3 months in the taxane group but has not been reached in the eribulin group. Median time to QoL deterioration was numerically longer with eribulin than with taxane. Adverse event (AE) rates were similar, despite the longer duration of eribulin use. Infusion reaction, skin-related AEs, diarrhea, and edema were more common with taxane, whereas neutropenia was more common with eribulin.
Conclusion The results suggested that eribulin + HP is an option for first-line treatment of locally advanced/metastatic HER2+ BC. en-copyright= kn-copyright= en-aut-name=YamashitaToshinari en-aut-sei=Yamashita en-aut-mei=Toshinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SajiShigehira en-aut-sei=Saji en-aut-mei=Shigehira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakanoToshimi en-aut-sei=Takano en-aut-mei=Toshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaitoYoichi en-aut-sei=Naito en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuneizumiMichiko en-aut-sei=Tsuneizumi en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshimuraAkiyo en-aut-sei=Yoshimura en-aut-mei=Akiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiMasato en-aut-sei=Takahashi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsurutaniJunji en-aut-sei=Tsurutani en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwataniTsuguo en-aut-sei=Iwatani en-aut-mei=Tsuguo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitadaMasahiro en-aut-sei=Kitada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TadaHiroshi en-aut-sei=Tada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoriNatsuko en-aut-sei=Mori en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HiguchiToru en-aut-sei=Higuchi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwasaTsutomu en-aut-sei=Iwasa en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ArakiKazuhiro en-aut-sei=Araki en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KoizumiKei en-aut-sei=Koizumi en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= en-aut-name=UchidaYohei en-aut-sei=Uchida en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 ORCID= en-aut-name=MasudaNorikazu en-aut-sei=Masuda en-aut-mei=Norikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Breast Surgery and Oncology, Kanagawa Cancer Center kn-affil= affil-num=2 en-affil=Department of Medical Oncology, Fukushima Medical University kn-affil= affil-num=3 en-affil=Department of Breast Medical Oncology, The Cancer Institute Hospital of JFCR kn-affil= affil-num=4 en-affil=Department of General Internal Medicine, National Cancer Center Hospital East kn-affil= affil-num=5 en-affil=Department of Breast Surgery, Shizuoka General Hospital 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 Surgery, Hokkaido University Hospital kn-affil= affil-num=8 en-affil=Advanced Cancer Translational Research Institute, Showa University kn-affil= affil-num=9 en-affil=Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Breast Disease Center, Asahikawa Medical University Hospital kn-affil= affil-num=11 en-affil=Department of Surgery, Division of Breast and Endocrine Surgery, Tohoku University Hospital kn-affil= affil-num=12 en-affil=Department of Breast Surgery, Seirei Hamamatsu General Hospital kn-affil= affil-num=13 en-affil=Department of Breast Unit, Japanese Red Cross Saitama Hospital kn-affil= affil-num=14 en-affil=Department of Medical Oncology, Kindai University Hospital kn-affil= affil-num=15 en-affil=Department of Breast Medical Oncology, Gunma Prefectural Cancer Center kn-affil= affil-num=16 en-affil=Department of Surgery 1, Division of Breast Surgery, Hamamatsu University School of Medicine kn-affil= affil-num=17 en-affil=Medical HQs, Eisai Co, Ltd kn-affil= affil-num=18 en-affil=Medical HQs, Eisai Co, Ltd kn-affil= affil-num=19 en-affil=Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University kn-affil= affil-num=20 en-affil=Department of Breast Surgery, Graduate School of Medicine, Kyoto University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=3 article-no= start-page=193 end-page=195 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202405 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hormonal changes revealed by selective arterial calcium injection tests in patients with insulinoma treated with EUS?guided ethanol injection en-subtitle= kn-subtitle= en-abstract= kn-abstract= 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=KomatsubaraMotoshi en-aut-sei=Komatsubara en-aut-mei=Motoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InagakiKenichi en-aut-sei=Inagaki en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=OtukaMotoyuki en-aut-sei=Otuka 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 Hospital kn-affil= affil-num=2 en-affil=Department of Endocrinology, Okayama City Hospital 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 Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=12 article-no= start-page=1227 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240620 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Toloese Generates Nitric Oxide through Natural Radiation of Far Infrared Rays, Reducing Serum Glucose, Cholesterol, and Triglycerides en-subtitle= kn-subtitle= en-abstract= kn-abstract=Toloese, a bed composition, is formulated with a combination of minerals of various wavelengths by utilizing a specific ratio and particle size. A maturation mixing technique is used without additional compression processes, resulting in the natural formation of numerous fine pores in the bed structure. At 40 °C, far infrared radiation in the range of 5?20 μm is emitted with a 0.916 radiant ratio, and the measured emitted radiant energy is 3.69 × 102 W/m2?μm. This study aimed to investigate the influence of far infrared radiation emitted from a Toloese bed on endogenous nitric oxide production. Clinical trials were conducted with 20 healthy adults aged 20 years. Blood samples were collected before and after Toloese bed usage for 1 h daily for 3 weeks. Nitric oxide levels in the saliva and blood of men and women significant increased after they used the Toloese bed for 1 h. Additionally, sweating sharply increased in the upper and lower body regions after Toloese bed usage. No hematological changes or adverse effects were observed, but blood glucose, cholesterol, and triglycerides decreased after Toloese bed usage compared with those before Toloese bed usage. These findings demonstrated that far infrared radiation emitted by the Toloese bed induced endogenous nitric oxide production and contributed to significant reductions in blood glucose, cholesterol, and triglyceride levels. en-copyright= kn-copyright= en-aut-name=YeoMin-Ho en-aut-sei=Yeo en-aut-mei=Min-Ho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LeeYoung-Hyeon en-aut-sei=Lee en-aut-mei=Young-Hyeon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RyuMi-Jin en-aut-sei=Ryu en-aut-mei=Mi-Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChoiYong-Hak en-aut-sei=Choi en-aut-mei=Yong-Hak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimHye-Sook en-aut-sei=Kim en-aut-mei=Hye-Sook kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ChangKyung-Soo en-aut-sei=Chang en-aut-mei=Kyung-Soo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=2 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=3 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=4 en-affil=SayM Co., Ltd. kn-affil= affil-num=5 en-affil=Division of International Infectious Diseases Control, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= en-keyword=Toloese kn-keyword=Toloese en-keyword=far infrared ray kn-keyword=far infrared ray en-keyword=nitric oxide kn-keyword=nitric oxide END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=13203 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Amyloid-forming property of the N-terminal 1?70 residues of human apolipoprotein A-IV en-subtitle= kn-subtitle= en-abstract= kn-abstract=Apolipoprotein A-IV (apoA-IV), the largest member of the exchangeable apolipoprotein family, is a common constituent of amyloid deposits in renal and cardiac amyloidosis. In this study, we characterized the aggregation propensity of the apoA-IV N-terminal fragment to form amyloid fibrils using a variety of biophysical techniques. Thioflavin T fluorescence assay, circular dichroism measurement, and microscopic observations revealed that the N-terminal 1?70 amino acid fragment of apoA-IV readily forms amyloid fibrils by a transition from a random coil to a β-sheet-rich structure. Sequence-based analysis indicated that residues 7?16 and 38?42 are the major aggregation-prone segments within the N-terminal 1?70 residues of apoA-IV. Consistent with this, deletion of these residues strongly inhibited the β-transition and fibril formation of apoA-IV 1?70. Kinetic and thermodynamic analyses of fibril formation by the apoA-IV 1?70 fragment demonstrated that primary nucleation is the dominant step in fibril formation, for which the activation energy barrier is entirely entropic. In addition, we found that the presence of heparin, a representative glycosaminoglycan, accelerated fibril formation kinetics and enhanced the yield of apoA-IV 1?70 fibrils, and the positively charged residues K58-K59 play a critical role in heparin interaction. Overall, our results suggest that the strong amyloid-forming propensity of the N-terminal fragment of apoA-IV may play a key role in amyloid deposition associated with apoA-IV amyloidosis. en-copyright= kn-copyright= en-aut-name=NambaNorihiro en-aut-sei=Namba en-aut-mei=Norihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DanjoTokiko en-aut-sei=Danjo en-aut-mei=Tokiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitagawaYuichiro en-aut-sei=Kitagawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaitoYoshito en-aut-sei=Naito en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhgitaTakashi en-aut-sei=Ohgita en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimanouchiToshinori en-aut-sei=Shimanouchi en-aut-mei=Toshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaitoHiroyuki en-aut-sei=Saito en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University kn-affil= affil-num=2 en-affil=Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University kn-affil= affil-num=3 en-affil=Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University kn-affil= affil-num=4 en-affil=Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University kn-affil= affil-num=5 en-affil=Center for Instrumental Analysis, Kyoto Pharmaceutical University kn-affil= affil-num=6 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University kn-affil= en-keyword=Apolipoprotein A-IV kn-keyword=Apolipoprotein A-IV en-keyword=Aggregation kn-keyword=Aggregation en-keyword=Amyloid fibril kn-keyword=Amyloid fibril en-keyword=Heparin kn-keyword=Heparin END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue= article-no= start-page=1680076 end-page= 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=Prolonged TNF-α stimulation induces a PD-1?associated exhaustion-like phenotype in mesenchymal stromal cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mesenchymal stromal cells (MSCs) have emerged as promising therapeutic agents for inflammatory diseases because of their potent immunomodulatory properties. Although acute inflammation transiently enhances MSC functionality, the impact of chronic inflammatory exposure remains poorly defined. In this study, we investigated the effects of sustained TNF-α stimulation and indirect co-culture with M1 macrophages on MSC behavior. Comprehensive gene expression profiling was performed to assess the changes in immunoregulatory, apoptotic, and metabolic pathways. To determine functional reversibility, we also evaluated MSCs following the withdrawal of TNF-α. Short-term exposure led to upregulation of Tgf-β, Il-10, and Fasl, whereas prolonged stimulation suppressed these genes and significantly increased the expression of immune checkpoint genes Pd-1 and Ctla-4, indicative of an exhaustion-like phenotype. This phenotypic shift was associated with sustained NF-κB activation, upregulation of Stat3 and Ap-1, suppression of mTORC1/2 components, decreased Pd-l1 expression, and increased Pd-1 expression, raising the possibility that PD-1 upregulation is associated with MSC dysfunction under chronic inflammatory stress. These findings revealed that prolonged stimulation (48 h) induces an exhaustion-like dysfunction state in MSCs, characterized by checkpoint activation, transcriptional repression, and metabolic dysfunction. PD-1 may serve as a biomarker associated with inflammation-induced MSC impairment. en-copyright= kn-copyright= en-aut-name=MatsunagaNaoya en-aut-sei=Matsunaga en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkiyamaKentaro en-aut-sei=Akiyama en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MunAung Ye en-aut-sei=Mun en-aut-mei=Aung Ye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZouTinling en-aut-sei=Zou en-aut-mei=Tinling kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItoKazuki en-aut-sei=Ito en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TagashiraRuji en-aut-sei=Tagashira en-aut-mei=Ruji 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= 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 Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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= en-keyword=immune checkpoint kn-keyword=immune checkpoint en-keyword=immunoregulatory dysfunction kn-keyword=immunoregulatory dysfunction en-keyword=mesenchymal stromal cells (MSCs) kn-keyword=mesenchymal stromal cells (MSCs) en-keyword=prolonged inflammatory stimulation kn-keyword=prolonged inflammatory stimulation en-keyword=TNF-α (tumor necrosis factor-alpha) kn-keyword=TNF-α (tumor necrosis factor-alpha) 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=20260625 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of Critical Amino Acid Residues Required for the Polar Localization of a Rice Manganese Transporter en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rice has developed an efficient system for manganese (Mn) uptake, mediated by two distinct transporters, OsNramp5 and OsMTP9. These transporters exhibit polar localization at the root exodermis and endodermis; however, the mechanisms underlying their polar localization and their role in Mn uptake remain unclear. Here, we identified key amino acid residues critical for the polar localization of OsNramp5 at the distal side. Through analysis of chimeric proteins between OsNramp5 and its non-polar homologues, we found that the C-terminal cytosolic region of OsNramp5 is essential for its polar localization. Site-directed mutagenesis further revealed that aspartate 500 and four valine residues at positions 494, 495, 498 and 506 are crucial for polarity. Substitution of these valine residues with isoleucine, leucine, phenylalanine, or threonine partially or fully maintained polar localization, whereas substitution with alanine, serine, or asparagine resulted in loss of polarity. These findings suggest that β-branching and high hydrophobicity of amino acid side chains are likely required for OsNramp5 polarity. Furthermore, we found that adaptor protein 2-dependent clathrin-mediated endocytosis is not involved in the polar localization of OsNramp5. Finally, we provided experimental evidence showing the significant role of OsNramp5 polarity in efficient Mn uptake in rice; plants expressing non-polarly localized OsNramp5 exhibited reduced Mn uptake compared to those with polarly localized OsNramp5. In addition, we found that cadmium accumulation in shoots could be reduced by manipulating OsNramp5 polarity in combination with its overexpression, without a growth penalty. en-copyright= kn-copyright= en-aut-name=KonishiNoriyuki en-aut-sei=Konishi en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaJian Feng en-aut-sei=Ma en-aut-mei=Jian Feng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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= en-keyword=amino acid residue kn-keyword=amino acid residue en-keyword=clathrin-mediated endocytosis kn-keyword=clathrin-mediated endocytosis en-keyword=Mn kn-keyword=Mn en-keyword=OsNramp5 kn-keyword=OsNramp5 en-keyword=polar localization kn-keyword=polar localization en-keyword=rice kn-keyword=rice en-keyword=root kn-keyword=root en-keyword=transporter kn-keyword=transporter END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=180 end-page=186 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250624 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy and Safety of Three Janus Kinase Inhibitors in Ulcerative Colitis Patients over and under 65 Years of Age: A Real-World Comparative Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: It remains unclear whether Janus kinase (JAK) inhibitors differ in efficacy and safety between elderly and non-elderly patients with ulcerative colitis. Methods: We retrospectively compared outcomes between patients who started a JAK inhibitor at ?65 years (elderly group) and those <65 years (non-elderly group). Results: Among 228, 215, and 159 patients treated with upadacitinib, filgotinib, and tofacitinib, we identified 14, 36, and 13 elderly patients, respectively. There were no significant differences in efficacy between elderly and non-elderly patients for any of the three JAK inhibitors. The elderly group had a 3-fold higher risk of herpes zoster infection with upadacitinib or tofacitinib compared to the non-elderly group, whereas the risk with filgotinib was less than 3% in both groups. The non-elderly group had a 3-fold higher risk of acne with upadacitinib. Conclusion: Adverse event risks with JAK inhibitors should be considered by age. Given the limitations of this study, including its retrospective design and small sample size, further studies with larger sample sizes are needed to validate our findings. en-copyright= kn-copyright= en-aut-name=AkiyamaShintaro en-aut-sei=Akiyama en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimizuHiromichi en-aut-sei=Shimizu en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TamuraAkiko en-aut-sei=Tamura en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YokoyamaKaoru en-aut-sei=Yokoyama en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakuraiToshiyuki en-aut-sei=Sakurai en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiMariko en-aut-sei=Kobayashi en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EizukaMakoto en-aut-sei=Eizuka en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YanaiShunichi en-aut-sei=Yanai en-aut-mei=Shunichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NomuraKei en-aut-sei=Nomura en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShibuyaTomoyoshi en-aut-sei=Shibuya en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakaharaMasahiro en-aut-sei=Takahara en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SakoMinako en-aut-sei=Sako en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=TsurutaKozo en-aut-sei=Tsuruta en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YoshiokaShinichiro en-aut-sei=Yoshioka en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KorokuMiki en-aut-sei=Koroku en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OmoriTeppei en-aut-sei=Omori en-aut-mei=Teppei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SarutaMasayuki en-aut-sei=Saruta en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MatsumotoTakayuki en-aut-sei=Matsumoto en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=OkamotoRyuichi en-aut-sei=Okamoto en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=TsuchiyaKiichiro en-aut-sei=Tsuchiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Gastroenterology, Institute of Medicine, University of Tsukuba kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=5 en-affil=Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Institute of Medicine, University of Tsukuba kn-affil= affil-num=7 en-affil=Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University kn-affil= affil-num=8 en-affil=Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University kn-affil= affil-num=9 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=10 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Center for Inflammatory Bowel Disease, Tokyo Yamate Medical Center, Japan Community Healthcare Organization kn-affil= affil-num=14 en-affil=Center for Gastroenterology and Inflammatory Bowel Disease, Ofuna Chuo Hospital kn-affil= affil-num=15 en-affil=Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine kn-affil= affil-num=16 en-affil=Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine kn-affil= affil-num=17 en-affil=Institute of Gastroenterology, Tokyo Women’s Medical University kn-affil= affil-num=18 en-affil=Institute of Gastroenterology, Tokyo Women’s Medical University kn-affil= affil-num=19 en-affil=Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine kn-affil= affil-num=20 en-affil=Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University kn-affil= affil-num=21 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=22 en-affil=Department of Gastroenterology, Institute of Medicine, University of Tsukuba kn-affil= affil-num=23 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= en-keyword=Elderly kn-keyword=Elderly en-keyword=Janus kinase inhibitors kn-keyword=Janus kinase inhibitors en-keyword=Ulcerative colitis kn-keyword=Ulcerative colitis END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue= article-no= start-page=122947 end-page=122962 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=A Novel Approximate Solution Method for Euclidean Steiner Tree Problem Based on Genetic Algorithm en-subtitle= kn-subtitle= en-abstract= kn-abstract=A novel approximate solution method for the Euclidean Steiner tree problem is proposed and its performance is demonstrated through experiments using 195 benchmark problem instances from the OR-Library. Given a finite number of terminal points, the proposed method first generates non-terminal points around each terminal point and at the same location as the Steiner point for each triangle obtained by the Delaunay triangulation for all terminal points. It next runs a genetic algorithm to select a subset of the generated non-terminal points, aiming to minimize the total edge length of a minimum spanning tree for all the terminal points and the selected non-terminal points. It then optimizes the locations of the non-terminal points in the tree using Weiszfeld’s method, while preserving the topology. It finally refines the tree by adding new non-terminal points, adding and removing edges, and optimizing the locations of all non-terminal points. The experimental results show that, among 150 benchmark problem instances with known optimal solutions, the proposed method successfully constructs a Euclidean Steiner tree for 61 instances. For the remaining 89 instances, it produces an approximate solution whose total edge lengths is less than 100.7% of the optimal. The experimental results also show that the proposed method obtains approximate solutions efficiently: within 1.5 seconds for instances with up to 100 terminal points and within 61 seconds for instances with up to 1,000 terminal points. en-copyright= kn-copyright= en-aut-name=ZhangLiping en-aut-sei=Zhang en-aut-mei=Liping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MigitaTsuyoshi en-aut-sei=Migita en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiNorikazu en-aut-sei=Takahashi en-aut-mei=Norikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Combinatorial optimization kn-keyword=Combinatorial optimization en-keyword=genetic algorithm kn-keyword=genetic algorithm en-keyword=Fermat problem kn-keyword=Fermat problem en-keyword=Weiszfeld’s method kn-keyword=Weiszfeld’s method en-keyword=Delaunay triangulation kn-keyword=Delaunay triangulation END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue=1 article-no= start-page=97 end-page=112 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vaccination in paediatric, adolescent, and transitional-age rheumatic diseases: a systematic review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: This systematic review evaluated the efficacy and safety of vaccination in patients with paediatric, adolescent, and transitional-age rheumatic diseases as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement.
Methods: An independent investigator systematically searched PubMed to identify relevant studies published by September 2022. The search results were divided into vaccines or toxoids for diphtheria, pertussis, tetanus, pneumococcus, influenza virus, hepatitis A virus, hepatitis B virus, human papillomavirus, poliovirus, measles virus, mumps virus, rubella virus, varicella zoster virus, and tuberculosis.
Results: A meta-analysis was not feasible due to the lack of randomized controlled trials with standardized patient backgrounds and conditions. Non-live vaccines are generally immunogenic and safe for patients with rheumatic diseases. In contrast, live attenuated vaccines should usually be withheld in patients on immunosuppressants, corticosteroids, biologics, or Janus kinase inhibitors. However, for necessary immunizations against measles, rubella, mumps, or varicella, live attenuated vaccines may be considered for patients receiving low-dose corticosteroids, methotrexate, or tumour necrosis factor inhibitors.
Conclusions This review highlights the significant gap in evidence for paediatric populations compared with adults, particularly concerning new biological therapies and Janus kinase inhibitors. Further evidence is needed regarding vaccination in paediatric patients with rheumatic diseases. en-copyright= kn-copyright= en-aut-name=OhnishiTakuma en-aut-sei=Ohnishi en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=IshimoriShingo en-aut-sei=Ishimori en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=YamazakiSusumu en-aut-sei=Yamazaki en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkafujiIkuo en-aut-sei=Okafuji en-aut-mei=Ikuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhtomoYoshiyuki en-aut-sei=Ohtomo en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KobayashiIchiro en-aut-sei=Kobayashi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pediatrics, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Pediatrics, Kobe University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Faculty of Medical Sciences, Department of Pediatrics, University of Fukui kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Pediatrics, Kobe City Medical Center General Hospital kn-affil= affil-num=8 en-affil=Department of Pediatrics, Juntendo University Nerima Hospital kn-affil= affil-num=9 en-affil=Center for Pediatric Allergy and Rheumatology, KKR Sapporo Medical Center kn-affil= en-keyword=Bacille Calmette?Gu?rin kn-keyword=Bacille Calmette?Gu?rin en-keyword=diphtheria, pertussis, and tetanus vaccine kn-keyword=diphtheria, pertussis, and tetanus vaccine en-keyword=hepatitis A virus vaccine kn-keyword=hepatitis A virus vaccine en-keyword=hepatitis B virus vaccine kn-keyword=hepatitis B virus vaccine en-keyword=human papillomavirus vaccine kn-keyword=human papillomavirus vaccine en-keyword=inactivated polio vaccine kn-keyword=inactivated polio vaccine en-keyword=influenza vaccine kn-keyword=influenza vaccine en-keyword=measles, mumps, and rubella vaccine kn-keyword=measles, mumps, and rubella vaccine en-keyword=pneumococcal vaccine kn-keyword=pneumococcal vaccine en-keyword=varicella zoster virus vaccine kn-keyword=varicella zoster virus vaccine END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue=2 article-no= start-page=159 end-page=169 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260811 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An interdisciplinary approach to sampling hard rock cores of the oceanic crust for microbiological and biogeochemical research en-subtitle= kn-subtitle= en-abstract= kn-abstract=Studying life in the deep, rocky subseafloor involves many layers of technological and methodological challenges, and each drilling project or expedition must make a series of choices to address these challenges. We report on the workflow for sampling hard rock cores for microbiological and biogeochemical research that was developed and optimized during International Ocean Discovery Program (IODP) Expedition 399. All steps of the workflow, including selection of the sample and its shipboard homogenization and subsampling for specific analyses, were designed to maximize the potential for interdisciplinary collaborations and syntheses of results. Furthermore, multiple strategies to minimize and detect potential microbial and organic chemical contamination of the core samples were employed, including the shipboard detection of a fluorescent chemical tracer pumped into the drill fluid. Contamination tracer levels were detectable on the exterior surfaces of the core but absent in the homogenized interiors of most core samples. Based on the experiences and preliminary results of this expedition, recommendations for processing samples on future expeditions are presented. en-copyright= kn-copyright= en-aut-name=BrazeltonWilliam J. en-aut-sei=Brazelton en-aut-mei=William J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=CavazosOscar en-aut-sei=Cavazos en-aut-mei=Oscar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RobareJordyn A. en-aut-sei=Robare en-aut-mei=Jordyn A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SouthamGordon en-aut-sei=Southam en-aut-mei=Gordon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuhonenJohanna en-aut-sei=Suhonen en-aut-mei=Johanna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WangFengping en-aut-sei=Wang en-aut-mei=Fengping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LangSusan Q. en-aut-sei=Lang en-aut-mei=Susan Q. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=McCaigAndrew en-aut-sei=McCaig en-aut-mei=Andrew kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BlumPeter en-aut-sei=Blum en-aut-mei=Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AbeNatsue en-aut-sei=Abe en-aut-mei=Natsue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ColtatR?mi en-aut-sei=Coltat en-aut-mei=R?mi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DeansJeremy R. en-aut-sei=Deans en-aut-mei=Jeremy R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=DickersonKristin L. en-aut-sei=Dickerson en-aut-mei=Kristin L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=GodardMarguerite en-aut-sei=Godard en-aut-mei=Marguerite kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=JohnBarbara E. en-aut-sei=John en-aut-mei=Barbara E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KleinFrieder en-aut-sei=Klein en-aut-mei=Frieder kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KuehnRebecca en-aut-sei=Kuehn en-aut-mei=Rebecca kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=LinKuan-Yu en-aut-sei=Lin en-aut-mei=Kuan-Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=LissenbergC. Johan en-aut-sei=Lissenberg en-aut-mei=C. Johan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=LiuHaiyang en-aut-sei=Liu en-aut-mei=Haiyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=LopesEthan L. en-aut-sei=Lopes en-aut-mei=Ethan L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=NozakaToshio en-aut-sei=Nozaka en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=ParsonsAndrew J. en-aut-sei=Parsons en-aut-mei=Andrew J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=PathakVamdev en-aut-sei=Pathak en-aut-mei=Vamdev kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ReaganMark K. en-aut-sei=Reagan en-aut-mei=Mark K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=WheatC. Geoffrey en-aut-sei=Wheat en-aut-mei=C. Geoffrey kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=School of Biological Sciences, University of Utah kn-affil= affil-num=2 en-affil=International Ocean Discovery Program, Texas A&M University kn-affil= affil-num=3 en-affil=School of Molecular Sciences, Arizona State University kn-affil= affil-num=4 en-affil=School of the Environment and Sustainable Minerals Institute, University of Queensland kn-affil= affil-num=5 en-affil=International Ocean Discovery Program, Texas A&M University kn-affil= affil-num=6 en-affil=School of Oceanography, Shanghai Jiao Tong University kn-affil= affil-num=7 en-affil=Dept. of Geol. and Geophys., Woods Hole Oceanographic Institution kn-affil= affil-num=8 en-affil=School of Earth and Environment, University of Leeds kn-affil= affil-num=9 en-affil=International Ocean Discovery Program, Texas A&M University kn-affil= affil-num=10 en-affil=Japan Agency for Marine-Earth Science and Technology kn-affil= affil-num=11 en-affil=ISTO, UMR 7327, Univ. Orleans, CNRS, BRGM, OSUC kn-affil= affil-num=12 en-affil=School of Biological, Environmental, and Earth Sciences, University of Southern Mississippi kn-affil= affil-num=13 en-affil=Dept. of Earth and Planetary Sciences, University of California kn-affil= affil-num=14 en-affil=Geosciences Montpellier, CNRS, University of Montpellier kn-affil= affil-num=15 en-affil=Dept. of Geology and Geophysics, University of Wyoming, Laramie kn-affil= affil-num=16 en-affil=Dept. of Geol. and Geophys., Woods Hole Oceanographic Institution, kn-affil= affil-num=17 en-affil=Institute of Geosciences and Geography, Martin Luther University Halle-Wittenberg kn-affil= affil-num=18 en-affil=Electron Microscopy Core Facility, Purdue University kn-affil= affil-num=19 en-affil=School of Earth and Environmental Sciences, Cardiff University kn-affil= affil-num=20 en-affil=Center of Deep Sea Research, Institute of Oceanology, Chinese Academy of Sciences kn-affil= affil-num=21 en-affil=Dept. of Geophysics, Stanford University kn-affil= affil-num=22 en-affil=Dept. Earth Sciences, Okayama University kn-affil= affil-num=23 en-affil=School of Geography, Earth and Environmental Sciences, University of Plymouth kn-affil= affil-num=24 en-affil=Dept. Geology, Central University of Punjab kn-affil= affil-num=25 en-affil=Dept. of Earth and Environmental Sciences, University of Iowa kn-affil= affil-num=26 en-affil=Global Undersea Research Unit, University of Alaska Fairbanks kn-affil= END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=4 article-no= start-page=265 end-page=270 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=Transcanal Cochlear Implantation Under Endoscopic Guidance with Canal Closure in a Pediatric Patient with CHARGE Syndrome: A Case Report and Surgical Technique en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cochlear implantation (CI) in patients with CHARGE syndrome presents unique surgical challenges due to complex external, middle, and inner ear malformations. We describe the case of a 3-year-old Japanese boy for whom simultaneous transcanal CI under endoscopic guidance and external auditory canal closure were performed. This approach enabled safe electrode placement and resulted in favorable auditory outcomes, representing a potential novel surgical option for CI in patients with CHARGE syndrome. There are few reports of this type of surgical intervention, and the present case highlights the feasibility and clinical benefits of individualized surgical planning for CI in anatomically complex patients. en-copyright= kn-copyright= en-aut-name=YamasakiTakuto en-aut-sei=Yamasaki en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugayaAkiko en-aut-sei=Sugaya en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NaoiYuto en-aut-sei=Naoi en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KariyaShin en-aut-sei=Kariya en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Otolaryngology-Head and Neck Surgery, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=CHARGE syndrome kn-keyword=CHARGE syndrome en-keyword=cochlear implantation kn-keyword=cochlear implantation en-keyword=transcanal approach kn-keyword=transcanal approach en-keyword=temporal bone anomaly kn-keyword=temporal bone anomaly en-keyword=pediatric otologic surgery kn-keyword=pediatric otologic surgery END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=4 article-no= start-page=259 end-page=264 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=Spinous Process Plate Fixation Alone for an AO Spine Osteoporotic Fracture (OF) 5 Diffuse Idiopathic Skeletal Hyperostosis (DISH)-Associated Thoracolumbar Fracture in a Nonagenarian en-subtitle= kn-subtitle= en-abstract= kn-abstract=Diffuse idiopathic skeletal hyperostosis (DISH) predisposes the spine to highly unstable fractures because of long lever-arm biomechanics. Unstable injuries, including AO Spine Osteoporotic Fracture (OF) type 5, are typically treated with long-segment posterior instrumentation; however, pedicle-screw fixation may be infeasible in very elderly patients with severe osteoporosis, critically narrow pedicles, and/or significant comorbidities. A 93-year-old Japanese woman presented with severe back pain without apparent trauma. Computed tomography (CT) revealed a T12 fracture with DISH, classified as OF5. The pedicles were critically narrow (3.7-4.1 mm), and dual-energy X-ray absorptiometry confirmed severe osteoporosis. Because conventional pedicle-screw fixation was considered technically unsafe and excessively invasive, limited posterior stabilization was performed using a single spinous process plate spanning T10-L1. The operative time was 48 min and the estimated blood loss was 10 ml. Immediate postoperative CT confirmed appropriate implant positioning and maintained alignment. At the 1-year follow-up, CT demonstrated solid bony union with preserved alignment and no implant failure; the patient had remained pain-free and ambulatory. This case demonstrates that spinous process-plate fixation can be a minimally invasive salvage option for carefully selected very-elderly patients with DISH when pedicle-screw instrumentation is not feasible. en-copyright= kn-copyright= en-aut-name=YabunoSatoru en-aut-sei=Yabuno en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YunokiMasatoshi en-aut-sei=Yunoki en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakeuchiSaori en-aut-sei=Takeuchi en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirashitaKoji en-aut-sei=Hirashita 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 Neurosurgery, Kagawa Rosai Hospital kn-affil= affil-num=2 en-affil=Department of Neurosurgery, Kagawa Rosai Hospital kn-affil= affil-num=3 en-affil=Department of Neurosurgery, Kagawa Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Neurosurgery, Kagawa Rosai Hospital kn-affil= en-keyword=DISH kn-keyword=DISH en-keyword=vertebral fracture kn-keyword=vertebral fracture en-keyword=osteoporosis kn-keyword=osteoporosis en-keyword=spinous process plate kn-keyword=spinous process plate END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=4 article-no= start-page=241 end-page=246 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=Video-Assisted Thoracoscopic Resection of an Upper Mediastinal Ectopic Parathyroid Adenoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Primary hyperparathyroidism (pHPT) is typically caused by a parathyroid adenoma, although some cases arise from ectopic glands. Accurate preoperative localization is essential for guiding surgical strategy, particularly for mediastinal lesions. We report successful video-assisted thoracoscopic surgery (VATS) for an upper mediastinal parathyroid adenoma. A 68-year-old woman was referred for hypercalcemia during evaluation for recurrent ureteral stones. Laboratory tests revealed elevated serum calcium (13.2 mg/dl) and intact parathyroid hormone (iPTH) levels (266 pg/ml). Contrast-enhanced computed tomography, magnetic resonance imaging, and 99mTc-methoxyisobutylisonitrile scintigraphy identified a 20-mm mass adjacent to the right esophageal wall. VATS was performed due to the tumor’s mediastinal location. The lesion was resected with intraoperative nerve monitoring (IONM) to avoid recurrent laryngeal nerve damage. Postoperatively, iPTH and calcium levels rapidly normalized. Transient hypocalcemia and mild hoarseness occurred but resolved with calcium supplementation and conservative management. Pathological examination confirmed a parathyroid adenoma without malignancy. VATS offers a safe and minimally invasive approach for upper mediastinal parathyroid adenomas. IONM and vigilant calcium management are crucial for minimizing these complications. This case highlights the importance of comprehensive imaging, surgical planning, and postoperative care in managing upper mediastinal pHPT. en-copyright= kn-copyright= en-aut-name=HasegawaYuta en-aut-sei=Hasegawa en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujimotoHironori en-aut-sei=Tsujimoto en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UehataNaoyuki en-aut-sei=Uehata en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KariyaRisa en-aut-sei=Kariya en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IdeAsuma en-aut-sei=Ide en-aut-mei=Asuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiTakafumi en-aut-sei=Suzuki en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujishimaSeiichiro en-aut-sei=Fujishima en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KouzuKeita en-aut-sei=Kouzu en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YaguchiYoshihisa en-aut-sei=Yaguchi en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyaiKosuke en-aut-sei=Miyai en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KuriharaAyumu en-aut-sei=Kurihara en-aut-mei=Ayumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OgataSho en-aut-sei=Ogata en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsukumaSusumu en-aut-sei=Matsukuma en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UenoHideki en-aut-sei=Ueno en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=4 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=6 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=10 en-affil=Department of Laboratory Medicine, National Defense Medical College Hospital kn-affil= affil-num=11 en-affil=Department of Laboratory Medicine, National Defense Medical College Hospital kn-affil= affil-num=12 en-affil=Department of Laboratory Medicine, National Defense Medical College Hospital kn-affil= affil-num=13 en-affil=Department of Laboratory Medicine, National Defense Medical College Hospital kn-affil= affil-num=14 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= en-keyword=primary hyperparathyroidism kn-keyword=primary hyperparathyroidism en-keyword=parathyroid neoplasm kn-keyword=parathyroid neoplasm en-keyword=ectopic tissue kn-keyword=ectopic tissue en-keyword=video-assisted thoracoscopic surgery kn-keyword=video-assisted thoracoscopic surgery END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=4 article-no= start-page=233 end-page=240 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=Regional Prevalence of Carbapenemase-Producing Enterobacterales and Extended-Spectrum Beta-Lactamase-Producing Enterobacterales in Okayama and Neighboring Prefectures, Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Carbapenemase-producing Enterobacterales (CPE) and extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-E) are representative antimicrobial-resistant pathogens. We investigated the prevalence of CPE and ESBL-E in Okayama, Japan to clarify their current epidemiology and potential clinical burden. Active surveillance for CPE and ESBL-E was performed first, using stool samples submitted to the Okayama Medical Laboratory (Japan) in the years 2024-2025. Screening was performed using a selective agar (CHROMagar mSuper CARBA/ESBL). Phenotypic identification was conducted with the use of a modified carbapenem inactivation method and double-disk phenotypic confirmatory tests. Clinical information including patient age, sex, sampling date, and hospital address were collected, and the data were analyzed according to specimen origin (hospitals, clinics, and health checkups). A total of 2,000 stool samples were screened, of which two CPE isolates (0.1%) and 285 ESBL-E isolates (14.3%) were identified. By specimen origin, the ESBL-E positivity rate was significantly higher in hospitals (17.4%) than in clinics (11.8%). By age category, the late elderly (> 75 years) exhibited the highest ESBL-E positivity rate (22.6%) compared to other age groups. In the clinics and health checkups, infants (0 years) demonstrated high ESBL-E positivity rates (18.2% and 14.3%, respectively). Escherichia coli was the most common ESBL-E organism in the hospitals (77.2%), clinics (88.8%), and health checkups (87.5%). Our active screening demonstrated that the prevalences of CPE and ESBL-E were within the reported ranges; however, in this era of increasing internationalization, continuous surveillance of these notifiable pathogens is warranted. en-copyright= kn-copyright= en-aut-name=OgawaSakura en-aut-sei=Ogawa en-aut-mei=Sakura 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=AkazawaHidemasa en-aut-sei=Akazawa en-aut-mei=Hidemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NambaSachie en-aut-sei=Namba en-aut-mei=Sachie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HirotaChiyoko en-aut-sei=Hirota en-aut-mei=Chiyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KishiueTomoyoshi en-aut-sei=Kishiue en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IbaraShohei en-aut-sei=Ibara en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KondoTakayuki en-aut-sei=Kondo en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FukudaGenshi en-aut-sei=Fukuda en-aut-mei=Genshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=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=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi 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= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Laboratory Testing, Okayama Medical Laboratory Center kn-affil= affil-num=5 en-affil=Department of Laboratory Testing, Okayama Medical Laboratory Center kn-affil= affil-num=6 en-affil=Department of Laboratory Testing, Okayama Medical Laboratory Center kn-affil= affil-num=7 en-affil=Department of Laboratory Testing, Okayama Medical Laboratory Center kn-affil= affil-num=8 en-affil=Department of Laboratory Testing, Okayama Medical Laboratory Center kn-affil= affil-num=9 en-affil=Department of Sales Promotion, Okayama Medical Laboratory Center kn-affil= affil-num=10 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=12 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=13 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=antimicrobial resistance kn-keyword=antimicrobial resistance en-keyword=carbapenem-resistant Enterobacteriaceae kn-keyword=carbapenem-resistant Enterobacteriaceae en-keyword=extended-spectrum β-lactamase kn-keyword=extended-spectrum β-lactamase en-keyword=infection prevention and control kn-keyword=infection prevention and control en-keyword=Okayama Medical Laboratory kn-keyword=Okayama Medical Laboratory END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=4 article-no= start-page=227 end-page=231 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=The Impact of Migraine on Cerebral Artery Dissection en-subtitle= kn-subtitle= en-abstract= kn-abstract=The impact of migraines as a risk factor for cervicocerebral artery dissection was retrospectively investigated in patients who had a cervicocerebral artery dissection. We first evaluated the patients’ medical records and history of migraine and then calculated the proportion of patients with migraine as well as the relevant vascular risk factors. The prevalence of migraine with respect to the location of the cervicocerebral artery dissection was also identified. Sixty-two patients (37 men, 25 women) had both a cerebral artery dissection and a record of migraine. Among them, 93.5% presented with an isolated headache, and 6.5% presented with a related stroke. Regarding the locations of the artery dissection, 56 (90.3%) were in the intracranial vertebral artery (VA), three (4.8%) were in the internal carotid artery, and one case each (1.6%) was in an anterior cerebral artery, basilar artery (BA), and both the VA and BA. Among the patients with VA dissection, 42 (73.7%) presented with migraines. Among the four patients with dissection of an artery of anterior circulation, only one (25%) had a migraine history. The frequency of migraines tended to be higher in the patients with VA dissection compared to those with a dissection of arteries of anterior circulation. These data suggest that (i) migraine is a potent risk factor for cerebral artery dissection, especially intracranial VA dissection, and (ii) the intracranial VA may be more susceptible to dissection compared to arteries of anterior circulation. en-copyright= kn-copyright= en-aut-name=KashiharaKenichi en-aut-sei=Kashihara en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamaguchiToshikazu en-aut-sei=Hamaguchi en-aut-mei=Toshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakedaYasuko en-aut-sei=Takeda en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Okayama Neurology Clinic kn-affil= affil-num=2 en-affil=Department of Neurology, Okayama Kyokuto Hospital kn-affil= affil-num=3 en-affil=Okayama Neurology Clinic kn-affil= en-keyword=cervicocerebral artery dissection kn-keyword=cervicocerebral artery dissection en-keyword=isolated headache kn-keyword=isolated headache en-keyword=migraine kn-keyword=migraine en-keyword=risk factor kn-keyword=risk factor en-keyword=vertebral artery kn-keyword=vertebral artery 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=20260711 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical utility of diagnosing Lynch syndrome in gynecologic oncology: a joint statement from four Japanese academic societies en-subtitle= kn-subtitle= en-abstract= kn-abstract=Lynch syndrome (LS) is an autosomal dominant cancer predisposition syndrome, associated with substantially increased risks of colorectal and gynecologic malignancies. Endometrial cancer may serve as a sentinel cancer for LS, placing gynecologists and gynecologic oncologists in a key position for early recognition and long-term management. This joint statement was developed through a multidisciplinary process involving the Japan Society of Gynecologic Oncology, the Japan Society of Clinical Oncology, the Japanese Society of Hereditary Tumors, and the Japanese Society for Cancer of the Colon and Rectum. It aims to clarify the clinical utility of diagnosing LS in gynecologic oncology within the Japanese healthcare system. We outline a tumor-first paradigm in which universal mismatch repair immunohistochemistry and/or microsatellite instability testing for endometrial cancer facilitates LS detection and provides actionable biomarkers for systemic therapy. This statement summarizes the clinical impact of LS diagnosis across gynecologic oncology. We highlight patterns of synchronous and metachronous malignancies and the prevalence of LS in ovarian cancer, particularly in endometrioid and clear?cell subtypes. We discuss surgical implications, including risk-reducing hysterectomy with bilateral salpingo-oophorectomy, consideration of concomitant gynecologic risk-reducing surgery during colorectal cancer resection, and individualized ovarian preservation in selected early-stage endometrial cancer or atypical endometrial hyperplasia. We also review the treatment relevance of deficient mismatch repair/microsatellite instability-high status for immune checkpoint inhibitors and emerging fertility-preserving approaches, and address surveillance, cascade testing for relatives, implementation barriers, and the need for multidisciplinary pathways and healthcare system?level support to ensure equitable access to genetic counseling and testing. en-copyright= kn-copyright= en-aut-name=SatoShinya en-aut-sei=Sato en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MasudaKenta en-aut-sei=Masuda en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OdaKatsutoshi en-aut-sei=Oda en-aut-mei=Katsutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuwataTakeshi en-aut-sei=Kuwata en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakajimaTakeshi en-aut-sei=Nakajima en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamadaMasayoshi en-aut-sei=Yamada en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamaguchiTatsuro en-aut-sei=Yamaguchi en-aut-mei=Tatsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=MandaiMasaki en-aut-sei=Mandai en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakayaKohji en-aut-sei=Tanakaya en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshidaHideyuki en-aut-sei=Ishida en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YoshinoTakayuki en-aut-sei=Yoshino en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkamotoAikou en-aut-sei=Okamoto en-aut-mei=Aikou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Tottori University kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Division of Integrative Genomics, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Genetic Medicine and Services, National Cancer Center Hospital East kn-affil= affil-num=5 en-affil=Division of Hereditary Tumors, Department of Genetic Oncology, Osaka International Cancer Institute kn-affil= affil-num=6 en-affil=Endoscopy Division, National Cancer Center Hospital kn-affil= affil-num=7 en-affil=Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=8 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Surgery, National Hospital Organization Iwakuni Medical Center kn-affil= affil-num=11 en-affil=Department of Clinical Genetics, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East kn-affil= affil-num=13 en-affil=Department of Obstetrics and Gynecology, Sanno Hospital, International University of Health and Welfare kn-affil= en-keyword=Lynch syndrome kn-keyword=Lynch syndrome en-keyword=Endometrial cancer kn-keyword=Endometrial cancer en-keyword=Ovarian cancer kn-keyword=Ovarian cancer en-keyword=Mismatch repair kn-keyword=Mismatch repair en-keyword=Microsatellite instability kn-keyword=Microsatellite instability en-keyword=Immune checkpoint inhibitor kn-keyword=Immune checkpoint inhibitor END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=1 article-no= start-page=552 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260810 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Preoperative membranous urethral length predicts quality-of-life recovery and urinary incontinence after holmium enucleation of the prostate en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Holmium laser enucleation of the prostate (HoLEP) relieves bladder outlet obstruction, but postoperative quality-of-life (QOL) recovery and stress urinary incontinence (SUI) differ among patients. We evaluated whether preoperative membranous urethral length (MUL) on MRI predicts QOL recovery and SUI after HoLEP, independent of clinical and surgical factors.
Methods This single-center retrospective study included 135 patients with preoperative MRI. MUL was measured on sagittal T2-weighted images. The primary outcome was 6-month International Prostate Symptom Score (IPSS) -QOL ? 1. SUI was defined as the use of ?1 pad per day at 6 months. IPSS-QOL changes were analyzed with generalized estimating equations. For 6-month QOL recovery and SUI, logistic regression was adjusted for age, enucleated weight, prostate volume, baseline QOL, and surgeon. We evaluated thickness of posterior wall of membranous urethral sphincter (TPWMUS), membranous urethral volume (MUV), and a short-MUL/thin-TPWMUS phenotype.
Results The 6-month IPSS-QOL ? 1 rate was 40.0%; SUI occurred in 19/135 patients (14.1%). Longer MUL was linked to better QOL recovery at every time point (p ? 0.015) and independently predicted both 6-month QOL recovery (adjusted odds ratio [aOR] 1.35, 95% CI 1.14?1.61) and lower SUI risk (odds ratio [OR] 0.76, 0.61?0.93), remaining significant after adjustment. Adding MUL improved prediction (AUC for SUI 0.588→0.704; for QOL 0.716→0.760). Across MUL tertiles, QOL recovery rose from 13.9% to 56.1% ,and SUI fell from 20.0% to 2.2%. Short MUL/thin-TPWMUS showed higher SUI and poorer QOL recovery.
Conclusions Preoperative MUL on MRI independently predicted QOL recovery and continence after HoLEP. en-copyright= kn-copyright= en-aut-name=NagasakiNaoya en-aut-sei=Nagasaki en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=WatanabeTomofumi en-aut-sei=Watanabe en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanemotoShin en-aut-sei=Kanemoto en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 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=10 ORCID= en-aut-name=WatanabeToyohiko en-aut-sei=Watanabe en-aut-mei=Toyohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= affil-num=1 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Holmium laser enucleation of the prostate kn-keyword=Holmium laser enucleation of the prostate en-keyword=Membranous urethral length kn-keyword=Membranous urethral length en-keyword=Magnetic resonance imaging kn-keyword=Magnetic resonance imaging en-keyword=Stress urinary incontinence kn-keyword=Stress urinary incontinence en-keyword=Quality of life kn-keyword=Quality of life en-keyword=Benign prostatic hyperplasia kn-keyword=Benign prostatic hyperplasia END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=8 article-no= start-page=494 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260807 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oral Supplementation of Bacillus subtilis Attenuated Alveolar Bone Loss in a Mouse Model of Ligature-Induced Periodontitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: This study aimed to investigate the effects of oral Bacillus subtilis (BS) on alveolar bone loss, intestinal morphology, and gut microbiota in a mouse model of ligature-induced periodontitis. Methods: A total of 24 male C57BL/6J mice (6 weeks old) were allocated to control, periodontitis (P), BS, and BS+P groups. Periodontitis was induced by bilateral ligation of maxillary second molars, and BS was orally administered for 18 consecutive days. Gut microbiota composition was analyzed by 16S rDNA sequencing, alveolar bone loss and gut morphology were evaluated using ImageJ version 1.54g, and ELISA-detectable serum vitamin D metabolite concentrations were measured using an enzyme-linked immunosorbent assay. Results: Compared with the P group, the BS+P group showed reduced bone loss. Serum vitamin D metabolite concentrations, small-intestine villus height, and villus height-to-crypt depth ratios were higher in the BS+P group. In gut microbiota, alpha diversity differed significantly among groups based on the Shannon index. Bray?Curtis-based beta diversity differed significantly among groups. Conclusions: Oral supplementation of BS attenuated the progression of ligature-induced periodontitis in a mouse model, and changes in gut microbiota may be associated with this effect. en-copyright= kn-copyright= en-aut-name=ZhangYixuan en-aut-sei=Zhang en-aut-mei=Yixuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ToyamaNaoki en-aut-sei=Toyama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NurhamimMohammad en-aut-sei=Nurhamim en-aut-mei=Mohammad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakaharaMomoko en-aut-sei=Nakahara en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukuharaDaiki en-aut-sei=Fukuhara en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaruyamaTakayuki en-aut-sei=Maruyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Dental School, Okayama University kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Dental School, Okayama University kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Bacillus subtilis kn-keyword=Bacillus subtilis en-keyword=periodontitis kn-keyword=periodontitis en-keyword=alveolar bone loss kn-keyword=alveolar bone loss en-keyword=gut microbiota kn-keyword=gut microbiota en-keyword=intestinal morphology kn-keyword=intestinal morphology en-keyword=vitamin D kn-keyword=vitamin D en-keyword=mouse model kn-keyword=mouse model END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue= article-no= start-page=102156 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=Pembrolizumab-based systemic therapy associated with opportunities for subsequent local treatment in advanced or recurrent neuroendocrine carcinoma of the cervix: a five-case series en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Neuroendocrine carcinoma (NEC) of the cervix is a rare, highly aggressive malignancy with limited evidence supporting immune checkpoint blockade. We evaluated the clinical activity of pembrolizumab-based therapy in patients with advanced or recurrent cervical NEC.
Methods: We retrospectively reviewed five consecutive patients with advanced or recurrent cervical NEC treated with pembrolizumab-based therapy at Okayama University Hospital between November 2022 and April 2025. Clinical characteristics, radiologic responses, molecular profiles, adverse events, local treatments, and survival outcomes were analyzed.
Results: The median age was 52 years. Three patients had newly diagnosed stage IVB disease, and two had recurrent metastatic disease after radical surgery and postoperative irinotecan plus cisplatin chemotherapy. All patients received paclitaxel plus carboplatin with pembrolizumab. An objective response was observed in all patients, including one complete response and four partial responses according to RECIST version 1.1. The median maximum tumor shrinkage was 78.5%, and median progression-free survival was 10.0 months. Comprehensive genomic profiling in four patients showed microsatellite-stable tumors with low tumor mutational burden in all evaluated cases. HPV association was supported by HPV16/18 sequences in three patients and diffuse p16 expression in one additional patient. Immune-related adverse events were grade 2 or lower. In three patients, systemic disease control allowed subsequent local treatment, including radiotherapy, conversion surgery, and stereotactic radiotherapy.
Conclusion: Pembrolizumab-based therapy showed encouraging clinical activity despite microsatellite-stable status and low tumor mutational burden in evaluated cases. Sustained systemic disease control may provide an opportunity for multimodal treatment incorporating subsequent local treatment. en-copyright= kn-copyright= en-aut-name=IdaNaoyuki en-aut-sei=Ida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaYui en-aut-sei=Tanaka en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujikawaAtsushi en-aut-sei=Fujikawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaniokaMomoko en-aut-sei=Tanioka en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ImataniRyoko en-aut-sei=Imatani en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TaniYoshinori en-aut-sei=Tani en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiharaHanako en-aut-sei=Sugihara en-aut-mei=Hanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuokaHirofumi en-aut-sei=Matsuoka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkamotoKazuhiro en-aut-sei=Okamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HaragaJunko en-aut-sei=Haraga en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Neuroendocrine carcinoma (NEC) kn-keyword=Neuroendocrine carcinoma (NEC) en-keyword=Cervical cancer kn-keyword=Cervical cancer en-keyword=Pembrolizumab kn-keyword=Pembrolizumab en-keyword=Immunotherapy kn-keyword=Immunotherapy en-keyword=Local intervention kn-keyword=Local intervention en-keyword=Case series kn-keyword=Case series END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=7 article-no= start-page=e72982 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=A Biologically Dominant Trophoblastic Component Guiding Neoadjuvant EMA/CO in Endometrial Carcinoma: A Clinical Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Endometrial carcinoma with choriocarcinomatous components (ECCC) is a rare and aggressive malignancy for which optimal management remains undefined. We report a case illustrating how preoperative identification of a biologically dominant trophoblastic component can guide treatment sequencing and achieve durable remission. A 61-year-old postmenopausal woman presented with abnormal uterine bleeding. Endometrial biopsy revealed a mixed tumor composed predominantly of choriocarcinomatous elements with a minor grade 1 endometrioid carcinoma component. Despite only superficial myometrial invasion, imaging demonstrated multiple pulmonary nodules, and serum human chorionic gonadotropin (hCG) was markedly elevated (46,538?mIU/mL). This clinicopathological incongruity suggested that the trophoblastic component, rather than the low-grade endometrioid carcinoma, was driving disease progression. Neoadjuvant EMA/CO chemotherapy was therefore prioritized to achieve rapid systemic control. After six cycles, serum hCG normalized and pulmonary lesions completely resolved. The patient subsequently underwent total hysterectomy and bilateral salpingo-oophorectomy, which revealed no residual choriocarcinoma. She remains disease-free more than two years after completion of treatment. This case highlights the importance of recognizing clinicopathological incongruity and identifying the biologically dominant tumor component when determining treatment sequencing in rare mixed malignancies. en-copyright= kn-copyright= en-aut-name=ShirakawaShinsuke en-aut-sei=Shirakawa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaYui en-aut-sei=Tanaka en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujikawaAtsushi en-aut-sei=Fujikawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImataniRyoko en-aut-sei=Imatani en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TaniokaMomoko en-aut-sei=Tanioka en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TaniYoshinori en-aut-sei=Tani en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiharaHanako en-aut-sei=Sugihara en-aut-mei=Hanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkamotoKazuhiro en-aut-sei=Okamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IdaNaoyuki en-aut-sei=Ida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsuokaHirofumi en-aut-sei=Matsuoka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HaragaJunko en-aut-sei=Haraga en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OgawaChikako en-aut-sei=Ogawa en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Diagnostic Pathology, Okayama University kn-affil= affil-num=16 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=choriocarcinoma kn-keyword=choriocarcinoma en-keyword=EMA/CO kn-keyword=EMA/CO en-keyword=endometrial cancer kn-keyword=endometrial cancer en-keyword=endometrioid carcinoma kn-keyword=endometrioid carcinoma END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=1 article-no= start-page=e0340963 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260113 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fertility-sparing surgery with neoadjuvant chemotherapy in early and locally advanced cervical cancer: A clinical protocol en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fertility preservation remains a critical concern in young women with early or locally advanced cervical cancer, as standard radical treatments compromise reproductive potential. This study aims to evaluate the feasibility, oncological safety, and reproductive outcomes of fertility-sparing treatment involving neoadjuvant chemotherapy followed by cervical conization and laparoscopic pelvic lymphadenectomy. This single-center, prospective, open-label, single-arm, Phase II interventional study will assess patients with FIGO stage IB2?IB3 cervical cancer (FIGO stage 2018) desiring fertility preservation. Eligible patients will receive three cycles of dose-dense paclitaxel and carboplatin (dd-TC), followed by conization and laparoscopic lymphadenectomy. The primary endpoint is successful uterine preservation. Patients requiring concurrent chemoradiotherapy due to inadequate treatment response will not be considered successful. Secondary endpoints include 2-year recurrence-free survival (RFS), overall survival (OS), quality of life assessments, menstrual and ovulatory resumption, pregnancy, live birth, miscarriage, and preterm birth. Adverse events will be graded according to CTCAE v5.0. en-copyright= kn-copyright= en-aut-name=TaniokaMomoko en-aut-sei=Tanioka en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IdaNaoyuki en-aut-sei=Ida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaYui en-aut-sei=Tanaka en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujikawaAtsushi en-aut-sei=Fujikawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ImataniRyoko en-aut-sei=Imatani en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TaniYoshinori en-aut-sei=Tani en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiharaHanako en-aut-sei=Sugihara en-aut-mei=Hanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkamotoKazuhiro en-aut-sei=Okamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuokaHirofumi en-aut-sei=Matsuoka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HaragaJunko en-aut-sei=Haraga en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OgawaChikako en-aut-sei=Ogawa en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=8 article-no= start-page=e0356180 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Study protocol: Effect of inulin supplementation on gut microbiota in patients with oral lichen planus ? A double-blind, randomised, placebo-controlled parallel-group trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oral lichen planus is a chronic inflammatory disease of the oral mucosa characterised by immune dysregulation, but its pathogenesis remains incompletely understood and no curative treatment has been established. Our previous work showed that patients with oral lichen planus exhibit gut dysbiosis, including reduced microbial diversity and depletion of butyrate-producing bacteria. Because butyrate promotes regulatory T-cell differentiation and supports immune homeostasis, targeting this dysbiosis may represent a microbiota-directed approach for immune modulation in oral lichen planus. This study aims to investigate the effects of inulin supplementation on the gut microbiota and related immune markers in patients with oral lichen planus. This multicentre, double-blind, randomised, placebo-controlled parallel-group trial will enrol 80 patients with oral lichen planus. Participants will be randomly assigned in a 1:1 ratio to receive either inulin (8 g/day) or a maltose placebo for 4 weeks, in addition to standard care. The primary outcome is the change in the relative abundance of prespecified butyrate-producing gut bacteria from baseline to the end of intervention at Week 6. Secondary outcomes include changes in gut microbiota diversity, salivary microbiota composition, faecal short-chain fatty acid concentrations, peripheral blood regulatory T-cell counts, blood test parameters, and clinical symptoms of oral lichen planus. Analyses will follow the intention-to-treat principle, and between-group differences will be assessed using appropriate statistical methods. This trial is designed to evaluate, in a randomised placebo-controlled setting, whether a microbiota-directed intervention can modify gut microbial profiles and related immune markers in patients with oral lichen planus. The findings are expected to clarify whether inulin supplementation can modify gut microbial profiles and related immunological markers in patients with oral lichen planus. Trial registration: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000060840, registered on 1 April 2026 (https://rctportal.mhlw.go.jp/detail/um?trial_id=UMIN000060840#). en-copyright= kn-copyright= en-aut-name=NambuKoki en-aut-sei=Nambu en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanekoNaoki en-aut-sei=Kaneko en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokomizoShiho en-aut-sei=Yokomizo en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChenHu en-aut-sei=Chen en-aut-mei=Hu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanLijing en-aut-sei=Yan en-aut-mei=Lijing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShiyaoWang en-aut-sei=Shiyao en-aut-mei=Wang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShizumaRyusei en-aut-sei=Shizuma en-aut-mei=Ryusei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwataEiji en-aut-sei=Iwata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhyamaYukiko en-aut-sei=Ohyama en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkagawaShohei en-aut-sei=Akagawa en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawanoShintaro en-aut-sei=Kawano en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MoriyamaMasafumi en-aut-sei=Moriyama en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=2 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=3 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=4 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=5 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=6 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=7 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=10 en-affil=Department of Pediatrics, Kansai Medical University kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=13 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=1 article-no= start-page=1039 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=Diversity of hymenopteran assemblages prevailed during reproductive stage of cotton?implications for natural control en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hymenoptera is one of the most important insect orders contributes to pollination, biocontrol and natural control largely unexplored from Bangladesh. We, therefore, assess the diversity and relative abundance of hymenopteran insects in cotton fields from five locations of Bangladesh using five types of traps (Malaise, Yellow Pan, Fluorescent Yellow Pan, Pitfall, and Sweep Net). Analysis of samples revealed presence of diverse type of hymenopteran insects from the studied locations, with a total of 1642 insects collected, representing 28 morphospecies and 16 families of the Hymenoptera. Formicidae, Braconidae, Diapridae, Figitidae, Ichneumonidae, Scelionidae constitutes the major families comprises of 36.37, 25.09, 5.36, 5.24, 5.18 and 4.93% of the populations respectively. Among the locations, cotton fields of Rangpur showed the highest species richness, diversity indices (Simpson, and Shannon values), while cotton fields located at Jashore had the lowest. Yellow and fluorescent pan traps captured insects from nearly all families, indicating broad sampling effectiveness. Malaise traps also sampled a wide range of families except for low captures of Formicidae. Pitfall traps primarily targeted Formicidae, consistent with their ground-dwelling hymenopterans. Sweep nets captured fewer families, reflecting a more selective sampling role. Among functional guilds, parasitoids were the most abundant, followed by predators, pollinators, and herbivores of hymenopteran insects. Overall, the hymenopteran community in cotton agroecosystems from Bangladesh was dominated by parasitoid families, indicating strong potential for natural biological control. Leveraging this natural enemy dominance could significantly reduce dependence on chemical insecticides. These findings support the integration of parasitoid conservation strategies into national Integrated Pest Management (IPM) programs and landscape-level pest management policies. en-copyright= kn-copyright= en-aut-name=RahmanMd Mizanur en-aut-sei=Rahman en-aut-mei=Md Mizanur kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayakawaTohru en-aut-sei=Hayakawa en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HowladerMohammad Tofazzal Hossain en-aut-sei=Howlader en-aut-mei=Mohammad Tofazzal Hossain kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Insect Biotechnology and Biopesticide Laboratory, Department of Entomology, Bangladesh Agricultural 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=Insect Biotechnology and Biopesticide Laboratory, Department of Entomology, Bangladesh Agricultural University kn-affil= en-keyword=Biodiversity kn-keyword=Biodiversity en-keyword=Hymenoptera kn-keyword=Hymenoptera en-keyword=Bangladesh kn-keyword=Bangladesh en-keyword=Baseline kn-keyword=Baseline en-keyword=Conservation kn-keyword=Conservation END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue=4 article-no= start-page=538 end-page=549 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=Enhancement of antioxidant function in various organs in mice using combined thermal and radon inhalation treatment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Enhancing antioxidant function is a key strategy for preventing and treating oxidative stress-related diseases. Radon inhalation and thermal treatment (TT) increase the levels of antioxidant enzymes, such as superoxide dismutase (SOD). The positive effects of this combination on pain-related diseases have been reported; however, few studies have elucidated the underlying mechanisms. In this study, we examined the enhancement of antioxidant function in various organs of mice subjected to combined TT and radon inhalation. The mice were placed in an incubator once daily for 40 min at 38.5 ± 0.5°C and treated for 1, 3 and 7 days. The mice then inhaled radon at a concentration of 2000 Bq/m3 for 24 h. The characteristic changes in antioxidant function following combined TT and radon inhalation could be categorized into four groups: (i) increased antioxidant function in the brain and colon; (ii) increased or decreased antioxidant function, as observed in the kidney; (iii) decreased antioxidant function, such as in the lungs and (iv) no changes, such as in the small intestine, spleen, pancreas, heart, liver and stomach. Additionally, SOD may be the antioxidant enzyme most sensitive to combined TT and radon treatment. Collectively, the combined treatment may be the most effective in activating antioxidative functions in the brain and colon. This study provides new insights into the effects of combined TT and radon inhalation. en-copyright= kn-copyright= en-aut-name=MiyanagaShogo en-aut-sei=Miyanaga en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaAyumi en-aut-sei=Tanaka en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakenakaReiju en-aut-sei=Takenaka en-aut-mei=Reiju kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaoeShota en-aut-sei=Naoe en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotoShuna en-aut-sei=Goto en-aut-mei=Shuna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NaganoMitsuki en-aut-sei=Nagano en-aut-mei=Mitsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanoKotaro en-aut-sei=Tano en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanzakiNorie en-aut-sei=Kanzaki en-aut-mei=Norie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakodaAkihiro en-aut-sei=Sakoda en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamaokaKiyonori en-aut-sei=Yamaoka en-aut-mei=Kiyonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KataokaTakahiro en-aut-sei=Kataoka en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency kn-affil= affil-num=5 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency kn-affil= affil-num=9 en-affil=Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency kn-affil= affil-num=10 en-affil=Faculty of Health Sciences, Okayama University kn-affil= affil-num=11 en-affil=Faculty of Health Sciences, Okayama University kn-affil= en-keyword=radon kn-keyword=radon en-keyword=thermal treatment kn-keyword=thermal treatment en-keyword=antioxidant function kn-keyword=antioxidant function en-keyword=oxidative stress kn-keyword=oxidative stress END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=e77709 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association Between Dinner-to-Bed Time and Gastroesophageal Reflux-Related Diseases in Children en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Gastroesophageal reflux disease (GERD) is characterized by esophageal mucosal injury due to the reflux of gastroduodenal contents. Typical symptoms include heartburn and acid regurgitation. In addition, gastroesophageal reflux (GER) can influence conditions such as otitis media, rhinitis, and asthma. This study aimed to examine the association between dinner-to-bed time and GER-related diseases, such as otitis media, allergic rhinitis, and asthma.
Methods: This was a longitudinal cohort study using secondary data. Data were collected from a large-scale birth cohort study conducted in Japan including babies born in 2001 and 2010. Dinner-to-bed time was categorized as “longer dinner-to-bed time" (>120 minutes), “shorter dinner-to-bed time" (?120 minutes or less), and “irregular dinner-to-bed time.” Modified Poisson regression with robust variance was used to estimate risk ratios (RRs).
Results: A total of 60,392 children were included in this study. Children with shorter dinner-to-bed time had a higher risk of asthma (adjusted RR (aRR)?=?1.10; 95% confidence interval (CI), 1.03-1.18) than those with longer dinner-to-bed time. However, no significant association was observed between shorter dinner-to-bed time and otitis media or allergic rhinitis. Furthermore, supplementary analyses revealed that the risk of asthma was significantly higher in children born in 2001 (aRR?=?1.13; 95% CI, 1.04-1.22).
Conclusion: This study showed that dinner-to-bed time within 120 minutes after dinner increases the risk of developing asthma. This underscores the importance of considering lifestyle modifications, as certain pediatric asthma cases may be influenced by behaviors that promote GER. en-copyright= kn-copyright= en-aut-name=UraguchiKensuke en-aut-sei=Uraguchi en-aut-mei=Kensuke 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=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=TakaoSoshi en-aut-sei=Takao en-aut-mei=Soshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MakiharaSeiichiro en-aut-sei=Makihara en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital 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 Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Otolaryngology- Head and Neck Surgery, 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=acute otitis media kn-keyword=acute otitis media en-keyword=allergic rhinitis (ar) kn-keyword=allergic rhinitis (ar) en-keyword=gastroesophageal reflux symptoms kn-keyword=gastroesophageal reflux symptoms en-keyword=pediatric asthma kn-keyword=pediatric asthma en-keyword=public health kn-keyword=public health END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=3 article-no= start-page=e80184 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cholecystectomy Is Linked to Worse Clinical Outcomes in Primary Sclerosing Cholangitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent findings have suggested that gallbladder-derived retinoic acid signaling plays a crucial role in the regeneration of damaged intrahepatic biliary ducts. This retrospective cohort study analyzed the clinical records of 20 patients with primary sclerosing cholangitis (PSC) treated at our hospital between 2013 and 2024. We investigated the clinical implications of gallbladder removal in patients with PSC, a progressive cholangiopathy with limited therapeutic options. We retrospectively analyzed the data of patients with PSC and compared patients with and without prior cholecystectomy to assess the impact on disease progression using the Mayo risk score, Fibrosis-4 (FIB4) index, and other clinical parameters. Our findings indicated that cholecystectomy was associated with worse Mayo risk scores (p = 0.0004) and an elevated FIB4 index (p = 0.021), suggesting a potential link between gallbladder removal and accelerated disease progression. Furthermore, mortality and transplant-free survival analysis revealed significantly worse outcomes in the cholecystectomy group (odds ratio = 21.0, p = 0.032). However, given the retrospective nature and small sample size of this study, selection bias cannot be excluded, and further research is needed to confirm these findings. These findings support the hypothesis that gallbladder-derived factors, such as retinoic acid, may influence PSC progression and highlight the need for further research into therapeutic interventions targeting this pathway. en-copyright= kn-copyright= en-aut-name=MiyakeNozomi en-aut-sei=Miyake en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YasugiKengo en-aut-sei=Yasugi en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=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 kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University 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 kn-affil= en-keyword=biliary diseases kn-keyword=biliary diseases en-keyword=cholecystectomy kn-keyword=cholecystectomy en-keyword=gall bladder kn-keyword=gall bladder en-keyword=liver function kn-keyword=liver function en-keyword=post cholecystectomy kn-keyword=post cholecystectomy en-keyword=primary sclerosing cholangitis (psc) kn-keyword=primary sclerosing cholangitis (psc) END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=2 article-no= start-page=e78399 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Rare Course of Chiari Malformation With Large Syringomyelia Presenting at 54 Years Old en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chiari malformation type 1 (CM1) is considered a congenital condition. The symptoms include severe headache, hypalgesia, and loss of temperature sensation. It constitutes a significant burden among children and young adults. The onset of symptoms of CM1 is more commonly observed in relatively young children and is very rare in those over 50 years old. This study aims to present a rare surgical case of CM1 associated with a large syringomyelia in a 54-year-old man.
A 54-year-old man with low back pain was introduced to our department. He had slight hyperreflexia of the extremities, slight muscle weakness in both legs, and numbness in the right leg (3/10). He also had urinary and bowel incontinence and spastic gait. Cervical magnetic resonance imaging (MRI) showed CM1 with large syringomyelia extending from C1 to T11. The cervical canal was widened because of a long history of spinal cord expansion.
The patient was successfully treated surgically by foramen magnum decompression and syringosubarachnoid shunting under the guidance of O-arm navigation. The muscle weakness and sensory function recovered almost entirely on the one-year follow-up. The patient's cervical Japanese Orthopedic Association (JOA) score had improved from 11/17 to 16/17.
Gradually enlarging syringomyelia with slight CM1 is rare, but surgeons should consider this condition's possibility. Foramen magnum decompression achieves good results even in cases with a long history of syringomyelia. This new navigation technique provides an excellent result for a large syringomyelia with CM1. en-copyright= kn-copyright= en-aut-name=TanakaMasato en-aut-sei=Tanaka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SharmaSneha en-aut-sei=Sharma en-aut-mei=Sneha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GoriKushal H en-aut-sei=Gori en-aut-mei=Kushal H kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShohidullahMd en-aut-sei=Shohidullah en-aut-mei=Md kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= affil-num=1 en-affil=Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Orthopedics, North Delhi Municipal Corporation (DMC) Medical College kn-affil= affil-num=3 en-affil=Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=4 en-affil=Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=5 en-affil=Orthopedic Surgery, Okayama University Hospital kn-affil= en-keyword=chiari malformation kn-keyword=chiari malformation en-keyword=foramen magnum decompression kn-keyword=foramen magnum decompression en-keyword=large syringomyelia kn-keyword=large syringomyelia en-keyword=navigation system kn-keyword=navigation system en-keyword=syringosubarachnoid shunting kn-keyword=syringosubarachnoid shunting 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=20260801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cathodic AziridinationUsing Dichloramine-Tas a Nitrogen Source en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aziridines are valuable motifs in organic synthesis due to their biological activities and their utility as synthetic intermediates. Although electrochemical methods have been developed for aziridine synthesis, these approaches rely on anodic oxidation. This study reports the first cathodic reduction-promoted aziridine formation using dichloramine-T as a nitrogen source. The reaction conditions were optimized via Gaussian process regression. Overall, this strategy enables aziridine formation with broad substrate scope, providing a practical platform that expands the electrochemical synthesis toolbox. en-copyright= kn-copyright= en-aut-name=SatoEisuke en-aut-sei=Sato en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagamineKanon en-aut-sei=Nagamine en-aut-mei=Kanon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsudoKoichi en-aut-sei=Mitsudo en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SugaSeiji en-aut-sei=Suga en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=10 article-no= start-page=e71325 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vonoprazan-Associated Mucosal Redness: A Report of Two Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vonoprazan, a potassium-competitive acid blocker, is effective at treating acid-related gastrointestinal disorders but has been linked to gastric mucosal redness, a novel condition. This report describes two cases of vonoprazan-associated mucosal redness. Case 1 involved a 73-year-old woman who developed longitudinal erythema and mild mucosal changes after starting vonoprazan seven years ago. Case 2 involved a 70-year-old man who exhibited significant erythema and atrophic gastritis after seven months of treatment. In both cases, the pathological findings included hemorrhage in the superficial mucosa, highlighting that microhemorrhage may be the corresponding pathological finding for vonoprazan-associated mucosal redness. 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=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu 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=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkedaNobumasa en-aut-sei=Ikeda en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Pathology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Internal Medicine, Clinic Ikeda kn-affil= en-keyword=endoscopy kn-keyword=endoscopy en-keyword=gastric mucosal redness kn-keyword=gastric mucosal redness en-keyword=microhemorrhage kn-keyword=microhemorrhage en-keyword=potassium-competitive acid blocker kn-keyword=potassium-competitive acid blocker en-keyword=vonoprazan kn-keyword=vonoprazan END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=3 article-no= start-page=e81104 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Pemafibrate and Eicosapentaenoic Acid Ethyl Ester on Endothelial Function in Patients With Hypertriglyceridemia and Coronary Artery Disease: A Study Protocol for a Multicenter, Open-Label Randomised Controlled Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Despite intensive low-density lipoprotein cholesterol-lowering therapies effectively reducing cardiovascular events, residual cardiovascular risks remain significant, with hypertriglyceridemia being an important contributing factor. Pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, has shown strong triglyceride-lowering effects and potential vascular benefits. Similarly, eicosapentaenoic acid ethyl ester (EPA) has demonstrated cardiovascular protective effects, particularly in patients with hypertriglyceridemia. However, the comparative impact of these agents on endothelial function, a key marker of atherosclerotic progression, has not been thoroughly evaluated in patients with coronary artery disease (CAD). The PRIME (PRospective comparIson of peMafibrate and Eicosapentaenoic acid ethyl ester on vascular functions for hypertriglyceridemia) trial is a multi-center, open-label, randomised trial designed to compare the effects of pemafibrate and EPA on endothelial function in patients with CAD and hypertriglyceridemia. Patients receiving statin therapy with fasting triglyceride levels ?150 mg/dL will be randomised into two groups: pemafibrate (0.2 mg/day, with possible dose escalation to 0.4 mg/day) or EPA (1800 mg/day, with possible dose escalation to 2700 mg/day). Endothelial function will be assessed with reactive hyperemia index (RHI). The primary endpoint is the change in RHI at 12 weeks. The secondary endpoints include the changes in RHI at 24 weeks, correlations between changes in RHI and changes in lipid biomarkers, and changes in biochemical parameters at 12 and 24 weeks. This study investigates the comparative effects of pemafibrate and EPA on endothelial function, addressing an unmet need in managing residual cardiovascular risk in patients with CAD. The findings will contribute to the optimisation of treatment strategies in patients with CAD and hypertriglyceridemia. en-copyright= kn-copyright= en-aut-name=MiyoshiTrou en-aut-sei=Miyoshi en-aut-mei=Trou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuzawaYasushi en-aut-sei=Matsuzawa en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DoiMasayuki en-aut-sei=Doi en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=SugiyamaSeigo en-aut-sei=Sugiyama en-aut-mei=Seigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Cardiovascular Medicine, Okayama University kn-affil= affil-num=2 en-affil=Cardiovascular Medicine, Kumamoto University kn-affil= affil-num=3 en-affil=Cardiology, Kagawa Prefectural Central Hospital kn-affil= affil-num=4 en-affil=Cardiovascular Medicine, Okayama University kn-affil= affil-num=5 en-affil=Cardiovascular Medicine, Jinnouchi Hospital kn-affil= en-keyword=cardiovascular risk kn-keyword=cardiovascular risk en-keyword=eicosapentaenoic acid kn-keyword=eicosapentaenoic acid en-keyword=endothelial function kn-keyword=endothelial function en-keyword=pemafibrate kn-keyword=pemafibrate en-keyword=triglyceride kn-keyword=triglyceride END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=8 article-no= start-page=e73170 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=Black Hairy Tongue in a 54‐Day‐Old Infant: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Black hairy tongue is a benign condition caused by elongation and defective desquamation of the filiform papillae, and it is uncommon in neonates and infants. We report a case in a 54-day-old girl who presented with a black lesion on the tongue dorsum. The lesion had first been noted at the 1-month medical checkup and persisted despite observation. At presentation, a localized blackish-brown lesion with accentuated filiform papillae was observed on the tongue dorsum and could not be wiped off with gauze. Oral candidiasis was considered in the differential diagnosis, but microbiological examination detected no Candida species. A clinical diagnosis of black hairy tongue was made, and the parents were instructed to gently clean the tongue dorsum with gauze and a sponge brush. The lesion resolved within 2?weeks without recurrence. Recognition of this benign entity may help avoid unnecessary treatment in infants. en-copyright= kn-copyright= en-aut-name=MasuiMasanori en-aut-sei=Masui en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakamotoYumi en-aut-sei=Sakamoto en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=black hairy tongue kn-keyword=black hairy tongue en-keyword=case report kn-keyword=case report en-keyword=infant kn-keyword=infant en-keyword=oral hygiene kn-keyword=oral hygiene END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=1 article-no= start-page=88 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260731 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Early-Stage Oral Squamous Cell Carcinoma in Adolescents and Young Adults Compared with Older Patients Exhibits Distinct Clinicopathological Features en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose This study aimed to compare the clinicopathological features of stage I?II oral squamous cell carcinoma (OSCC) between adolescents and young adults (AYAs) and older patients, and to identify prognostic factors in AYA OSCC.
Methods Forty-eight AYA patients aged 15?39 years and 69 older patients aged???65 years with surgically treated stage I?II OSCC were retrospectively analyzed. Histological evaluation, survival analysis, immunohistochemistry for p53, p16, and MTAP, high-risk HPV RNA in situ hybridization, and fluorescence in situ hybridization for CDKN2A and MTAP were performed.
Results Compared with older patients, OSCCs in AYAs were more frequently located on the tongue (93.7% vs. 47.8%) and more often exhibited a superficial spreading growth pattern (60.4% vs. 31.8%). AYA tumors more frequently showed modified WPOI-1, high tumor budding, and abnormal p53 immunophenotypes (85.4% vs. 68.1%). AYA patients showed significantly better overall and disease-free survival than older patients. Within the AYA group, depth of invasion (DOI)?>?5 mm was associated with distant metastasis and poorer overall and disease-free survival. Postoperative lymph node metastasis occurred in 31.2% of AYAs. Univariable analysis suggested that clinical stage II, tumor thickness?>?5 mm, DOI?>?5 mm, and tumor budding scores 1?2 were associated with postoperative lymph node metastasis. Molecular status, including p53, p16/CDKN2A, and MTAP, did not provide robust prognostic stratification.
Conclusion Early-stage AYA OSCC exhibits distinct clinicopathological features. DOI was the strongest prognostic indicator, whereas clinical stage, tumor thickness, and tumor budding may provide additional prognostic information regarding the risk of late nodal metastasis. en-copyright= kn-copyright= en-aut-name=OnoSawako en-aut-sei=Ono en-aut-mei=Sawako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiroseKatsutoshi en-aut-sei=Hirose en-aut-mei=Katsutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeTatsuya en-aut-sei=Abe en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MasuiMasanori en-aut-sei=Masui en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkedaChihoko en-aut-sei=Ikeda en-aut-mei=Chihoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IsomuraMadoka en-aut-sei=Isomura en-aut-mei=Madoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TachibanaYuri en-aut-sei=Tachibana en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OnoJunya en-aut-sei=Ono en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShimadaKatsumitsu en-aut-sei=Shimada en-aut-mei=Katsumitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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 Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Pathology, Osaka University Graduate School of Dentistry kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology, Osaka Dental University kn-affil= affil-num=8 en-affil=Department of Diagnostic Pathology, School of Medicine, Fujita Health University kn-affil= affil-num=9 en-affil=Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Faculty of Medicine kn-affil= affil-num=10 en-affil=Department of Pathology, The Nippon Dental University School of Life Dentistry at Niigata kn-affil= affil-num=11 en-affil=Department of Clinical Pathophysiology, School of Dentistry, Matsumoto Dental University kn-affil= affil-num=12 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Squamous cell carcinoma of head and neck kn-keyword=Squamous cell carcinoma of head and neck en-keyword=Mouth neoplasms kn-keyword=Mouth neoplasms en-keyword=Adolescent kn-keyword=Adolescent en-keyword=Young adult kn-keyword=Young adult en-keyword=Prognosis kn-keyword=Prognosis en-keyword=Immunohistochemistry kn-keyword=Immunohistochemistry en-keyword=Tumor suppressor protein p53 kn-keyword=Tumor suppressor protein p53 END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=12 article-no= start-page=1811 end-page=1822 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=ABA receptor isoforms differently regulate stomatal movements and generation of reactive oxygen species in ABA signaling in Arabidopsis guard cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=ABA signaling in stomatal guard cells is crucial for plants to cope with abiotic stress condition. Pyrabactin is a synthetic agonist of ABA that has a selective affinity to limited isoforms of ABA receptors. Here, we investigated the differential utilization of downstream signaling events in guard cell ABA signaling under specific receptor isoforms taking advantage of pyrabactin affinity. Pyrabactin-induced stomatal closure as well as ABA, while it did not inhibit stomatal opening. Plasma membrane inwardly rectifying K+ channel was not regulated by pyrabactin, while H+-ATPase activation was negatively regulated by pyrabactin. Pharmacological and molecular genetic evidence supported that reactive oxygen species production occurred differentially between the closure-inducing and opening-inhibiting signals in guard cells. These findings offer a previously unidentified mechanism for ABA signaling events promoting closure induction and opening inhibition of stomata, which were distinct from each other and governed by different ABA receptor isoforms discriminable by their affinity for pyrabactin. en-copyright= kn-copyright= en-aut-name=YinYe en-aut-sei=Yin en-aut-mei=Ye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayashiYuki en-aut-sei=Hayashi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SirajamMonira en-aut-sei=Sirajam en-aut-mei=Monira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShaiekOumayma en-aut-sei=Shaiek en-aut-mei=Oumayma 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=NakamuraYoshimasa en-aut-sei=Nakamura en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KinoshitaToshinori en-aut-sei=Kinoshita en-aut-mei=Toshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=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 Science, Nagoya 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 Science, Nagoya University kn-affil= affil-num=8 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=9 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e71464 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260729 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis of Tris(indol-3-yl)methanes From Indoles, CO2, and Dimethylphenylsilane With BPh3: Two-Step Construction of π-Conjugated Systems en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tris(indol-3-yl)methanes were synthesized from indoles, CO2, and PhMe2SiH in the presence of BPh3 in acetonitrile at 50°C. This is the first CO2 fixation reaction forming the aliphatic methine (>CH─) group. The isotope-labeling experiments clearly demonstrated that the carbon and hydrogen atoms of the methine group originated from carbon dioxide and dimethylphenylsilane, respectively. The mechanism for the multicomponent cascade reaction was elucidated by DFT calculations. One of the CO2-derived products, tris(4-bromo-1-methylindol-3-yl)methane, underwent palladium-catalyzed intramolecular cascade reactions for the selective formation of two novel polycyclic heteroaromatic compounds, where the methine C(sp3) atom originating from CO2 was converted into aromatic C(sp2) atoms. One is formally produced via double direct C─H arylation, Wacker-type oxidation, dehydrogenation, and debromination, while the other seems to be produced via the intramolecular homocoupling of aryl bromide, direct C─H arylation, Wacker-type oxidation, and dehydrogenation. Both of them are new intramolecular cascade reactions that are useful for the short-step construction of nitrogen-doped nanographenes. On the other hand, one of the CO2-derived products, tris(1-pentylindol-3-yl)methane, was converted into tris(1-pentylindol-3-yl)methylium methanesulfonate, which is a potential antitumor drug. This is the first derivatization of CO2 to a cationic C(sp2) center. en-copyright= kn-copyright= en-aut-name=LiSha en-aut-sei=Li en-aut-mei=Sha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaibaraSo en-aut-sei=Saibara en-aut-mei=So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuiReito en-aut-sei=Yasui en-aut-mei=Reito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakaishiKazuto en-aut-sei=Takaishi en-aut-mei=Kazuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NittaNatsumi en-aut-sei=Nitta en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EmaTadashi en-aut-sei=Ema en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=boranes kn-keyword=boranes en-keyword=carbondioxidefixation kn-keyword=carbondioxidefixation en-keyword=cascadereaction kn-keyword=cascadereaction en-keyword=heteroaromatics kn-keyword=heteroaromatics en-keyword=silanes kn-keyword=silanes END start-ver=1.4 cd-journal=joma no-vol=541 cd-vols= no-issue= article-no= start-page=113868 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=Development of a novel histidine-rich glycoprotein measurement system as a biomarker for sepsis en-subtitle= kn-subtitle= en-abstract= kn-abstract=The plasma histidine-rich glycoprotein concentration is a marker of sepsis severity. In this study, we generated selective and specific monoclonal antibodies against histidine-rich glycoprotein for use in a prototype enzyme-linked immunosorbent assay-based in vitro diagnostic system. First, we investigated the properties of monoclonal antibodies produced by 21 hybridomas that we developed using immunized mice, and we identified monoclonal antibodies 69-1A and 75-2D to be the most suitable combination for use in the sandwich enzyme-linked immunosorbent assay. Wild-type histidine-rich glycoprotein (Form-1, 75 kDa) with a proline residue at amino acid position 204 is the most common isoform of the protein in humans, followed by its variant (Form-2, 77 kDa), which has a serine residue at position 204.
The epitope mapping was examined for the HRG amino acid sequence with 69-1A and 75-2D mAbs to achieve the identification of respective specific binding domains, though the other kinds of mAbs showed considerably complex domains. The identified epitopes recognized by 69-1A and 75-2D monoclonal antibodies did not span position 204. Furthermore, immunoprecipitation-immunoblotting analysis showed that the 69-1A and 75-2D monoclonal antibodies could bind to both Form-1 and Form-2 in human plasma samples. Thus, these two new antibodies can be used to clearly detect both forms of histidine-rich glycoproteins in human plasma samples. In our analysis of clinical samples by enzyme-linked immunosorbent assays using various combinations of our newly synthesized antibodies, we found that the histidine-rich glycoprotein concentration was significantly lower in plasma samples from septic patients than in those from healthy volunteers (p < 0.01). Thus, our novel analysis system using the new antibodies is expected to be a useful tool for sepsis research, and it may be adapted as an in vitro diagnostic tool for many other kinds of diseases in the future. en-copyright= kn-copyright= en-aut-name=UchiumiTakaoki en-aut-sei=Uchiumi en-aut-mei=Takaoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueYoko en-aut-sei=Inoue en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiHiroshi en-aut-sei=Nishi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtaNorio en-aut-sei=Ota en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Diagnostic Drug Office, Shionogi & Co., Ltd. kn-affil= affil-num=2 en-affil=Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Diagnostic Drug Office, Shionogi & Co., Ltd. kn-affil= affil-num=5 en-affil=Diagnostic Drug Office, Shionogi & Co., Ltd. kn-affil= affil-num=6 en-affil=Diagnostic Drug Office, Shionogi & Co., Ltd. kn-affil= en-keyword=Histidine-rich glycoprotein kn-keyword=Histidine-rich glycoprotein en-keyword=Sandwich enzyme-linked immunosorbent assay kn-keyword=Sandwich enzyme-linked immunosorbent assay en-keyword=In vitro diagnostics kn-keyword=In vitro diagnostics en-keyword=Sepsis kn-keyword=Sepsis en-keyword=Anti-human histidine-rich glycoprotein mouse monoclonal antibody kn-keyword=Anti-human histidine-rich glycoprotein mouse monoclonal antibody END start-ver=1.4 cd-journal=joma no-vol=49 cd-vols= no-issue=7 article-no= start-page=1992 end-page=2003 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260514 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of population-approach programs promoting salt reduction and potassium intake in Japan: the Population-based Sodium/Potassium Improvement Program (PoSPIP) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Reducing sodium intake in populations is essential, but insufficient for preventing and managing high blood pressure, while the importance of increasing potassium intake is overlooked. We investigated the effects of 1-year population-approach programs (2021?2022) promoting salt reduction and potassium intake using urinalysis feedback and food environment improvement. This retrospective observational study included 7649 participants (mean age, 54.0 years; 45.3% women) from 11 municipalities and 4 workplaces. Outcomes in intensive support programs?including urinary sodium, potassium, and sodium-to-potassium (Na/K) ratio measurements with feedback, dietary promotion, and food environment improvement?were compared with standard support programs providing usual health guidance. In linear regression adjusted for demographics, lifestyle factors, and medical history, the reduction in urinary Na/K ratio was greater in the intensive support group (n?=?4064) than in the standard support group (n?=?3585) (mean difference ?0.14 [95% confidence interval, ?0.27 to ?0.01]). Although estimated potassium intake decreased in both groups, the decline was smaller in the intensive support group (mean difference 31 [12 to 51] mg/day). Estimated salt intake did not differ between the groups. The intensive support group showed greater increases in diastolic blood pressure and high-density lipoprotein cholesterol and smaller increases in blood glucose, as well as greater reductions in hemoglobin A1c and Salt Check Sheet scores. Mean differences between the groups for endpoints were not heterogeneous across intensive support program types. Our findings support the development of hypertension prevention and management strategies that promote healthier dietary behaviors and can be implemented in community and workplace settings, with broad public health applicability. en-copyright= kn-copyright= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KinutaMinako en-aut-sei=Kinuta en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=TsuchihashiTakuya en-aut-sei=Tsuchihashi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshitaKatsushi en-aut-sei=Yoshita en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakemiYukari en-aut-sei=Takemi en-aut-mei=Yukari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HayabuchiHitomi en-aut-sei=Hayabuchi en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamiYukiko en-aut-sei=Okami en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KitaokaKaori en-aut-sei=Kitaoka en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakaguchiKeiko en-aut-sei=Sakaguchi en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HozawaAtsushi en-aut-sei=Hozawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkamuraTomonori en-aut-sei=Okamura en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ItohHiroshi en-aut-sei=Itoh en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=RakugiHiromi en-aut-sei=Rakugi en-aut-mei=Hiromi 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=MiuraKatsuyuki en-aut-sei=Miura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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 Hygiene and Public Health, Teikyo University School of Medicine kn-affil= affil-num=4 en-affil=Cardiovascular Center, Steel Memorial Yawata Hospital kn-affil= affil-num=5 en-affil=Department of Public Health, Nutrition, School of Human Life and Ecology, Osaka Metropolitan University kn-affil= affil-num=6 en-affil=Faculty of Nutrition, Kagawa Nutrition University kn-affil= affil-num=7 en-affil=Graduate School of Health and Environmental Sciences, Fukuoka Women’s University kn-affil= affil-num=8 en-affil=Gunma University Center for Food Science and Wellness kn-affil= affil-num=9 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=10 en-affil=Faculty of Nursing and Nutrition, Shukutoku University kn-affil= affil-num=11 en-affil=Division of Epidemiology, School of Public Health, Tohoku University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Preventive Medicine and Public Health, Keio University School of Medicine kn-affil= affil-num=13 en-affil=Japanese Society of Hypertension kn-affil= affil-num=14 en-affil=Japanese Society of Hypertension kn-affil= affil-num=15 en-affil=Japanese Society of Hypertension kn-affil= affil-num=16 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= en-keyword=Implemental hypertension kn-keyword=Implemental hypertension en-keyword=Sodium kn-keyword=Sodium en-keyword=Potassium kn-keyword=Potassium en-keyword=Urinalysis kn-keyword=Urinalysis en-keyword=Food environment kn-keyword=Food environment END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=29 article-no= start-page=12214 end-page=12224 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=Terpolymerization of epoxide, oxetane, and CO2 for the synthesis of polycarbonates with high CO2 contents, physical tunability, and enzymatic degradability en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although poly(cyclohexene carbonate) (PCHC) synthesized by the copolymerization of cyclohexene oxide (CHO) and CO2 is a promising material, the physical properties of this material need to be altered and tuned for its wider applications. To this end, we employed a terpolymerization strategy increasing the CO2 content in the resulting polymers. Terpolymerization of CHO, oxetane, and CO2 using AlIII porphyrin catalysts with quaternary ammonium halides afforded polycarbonates with high CO2 contents, physical tunability, and enzymatic degradability. The counter anions of the catalysts were crucial factors in the formation of the poly(trimethylene carbonate) (PTMC) unit. 1a with bromide ions preferentially produced trimethylene carbonate (TMC) over PTMC, while 1d with chloride ions suppressed the formation of TMC and produced PCHC?PTMC directly. PCHC?PTMC showed glass transition temperatures (Tg) between 69 °C and ?9 °C, depending on the PCHC/PTMC ratio. The tensile test revealed that the PTMC unit contributed to the softening of the film materials. For example, a film material with a CO2 content of 38 wt% showed 505% elongation at break with an elastic character, which contrasted starkly with the 1.3% elongation at break of PCHC with a CO2 content of 31 wt%. Moreover, the selective degradation of the PTMC unit in PCHC?PTMC was achieved with lipases, and a gradient character in the sequence structure was suggested. Overall, PCHC?PTMC is an environmentally benign and sustainable CO2-based polycarbonate. en-copyright= kn-copyright= en-aut-name=NikiKaito en-aut-sei=Niki en-aut-mei=Kaito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaedaChihiro en-aut-sei=Maeda en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EmaTadashi en-aut-sei=Ema en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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= END start-ver=1.4 cd-journal=joma no-vol=53 cd-vols= no-issue=14 article-no= start-page=e2026GL122472 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Electrical Conductivity of Hydrous Ultramafic Melts With Implications for Origin of Low Velocity Layer Atop of the 410?km Seismic Discontinuity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Low-velocity layers (LVLs) above the 410-km discontinuity are commonly attributed to partial melt generated by dehydration melting when hydrous mantle transition-zone material rises into the upper mantle, where water solubility in nominally anhydrous minerals decreases. Interpreting coexisting high-conductivity anomalies requires constraints on the intrinsic conductivity of the melt phase at pressures just above the transition zone. We measured electrical conductivity of hydrous ultramafic melts representative of incipient melts, ranging from 6.3 to 18.6 wt% H2O at 13 GPa using impedance spectroscopy in a Kawai-type multi-anvil apparatus. Hydrous ultramafic melts are extremely conductive, and conductivity increases systematically with H2O content to values comparable to alkali-carbonate melts. The high conductivity implies that even small fractions of interconnected hydrous melt can dominate bulk mantle conductivity. Combining our measurements with geophysical conductance estimates indicates that <1 vol% melt can produce conductive layers thicker than 10 km, consistent with seismological constraints on LVL structure. en-copyright= kn-copyright= en-aut-name=YoshinoTakashi en-aut-sei=Yoshino en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=XieLongjian en-aut-sei=Xie en-aut-mei=Longjian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Center for High Pressure Science & Technology Advanced Research kn-affil= en-keyword=electrical conductivity kn-keyword=electrical conductivity en-keyword=water kn-keyword=water en-keyword=low velocity zone kn-keyword=low velocity zone en-keyword=silicate melt kn-keyword=silicate melt en-keyword=mantle kn-keyword=mantle END start-ver=1.4 cd-journal=joma no-vol=2026 cd-vols= no-issue=1 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=Carcinoma ex Pleomorphic Adenoma With an Epithelial‐Myoepithelial Carcinoma Component in the Submandibular Gland: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Carcinoma ex pleomorphic adenoma (CXPA) is an uncommon malignant salivary gland tumor arising from pleomorphic adenoma, whereas epithelial-myoepithelial carcinoma (EMC) is a rare low-grade salivary gland malignancy. CXPA with an EMC component in the submandibular gland is uncommon.
Case Report: A 65-year-old man presented with a painless, firm mass in the left submandibular region and weakness of the left lower lip. Computed tomography and magnetic resonance imaging demonstrated an irregular submandibular mass, and FDG-PET/CT showed increased uptake (maximum standardized uptake value, 9.2). Core biopsy suggested pleomorphic adenoma; however, the clinical and radiological findings strongly indicated malignancy. Incisional biopsy was therefore performed under general anesthesia, with a plan to proceed to definitive treatment if malignancy was confirmed. Intraoperative histopathological examination revealed a malignant salivary gland tumor, and tumor resection with neck dissection was completed during the same procedure. Histopathological examination showed invasive CXPA with an EMC component, accompanied by extracapsular invasion exceeding 6?mm, perineural invasion, and extension into adjacent muscle (pT3N0). Although surgical margins were negative, pulmonary metastases developed 12 months after surgery, followed by suspected pleural dissemination and spinal canal extension. The patient declined further aggressive treatment and died of the disease 48 months after surgery.
Conclusion: This case highlights the importance of integrating clinical, radiological, and pathological findings for accurate diagnosis of salivary gland tumors, particularly when biopsy results are inconsistent with clinical suspicion. en-copyright= kn-copyright= en-aut-name=YasuharaTomohiro en-aut-sei=Yasuhara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MasuiMasanori en-aut-sei=Masui en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakakuraHiroaki en-aut-sei=Takakura en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwataEiji en-aut-sei=Iwata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KadoyaKoichi en-aut-sei=Kadoya en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UmemoriKoki en-aut-sei=Umemori en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshiokaNorie en-aut-sei=Yoshioka en-aut-mei=Norie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=carcinoma ex pleomorphic adenoma kn-keyword=carcinoma ex pleomorphic adenoma en-keyword=case report kn-keyword=case report en-keyword=epithelial-myoepithelial carcinoma kn-keyword=epithelial-myoepithelial carcinoma en-keyword=salivary gland neoplasm kn-keyword=salivary gland neoplasm en-keyword=submandibular gland kn-keyword=submandibular gland 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=20260717 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tripartite Interaction Between Penicillium pinophilum-Host Plants and CMV-Y: A Model for Endophyte-Mediated Viral Biocontrol en-subtitle= kn-subtitle= en-abstract= kn-abstract=Plant-fungus-virus tripartite interactions represent complex ecological systems in which mutualistic endophytes can influence host physiology, yet the molecular basis of endophyte-mediated defence remains poorly understood. Here, we demonstrate that the endophytic fungus Penicillium pinophilum EU0013 suppresses the yellow strain of cucumber mosaic virus (CMV-Y) in Solanum lycopersicum and Nicotiana benthamiana. CMV-Y infection induced pronounced oxidative and hormonal perturbations, which were mitigated by P. pinophilum colonisation. Endophyte-associated plants exhibited early accumulation of jasmonate intermediates, consistent with the activation of jasmonate signalling. This response promoted the degradation of jasmonate-ZIM-domain proteins and release of core JA-responsive transcription factors. Virus-induced gene silencing identified MYC2 as a key regulator required for endophyte-mediated antiviral protection, with WRKY17 contributing to defence modulation. In parallel, transcriptome analysis revealed the upregulation of a Dicer-like gene, indicating enhanced engagement of RNA silencing, a primary antiviral mechanism targeting viral RNA. This coordinated activation occurred alongside significant induction of pathogenesis-related proteins, particularly PR9, and improved control of reactive oxygen species. Salicylic acid-responsive defences showed a host-modulated pattern, with PR1 induced by CMV and PR2/PR5 preferentially enhanced in endophyte-associated plants. Collectively, these findings demonstrate that P. pinophilum enhances antiviral immunity through coordinated defence integration pathways, providing a framework for endophyte-based viral disease management. en-copyright= kn-copyright= en-aut-name=IbiangSarah R. en-aut-sei=Ibiang en-aut-mei=Sarah R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GalisIvan en-aut-sei=Galis en-aut-mei=Ivan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Group of Plant-Microbe Interactions, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Group of Plant-Insect Interactions, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Group of Plant-Microbe Interactions, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Group of Plant-Microbe Interactions, Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=cucumber mosaic virus kn-keyword=cucumber mosaic virus en-keyword=endophyte‐mediated resistance kn-keyword=endophyte‐mediated resistance en-keyword=jasmonate signalling kn-keyword=jasmonate signalling en-keyword=pathogenesis‐related proteins kn-keyword=pathogenesis‐related proteins en-keyword=solanaceae kn-keyword=solanaceae en-keyword=tripartite interaction kn-keyword=tripartite interaction 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=20260722 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dissociation between globe shape-induced rectus muscle pulley displacement and abduction limitation in patients aged 40?years and older with high myopic strabismus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose We hypothesized that high myopia (HM)-induced globe deformation displaces rectus muscle (RM) pulleys, contributing to mild ocular motility restriction. This study investigated the effects of globe shape on RM pulley positions in older Japanese patients with acquired strabismus (AS) and mild motility restriction?defined as the ability to abduct both eyes beyond the midline.
Methods In this retrospective case series, 28 patients (mean age?±?standard deviation: 61.2?±?9.0 years) with adult-onset AS were included: 6 patients with (LAB group) and 22 patients without abduction limitation (NLAB group). In each subject, the eye with the longer axial length (AL???26 mm), measured using an AL measurement apparatus, was analyzed using magnetic resonance imaging (MRI). RM pulley positions relative to the globe center and equatorial diameter (ED) were measured; the ED-to-AL ratio (EAR) was calculated. We compared these parameters between groups and analyzed correlations of globe-shape factors (EAR, AL, and ED) with pulley positions and age.
Results No significant differences in EAR, AL, ED, or pulley positions were detected between LAB and NLAB groups, possibly owing to the limited sample size and group imbalance, in the analyzed eyes. However, as EAR decreased (prolate deformation), the superior rectus (SR) pulley (r?=?0.68, P? Conclusions In older Japanese patients with HM and AS, prolate globe deformation was associated with age and significantly correlated with SR and IR pulley positions. While the direct relationship between these structural changes and the clinical degree of mild abduction limitation requires further investigation in larger cohorts, EAR sensitively reflected age-related morphological shifts; thus, when used in conjunction with AL, EAR may represent a readily measurable MRI-based parameter associated with restrictive motility tendencies in strabismus with high myopia. en-copyright= kn-copyright= en-aut-name=KonoReika en-aut-sei=Kono en-aut-mei=Reika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamasakiIchiro en-aut-sei=Hamasaki en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KishimotoFumiko en-aut-sei=Kishimoto en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShibataKiyo en-aut-sei=Shibata en-aut-mei=Kiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MorisawaShin en-aut-sei=Morisawa en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=Lino Eye Clinic kn-affil= affil-num=3 en-affil=Division of Ophthalmology, Ibara City Hospital kn-affil= affil-num=4 en-affil=Lino Eye Clinic 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= en-keyword=Heavy eye syndrome kn-keyword=Heavy eye syndrome en-keyword=High myopia kn-keyword=High myopia en-keyword=Magnetic resonance imaging kn-keyword=Magnetic resonance imaging en-keyword=Prolate deformation kn-keyword=Prolate deformation en-keyword=Rectus muscle pulley kn-keyword=Rectus muscle pulley en-keyword=Strabismus kn-keyword=Strabismus END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=6 article-no= start-page=103486 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Students’ perceptions of an electronic one-minute paper in a radiography training programme: An exploratory cross-sectional questionnaire study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Formative assessment can support health professions education; however, reports on electronic 1-min papers as classroom feedback and engagement tools in radiography programmes remain limited. This study explored radiography students’ perceptions of an electronic 1-min paper, focusing on in-class reflection, ease of asking questions, and instructor feedback.
Methods: An electronic 1-min paper was used in a radiotherapy course across 45 class sessions in the 2024 academic year for third-year students enrolled in a 4-year radiography programme. Each 90-min class comprised a 60-min lecture, 10-min completion of the paper, and 20-min instructor feedback. After the course, a de-identified online questionnaire was administered. Eleven 5-point Likert-scale items were analysed using descriptive statistics and Spearman's rank correlations. Free-text responses were analysed using inductive qualitative content analysis.
Results: Of the 77 eligible students, 74 responded (96.1%). Ease of use received the highest rating (mean, 4.76; standard deviation [SD], 0.52), followed by ease of asking questions (mean, 4.32), question resolution (mean, 4.16), and usefulness of instructor feedback (mean, 4.08). Motivation to review after class was lowest (mean, 3.04; SD, 1.16). Active participation showed a strong positive association with in-class concentration (rs = 0.815; P < 0.001). Free-text responses indicated reflection and improved understanding, anonymous sharing of questions, active listening and concentration, and suggestions for improvement.
Conclusion: The electronic 1-min paper was widely accepted and perceived to support in-class reflection, question expression, and immediate feedback. However, students’ perceptions of its influence on out-of-class review motivation were limited. The findings indicate perceived value and engagement rather than demonstrated educational effectiveness.
Implications for practice: Electronic 1-min papers may help instructors identify students’ questions and respond during class, providing a practical approach to in-class feedback. en-copyright= kn-copyright= en-aut-name=KomatsuY. en-aut-sei=Komatsu en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AbeS. en-aut-sei=Abe en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsudouS. en-aut-sei=Tsudou en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoY. en-aut-sei=Yamamoto en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanabeY. en-aut-sei=Tanabe en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Faculty of Health Care Sciences, Jikei University of Health Care Sciences kn-affil= affil-num=3 en-affil=Department of Radiological Technology, Faculty of Health Care Sciences, Jikei University of Health Care Sciences kn-affil= affil-num=4 en-affil=Division of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Health Sciences, Department of Radiological Technology, Okayama University Medical School, Okayama University kn-affil= en-keyword=Electronic 1-min paper kn-keyword=Electronic 1-min paper en-keyword=Formative assessment kn-keyword=Formative assessment en-keyword=Radiography education kn-keyword=Radiography education en-keyword=Immediate feedback kn-keyword=Immediate feedback en-keyword=Student engagement kn-keyword=Student engagement en-keyword=Health professions education kn-keyword=Health professions education END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue= article-no= start-page=1875734 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Quantitative resistance to Rhizoctonia solani AG-4 develops independently in leaves and roots of Brachypodium distachyon en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rhizoctonia solani is a soil-borne phytopathogen with a broad host range, classified into multiple anastomosis groups (AGs). While the rice sheath blight pathogen AG-1 IA is well-studied, defense mechanisms against AG-4, which infects diverse monocots and dicots, remain unclear. Here, we screened 153 Brachypodium distachyon accessions for resistance to AG-4 HG-I+II using both leaf and soil inoculation assays. The accessions exhibited a quantitative resistance spectrum in both assays. Some accessions were resistant to both methods, while others showed resistance in only one, indicating that leaf and root defenses operate independently. Unlike the salicylic acid (SA)-dependent resistance observed in several accessions against AG-1 IA, AG-4 leaf resistance appears to be largely SA-independent. Among 22 resistant accessions, only eight induced the SA marker BdWRKY38, whereas twelve induced the jasmonic acid (JA) marker BdAOS. Additionally, resistance in Bd3?1 was unaffected by expression of the SA hydroxylase NahG. These results are consistent with previous findings that exogenous application of SA, JA, or ethylene fails to confer AG-4 resistance. Instead, most AG-4-resistant accessions showed common upregulation of cell wall biosynthesis-related genes following leaf infection, suggesting that cell wall fortification may contribute to defense against AG-4. These findings establish B. distachyon as a valuable model for dissecting resistance mechanisms against R. solani AG-4. en-copyright= kn-copyright= en-aut-name=FernandaRozi en-aut-sei=Fernanda en-aut-mei=Rozi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MahadevanNiranjan en-aut-sei=Mahadevan en-aut-mei=Niranjan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KohnoNatsuka en-aut-sei=Kohno en-aut-mei=Natsuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagaoReiko en-aut-sei=Nagao en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeMegumi en-aut-sei=Watanabe en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 ORCID= en-aut-name=KouzaiYusuke en-aut-sei=Kouzai en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MochidaKeiichi en-aut-sei=Mochida en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=School of Agriculture, Okayama University kn-affil= affil-num=4 en-affil=School of Agriculture, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Crop Stress Management Group, Division of Plant Molecular Regulation Research, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO) kn-affil= affil-num=11 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=12 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Brachypodium distachyon kn-keyword=Brachypodium distachyon en-keyword=cell wall fortification kn-keyword=cell wall fortification en-keyword=phytohormone kn-keyword=phytohormone en-keyword=quantitative resistance kn-keyword=quantitative resistance en-keyword=Rhizoctonia solani kn-keyword=Rhizoctonia solani en-keyword=root infection kn-keyword=root infection END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=1 article-no= start-page=109 end-page=115 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Safe Continuation of Apheresis during Pregnancy using the Double-Filtration Plasmapheresis Thermo Mode in a Pregnant Female with Familial Hypercholesterolemia: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevated LDL cholesterol levels and an increased risk of early-onset atherosclerotic cardiovascular disease. In pregnant female with FH, apheresis is the preferred treatment because standard therapeutic agents such as statins are contraindicated during pregnancy. LDL adsorption therapy is commonly used; however, after 27 weeks of gestation, it is often switched to dual filtration plasma exchange (DFPP) due to the significant drop in blood pressure caused by bradykinin production. However, DFPP has limited ability to adapt to the increase in circulating plasma volume associated with pregnancy. Here we discuss the case of a 32-year-old female with homozygous FH who underwent different apheresis strategies during her pregnancies. In her first pregnancy, she continued LDL adsorption therapy using DFPP but ultimately delivered a small-for-gestational-age infant via cesarean section. For her second pregnancy, double-filtration plasmapheresis thermo mode, DF-thermo, was introduced to mitigate the limitations of DFPP and LDL adsorption therapies, such as hypotension during apheresis and albumin loss. By minimizing these complications, DF-thermo allowed for a successful delivery without compromising fetal growth. en-copyright= kn-copyright= en-aut-name=SakurabuYoshimasa en-aut-sei=Sakurabu en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=OkuyamaYuka en-aut-sei=Okuyama en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EtoEriko en-aut-sei=Eto en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakasugiKanako en-aut-sei=Takasugi en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsakawaTomohiko en-aut-sei=Asakawa en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatayamaKatsuyoshi en-aut-sei=Katayama en-aut-mei=Katsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoShugo en-aut-sei=Okamoto en-aut-mei=Shugo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Matsuoka-UchiyamaNatsumi en-aut-sei=Matsuoka-Uchiyama en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiharaChihiro en-aut-sei=Fujihara en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=TakeuchiHidemi en-aut-sei=Takeuchi en-aut-mei=Hidemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UmebayashiRyoko en-aut-sei=Umebayashi en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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=16 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 Obstetrics and Gynecology, Okayama University Hospital 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= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Clinical Engineering Center, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Familial hypercholesterolemia kn-keyword=Familial hypercholesterolemia en-keyword=Double-filtration plasmapheresis thermo-mode kn-keyword=Double-filtration plasmapheresis thermo-mode en-keyword=Pregnancy kn-keyword=Pregnancy END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3 article-no= start-page=400 end-page=408 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=Outcomes following the discontinuation of biologic therapy in patients with severe asthma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Biologic therapies are pivotal in managing severe asthma. Despite their efficacy, some patients discontinue biologics, with varying outcomes. Predictors of successful versus unsuccessful discontinuation remain poorly defined. This study aimed to identify clinical factors associated with post-discontinuation outcomes in a real-world practice.
Methods: This retrospective cohort included adults with severe asthma who had received biologics for at least 12 months and subsequently discontinued therapy for a minimum of three consecutive months. We assessed the effects of baseline blood eosinophilia (?300 cells/μL), residual sputum symptoms during biologic therapy, treatment responsiveness, biologic class, and discontinuation reasons on post-discontinuation asthma exacerbation rates using multivariable Cox models.
Results: A total of 118 patients were analyzed. The Kaplan?Meier analysis estimated a 65 % exacerbation-free probability at 12 months after discontinuation. Factors associated with successful discontinuation included a robust clinical response and absence of exacerbations before cessation. Conversely, baseline eosinophilia, residual sputum symptoms during biologics, and discontinuation due to inadequate therapeutic response or financial burden were associated with post-discontinuation exacerbations. In class-stratified restricted models, persistent sputum remained significantly associated with post-discontinuation exacerbations after stopping anti-IL-5 therapies, while baseline eosinophilia was associated with post-discontinuation exacerbations after stopping anti-IgE or anti-IL-4Rα. Among patients with sputum symptoms or poor-response discontinuation, the overall frequency of exacerbations declined after discontinuation.
Conclusions: Baseline eosinophilia, persistent sputum during therapy, and discontinuation prompted by poor response or cost may serve as risk factors for post-discontinuation exacerbations; however, risk is phenotype- and class-dependent. Careful patient selection and monitoring are essential when considering the discontinuation of biologic treatment. en-copyright= kn-copyright= en-aut-name=NagasakiTadao en-aut-sei=Nagasaki en-aut-mei=Tadao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoHisako en-aut-sei=Matsumoto en-aut-mei=Hisako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IwanagaTakashi en-aut-sei=Iwanaga en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsunagaKazuto en-aut-sei=Matsunaga en-aut-mei=Kazuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SekiyaKiyoshi en-aut-sei=Sekiya en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaradaTomoya en-aut-sei=Harada en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakuraiShogo en-aut-sei=Sakurai en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaradaNorihiro en-aut-sei=Harada en-aut-mei=Norihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KoyaToshiyuki en-aut-sei=Koya en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukunagaKoichi en-aut-sei=Fukunaga en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KanekoTakeshi en-aut-sei=Kaneko en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AsaiKazuhisa en-aut-sei=Asai en-aut-mei=Kazuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KomaseYuko en-aut-sei=Komase en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=GonYasuhiro en-aut-sei=Gon en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaAkihiko en-aut-sei=Tanaka en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SagaraHironori en-aut-sei=Sagara en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SunadomeHironobu en-aut-sei=Sunadome en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NaganoTatsuya en-aut-sei=Nagano en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=NakamuraYoichi en-aut-sei=Nakamura en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=NiimiAkio en-aut-sei=Niimi en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HattoriNoboru en-aut-sei=Hattori en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HajiroTakashi en-aut-sei=Hajiro en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FujimotoHajime en-aut-sei=Fujimoto en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HojoMasayuki en-aut-sei=Hojo en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=MiyaharaNobuaki en-aut-sei=Miyahara en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 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=26 ORCID= en-aut-name=TsujiKimiko en-aut-sei=Tsuji en-aut-mei=Kimiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=SanoAkiko en-aut-sei=Sano en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=HaraguchiRyuta en-aut-sei=Haraguchi en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SanoHiroyuki en-aut-sei=Sano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=MurakiMasato en-aut-sei=Muraki en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=TohdaYuji en-aut-sei=Tohda en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University kn-affil= affil-num=5 en-affil=Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital kn-affil= affil-num=6 en-affil=Department of Multidisciplinary Internal Medicine, Division of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori University kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Shizuoka General Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=10 en-affil=Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine kn-affil= affil-num=11 en-affil=Department of Pulmonology, Yokohama City University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, St.Marianna University School of Medicine, Yokohama Seibu Hospital kn-affil= affil-num=14 en-affil=Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine kn-affil= affil-num=15 en-affil=Department of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University, School of Medicine kn-affil= affil-num=16 en-affil=Department of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University, School of Medicine kn-affil= affil-num=17 en-affil=Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University kn-affil= affil-num=18 en-affil=Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Medical Center for Allergic and Immune Diseases, Yokohama City Minato Red Cross Hospital kn-affil= affil-num=20 en-affil=Department of Respiratory Medicine, Allergy, and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=21 en-affil=Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University kn-affil= affil-num=22 en-affil=Department of Respiratory Medicine, Tenri Hospital kn-affil= affil-num=23 en-affil=Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine kn-affil= affil-num=24 en-affil=Division of Respiratory Medicine, National Center for Global Health and Medicine kn-affil= affil-num=25 en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=26 en-affil=Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science kn-affil= affil-num=27 en-affil=Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University kn-affil= affil-num=28 en-affil=Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine kn-affil= affil-num=29 en-affil=Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine kn-affil= affil-num=30 en-affil=Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine kn-affil= affil-num=31 en-affil=Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital kn-affil= affil-num=32 en-affil=Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine kn-affil= en-keyword=Adult asthma kn-keyword=Adult asthma en-keyword=Biologics kn-keyword=Biologics en-keyword=Discontinuation kn-keyword=Discontinuation en-keyword=Exacerbation kn-keyword=Exacerbation en-keyword=Severe asthma kn-keyword=Severe asthma END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=1 article-no= start-page=35 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=Oral health care during pregnancy to prevent preterm birth and low birth weight: study protocol for a randomized controlled trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Periodontal disease during pregnancy has been associated with an increased risk of preterm birth (PTB) and low birth weight (LBW). However, most previous interventional studies have reported that scaling and root planing (SRP), a form of basic periodontal treatment, is insufficient to effectively prevent PTB and LBW. Recent systematic reviews and meta-analyses suggest that combining SRP with routine use of chlorhexidine gluconate (CHG) mouthwash may reduce the risk of these adverse birth outcomes by approximately half. This study will be among the first randomized controlled trials (RCTs) to evaluate the potential synergistic effects of this combined approach on improving birth outcomes.
Methods This multi-center, three-arm RCT will be conducted at two hospitals in Dhaka and Bogura, Bangladesh, between April 2025 and September 2026. A total of 480 pregnant women less than 20 weeks’ gestation attending antenatal checkups will be recruited. Participants diagnosed with periodontal disease will be randomly assigned to either an intervention group or a positive control group. Participants without periodontal disease will be assigned to a negative control group. The intervention consists of SRP combined with continued use of CHG mouthwash throughout pregnancy. The primary outcome will be the rate of PTB. Secondary outcomes include the birth weight of the newborn baby, maternal periodontal status, and oral health-related quality of life (OHRQoL). Effectiveness will be assessed by comparing outcomes across the study groups.
Discussion The oral health intervention is expected to improve both birth outcomes and maternal oral health. Demonstrating its effectiveness in a real-world setting may support the integration of oral health care into broader maternal, neonatal, and child health strategies, particularly in resource-limited settings.
Trial registration UMIN Clinical Trials Registry. UMIN000057519. Registered on April 4, 2025. https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000065719. en-copyright= kn-copyright= en-aut-name=YasuokaJunko en-aut-sei=Yasuoka en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkadaShunsuke en-aut-sei=Okada en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AlamProdhan MD Rubayet en-aut-sei=Alam en-aut-mei=Prodhan MD Rubayet kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShibanumaAkira en-aut-sei=Shibanuma en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NanishiKeiko en-aut-sei=Nanishi en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoYoko en-aut-sei=Sato en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HossainMd. Zahid en-aut-sei=Hossain en-aut-mei=Md. Zahid kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AmanMusfiqa en-aut-sei=Aman en-aut-mei=Musfiqa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KarimFahmida en-aut-sei=Karim en-aut-mei=Fahmida kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=RaziaSultana en-aut-sei=Razia en-aut-mei=Sultana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=RezwanaRifat en-aut-sei=Rezwana en-aut-mei=Rifat kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=RahmanMd Mahmudur en-aut-sei=Rahman en-aut-mei=Md Mahmudur kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Jahan KhanNusrat en-aut-sei=Jahan Khan en-aut-mei=Nusrat kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakashimaNaoki en-aut-sei=Nakashima en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IslamRafiqul en-aut-sei=Islam en-aut-mei=Rafiqul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KikuchiKimiyo en-aut-sei=Kikuchi en-aut-mei=Kimiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Division of Global Health Sciences, Graduate School of Public Health, St. Luke’s International University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Medical Development Field, Okayama University kn-affil= affil-num=4 en-affil=Department of Orthodontics, Dental Unit, TMSS Medical College & Rafatullah Community Hospital kn-affil= affil-num=5 en-affil=Department of Community and Global Health, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Office of International Academic Affairs, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=8 en-affil=Department of Periodontology and Oral Pathology, Holy Family Red Crescent Medical College Hospital kn-affil= affil-num=9 en-affil=Department of Periodontology, Dental Unit, TMSS Medical College & Rafatullah Community Hospital kn-affil= affil-num=10 en-affil=Department of Obstetrics & Gynecology, Holy Family Red Crescent Medical College Hospital kn-affil= affil-num=11 en-affil=Department of Obstetrics & Gynecology, TMSS Medical College & Rafatullah Community Hospital kn-affil= affil-num=12 en-affil=Department of Molecular and Cellular Biochemistry, Division of Oral Health, Brain Health and Total Health, Faculty of Dental Science, Kyushu University kn-affil= affil-num=13 en-affil=Global Communication Center, Grameen Communications kn-affil= affil-num=14 en-affil=Global Communication Center, Grameen Communications kn-affil= affil-num=15 en-affil=Department of Medical Informatics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=16 en-affil=Division of Healthcare Digital Transformation, Kyushu University kn-affil= affil-num=17 en-affil=Department of Research Promotion, Institute for Asian and Oceanian Studies, Kyushu University kn-affil= en-keyword=Preterm birth kn-keyword=Preterm birth en-keyword=Low birth weight kn-keyword=Low birth weight en-keyword=Oral health kn-keyword=Oral health en-keyword=Periodontal treatment kn-keyword=Periodontal treatment en-keyword=Chlorhexidine gluconate mouthwash kn-keyword=Chlorhexidine gluconate mouthwash en-keyword=Randomized controlled trial kn-keyword=Randomized controlled trial en-keyword=Bangladesh kn-keyword=Bangladesh END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=19 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=Plasma expression levels of microRNA-101 are downregulated in patients with Parkinson’s disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons. Endoplasmic reticulum (ER) stress contributes to PD pathogenesis, with the ER-associated degradation (ERAD) system playing a protective role. HRD1, an ER-resident ubiquitin ligase, and its stabilizer SEL1L are involved in ERAD and neuronal survival. This study investigated alterations in the plasma levels of microRNA-101 (miR-101), which targets SEL1L, in patients with PD, and its potential role as a biomarker.
Results Plasma miR-101 levels in patients with PD significantly decreased compared with those in healthy controls. Receiver operating characteristic curve analysis demonstrated that miR-101 could moderately discriminate patients with PD from healthy individuals (area under the curve?=?0.781, 95% confidence interval?=?0.547?1.00). The optimal cutoff, as determined by the Youden index, was 0.737 (expression ratio relative to that in the healthy control group), yielding a sensitivity of 50% and specificity of 100%. These results suggested that reduced plasma miR-101 expression may reflect the pathophysiological state of PD, and miR-101 has potential as minimally invasive biomarker for PD. en-copyright= kn-copyright= en-aut-name=OmuraTomohiro en-aut-sei=Omura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiguchiHiroki en-aut-sei=Nishiguchi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanedaHaruka en-aut-sei=Kaneda en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 ORCID= en-aut-name=SakaneToshiyasu en-aut-sei=Sakane en-aut-mei=Toshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=2 en-affil=Department of Pharmacy, Kobe University Hospital 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 Pharmacy, Kobe University Hospital kn-affil= affil-num=6 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pharmaceutical Technology, Kobe Pharmaceutical University kn-affil= affil-num=8 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= en-keyword=Parkinson’s disease kn-keyword=Parkinson’s disease en-keyword=microRNA kn-keyword=microRNA en-keyword=Endoplasmic reticulum stress kn-keyword=Endoplasmic reticulum stress en-keyword=HRD1 kn-keyword=HRD1 en-keyword=SEL1L kn-keyword=SEL1L 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=20260707 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sex differences and contest experience shape walking patterns in the broad-horned flour beetle en-subtitle= kn-subtitle= en-abstract= kn-abstract=Animal movement patterns vary widely across species, and sex differences are often expected because males typically need to encounter multiple females and acquire resources. In species where males engage in male?male combat using exaggerated weapons, variation in weapon size and contest outcomes is known to influence male reproductive strategies, and may therefore also affect movement behavior. However, sex-specific and male-specific differences in locomotor behavior, particularly in relation to weapon size and social interactions, remain poorly understood. Here, we investigated walking trajectories in the broad-horned flour beetle (Gnatocerus cornutus) to test for (1) sex differences, (2) associations between male weapon size and movement behavior, and (3) the effects of male?male combat. Males exhibited more tortuous and localized movement, whereas females showed straighter and more spatially extensive trajectories. Following contests, all males showed a reduction in activity regardless of contest outcome; however, winners and losers exhibited divergent changes in movement patterns, with winners showing straighter and more spatially extensive trajectories and losers showing more tortuous and localized trajectories. In contrast, body-size-corrected weapon size was not associated with any aspect of walking behavior. These results indicate that locomotor behavior in G. cornutus varies with sex and contest experience, and that variation in walking behavior is more closely associated with social experience than with weapon morphology. en-copyright= kn-copyright= en-aut-name=MatsumuraKentarou en-aut-sei=Matsumura en-aut-mei=Kentarou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HashiokaSora en-aut-sei=Hashioka en-aut-mei=Sora kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagayaNaohisa en-aut-sei=Nagaya en-aut-mei=Naohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujisawaRyusuke en-aut-sei=Fujisawa en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= affil-num=1 en-affil=Graduate School of Arts and Sciences, The University of Tokyo 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 Information Science and Engineering, Kyoto Sangyo University kn-affil= affil-num=4 en-affil=Faculty of Environmental Engineering, University of Kitakyushu, kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Turning angle kn-keyword=Turning angle en-keyword= Acceleration kn-keyword= Acceleration en-keyword=Male-male combat kn-keyword=Male-male combat en-keyword=Weapon kn-keyword=Weapon en-keyword=ANTAM kn-keyword=ANTAM END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260722 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=裏表紙・英文目次 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue=1 article-no= start-page=47 end-page=59 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260722 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Die Agrarstruktur in Sachsen im 19. Jahrhundert（6） kn-title=19世紀ザクセンの土地制度（６） en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MatsuoNobushige en-aut-sei=Matsuo en-aut-mei=Nobushige kn-aut-name=松尾展成 kn-aut-sei=松尾 kn-aut-mei=展成 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学名誉教授 END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue=1 article-no= start-page=33 end-page=45 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260722 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Historical Shifts in the Scope of the Biological Concept in IAS 41 and AASB 1037 kn-title=IAS41 と AASB1037 における生物の範囲設定に関する歴史的変遷 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YoshidaKohei en-aut-sei=Yoshida en-aut-mei=Kohei kn-aut-name=吉田浩平 kn-aut-sei=吉田 kn-aut-mei=浩平 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=東京大学大学院総合文化研究科博士課程 END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue=1 article-no= start-page=21 end-page=32 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260722 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The Current State and Challenges of the Academic Economics Job Market in China: An Analysis of Incentive Structures Based on Crowdsourced Data kn-title=中国における経済学アカデミック・ジョブマーケットの現状と課題 ―クラウドソーシング・データに基づくインセンティブ構造の分析― en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=WangRuiting en-aut-sei=Wang en-aut-mei=Ruiting kn-aut-name=王睿霆 kn-aut-sei=王 kn-aut-mei=睿霆 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学経済学部 END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue=1 article-no= start-page=1 end-page=19 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260722 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Visualizing University Library Structures through a Library Schema: A Conceptual Framework for Knowledge Creation in Academic Libraries kn-title=ライブラリ・スキーマによる大学図書館構造の可視化と知識創造 ―共有認知の形成に基づく研究枠組みの構築― en-subtitle= kn-subtitle= en-abstract= kn-abstract=　This study proposes a theoretical framework for understanding the relationship between the structural representation of university libraries and knowledge creation. In recent years, university libraries have experienced significant transformations due to the digitization of scholarly information, the expansion of research data management, and the increasing importance of learning support services. As their functions diversify, it has become increasingly difficult to comprehensively understand the structure and roles of university libraries.
　To address this issue, this study focuses on the concept of a library schema, which represents the structural relationships among the elements that constitute a library, including people, resources, services, and activities. While previous research has discussed methods for organizing library components, little attention has been paid to how structural understanding of libraries contributes to knowledge creation and service value.
　Drawing on schema theory, shared cognition in organizational studies, and the knowledge creation theory of Nonaka and Takeuchi, this study constructs a conceptual framework linking library schema visualization, shared cognition, interaction, knowledge creation processes, and library service value. The framework proposes that visualization of library structure through a library schema promotes shared cognition among librarians and users, which in turn facilitates interactions that activate knowledge creation processes. These processes ultimately contribute to the creation of library service value that supports learning and research activities.
　Furthermore, the framework introduces two moderating factors: schema representation methods and operational constraints of library management. Based on this framework, six research propositions are presented.
　By integrating concepts from library and information science with knowledge management theory, this study contributes to the theoretical understanding of university libraries as knowledge infrastructures and provides a foundation for future empirical research on knowledge creation in library environments. en-copyright= kn-copyright= en-aut-name=KobayashiKensuke en-aut-sei=Kobayashi en-aut-mei=Kensuke kn-aut-name=小林健輔 kn-aut-sei=小林 kn-aut-mei=健輔 aut-affil-num=1 ORCID= en-aut-name=MiyazakiSatoru en-aut-sei=Miyazaki en-aut-mei=Satoru kn-aut-name=宮崎悟 kn-aut-sei=宮崎 kn-aut-mei=悟 aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=岡山大学研究・イノベーション共創機構 affil-num=2 en-affil= kn-affil=岡山大学学術研究院社会文化科学学域 END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260722 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=表紙・目次 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=1 article-no= start-page=128 end-page=135 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=Developing and Implementing a Disaster Prevention Game to Enhance Local Understanding en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study developed and implemented a local disaster prevention sugoroku-style game to address challenges in preserving and transmitting regional knowledge in areas with high population mobility. Many Japanese communities face both natural and social vulnerabilities, and effective disaster education requires linking hazard knowledge with local characteristics. Conducted at Sonan Junior High School in Okayama, the project combined lectures, workshops, and a community engagement event. Students learned about regional topography, land use, and disaster history and used this knowledge to design quizzes, rules, and disaster scenarios for the game. The final sugoroku set included a map-based board, thematic quiz areas, and preparedness item cards, enabling players to predict damage and consider appropriate actions. After creating the game, students shifted from identifying familiar landmarks to describing concrete disaster impacts such as liquefaction or infrastructure collapse. Interaction with local residents further enriched learning through shared experiences. The model proved feasible in terms of time and cost, and its structure is easily adaptable to other regions by incorporating local information. The findings suggest that this participatory, place-based approach enhances imagination, self-efficacy, and intergenerational knowledge transfer, contributing to community-wide disaster preparedness. Future studies will examine long-term educational impacts and broader regional applications. en-copyright= kn-copyright= en-aut-name=ShirokaneMiri en-aut-sei=Shirokane en-aut-mei=Miri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaAiri en-aut-sei=Yamada en-aut-mei=Airi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MisawaRyo en-aut-sei=Misawa en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MattaNobuhisa en-aut-sei=Matta en-aut-mei=Nobuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Okayama University kn-affil= affil-num=3 en-affil=Okayama University kn-affil= affil-num=4 en-affil=Okayama University kn-affil= en-keyword=disaster education kn-keyword=disaster education en-keyword=local disaster knowledge kn-keyword=local disaster knowledge en-keyword=disaster literacy kn-keyword=disaster literacy en-keyword=damage estimation abilities kn-keyword=damage estimation abilities en-keyword=community resilience kn-keyword=community resilience END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue= article-no= start-page=105422 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=Pathological features of residual head and neck cancer after near-infrared photoimmunotherapy: implications of an unfavorable tumor immune microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: Near-infrared photoimmunotherapy has been approved in Japan for unresectable locally advanced or recurrent head and neck cancer. While this therapy theoretically induces selective necrosis of epidermal growth factor receptor-expressing tumor cells following administration of cetuximab sarotalocan sodium and irradiation with 690-nm light, residual disease is not uncommon in clinical practice. The mechanisms underlying such persistence remain poorly understood.
Methods: We examined two patients with head and neck squamous cell carcinoma who underwent salvage resection due to residual disease after four cycles of near-infrared photoimmunotherapy. Resected specimens were subjected to histopathological evaluation, including immunohistochemistry for epidermal growth factor receptor, cluster of differentiation 8, programmed cell death protein 1, and forkhead box P3 proteins.
Results: In both cases, residual tumor cells were predominantly localized in the superficial mucosal layers, while deeper layers were replaced by fibrosis. All residual tumors retained expression of epidermal growth factor receptor. Lymphocytic infiltration was sparse, with scattered cluster of differentiation 8-positive cells but few programmed cell death protein 1-positive or forkhead box P3-positive lymphocytes. These findings suggest that the tumor microenvironment surrounding residual tumors may have been unfavorable for the induction of robust antitumor immune responses.
Conclusion: Residual tumors after near-infrared photoimmunotherapy can occur despite adequate laser irradiation and epidermal growth factor receptor expression. Our observations imply that insufficient immune activation within the tumor microenvironment may contribute to treatment resistance. Further characterization of the post-photoimmunotherapy tumor microenvironment will be essential to better understand treatment mechanisms and to optimize therapeutic efficacy. en-copyright= kn-copyright= en-aut-name=MakinoTakuma en-aut-sei=Makino en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaoiYuto en-aut-sei=Naoi en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=NIR-PIT kn-keyword=NIR-PIT en-keyword=EGFR kn-keyword=EGFR en-keyword=CD8 kn-keyword=CD8 en-keyword=PD-1 kn-keyword=PD-1 en-keyword=FOXP3 kn-keyword=FOXP3 en-keyword=Tumor microenvironment kn-keyword=Tumor microenvironment en-keyword=Photoimmunotherapy kn-keyword=Photoimmunotherapy en-keyword=Head and neck cancer kn-keyword=Head and neck cancer END start-ver=1.4 cd-journal=joma no-vol=112 cd-vols= no-issue=3 article-no= start-page=104642 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=Relationship between the Hounsfield Unit value of the greater trochanter and the risk of greater trochanteric fractures in anterolateral muscle-sparing minimally invasive total hip arthroplasty en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: No previous studies have investigated the association between the risk of greater trochanteric fractures and the Hounsfield Unit (HU) of the greater trochanter in muscle-sparing minimally invasive total hip arthroplasty (MIS-THA). This study aimed to investigate the risk factors for greater trochanteric fractures in anterolateral MIS-THA.
Hypothesis: Lower HU values of the greater trochanter are associated with a higher risk of intraoperative and early postoperative greater trochanteric fractures.
Patients and methods: This single-center retrospective observational study included 223 patients (257 hips) who underwent primary THA for osteoarthritis or osteonecrosis between January 2010 and August 2024 using a minimally invasive anterolateral approach in the lateral position. All surgeries were performed by four surgeons. Preoperative CT was used to reconstruct coronal sections including the femoral head center and proximal femoral axis, and cancellous HU values of the greater trochanter were measured. Postoperative CT (1 week) with metal artifact reduction was routinely performed; fractures were defined as cortical fracture lines on 3D-reconstructed CT and assessed by two independent orthopedic surgeons. Patients were divided into two groups according to the presence or absence of fractures.
Results: The incidence of greater trochanteric fractures was 6.6% (17/257 hips). Twelve of these fractures (70.6%) were recognized intraoperatively or immediately postoperatively. Full hydroxyapatite (HA)-coated stems were associated with an increased fracture risk compared with other designs (relative risk [RR], 2.68; 95% CI, 1.07?6.68). Age, sex, BMI, ASA physical status, and diagnosis were not significantly associated with fractures. Multivariate analysis identified lower HU values (odds ratio [OR], 0.973; p < 0.0001) and full HA-coated stems (OR, 13.3; p = 0.04) as independent predictors. Receiver operating characteristic (ROC) analysis determined an optimal cut-off of 72.0 HU (sensitivity, 0.941; specificity, 0.742), with a value ?72.0 HU demonstrating high predictive power (RR, 36.7; p < 0.0001).
Conclusion: Preoperative measurement of HU values in the greater trochanter is a useful screening tool for identifying patients at increased risk of fractures in anterolateral MIS-THA. While an HU value of ? 72.0 necessitates careful intraoperative management and increased vigilance, it should be interpreted as an indicator of risk rather than a definitive predictor of fracture due to its moderate specificity.
Level of evidence: IV; retrospective study. en-copyright= kn-copyright= en-aut-name=OkudaRyuichiro en-aut-sei=Okuda en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TetsunagaTomonori en-aut-sei=Tetsunaga en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaKazuki en-aut-sei=Yamada en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TetsunagaTomoko en-aut-sei=Tetsunaga en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=MasadaYasutaka en-aut-sei=Masada en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoTetsuya en-aut-sei=Yamamoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumotoShin en-aut-sei=Matsumoto en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkazakiYuki en-aut-sei=Okazaki en-aut-mei=Yuki 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, Okayama University kn-affil= affil-num=2 en-affil=Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Faculty of Medical Development Field, Okayama University kn-affil= affil-num=4 en-affil=Department of Sports Medicine, Faculty 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, Okayama University kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= en-keyword=Periprosthetic fracture kn-keyword=Periprosthetic fracture en-keyword=Anterolateral approach kn-keyword=Anterolateral approach en-keyword=Direct anterior approach kn-keyword=Direct anterior approach en-keyword=Bone density kn-keyword=Bone density en-keyword=Hip prosthesis kn-keyword=Hip prosthesis END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=3482 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Atomic imaging for hydrogen and boron aggregates in boron-doped diamond by spectro-photoelectron holography en-subtitle= kn-subtitle= en-abstract= kn-abstract=The electrical properties of diamond are modulated by impurity doping. Isolated substitutional boron atoms introduce holes; however, the fraction of electrically inactive boron atoms increases at higher doping concentrations. This has been attributed to boron aggregation and hydrogen passivation, although their structural identification based on atomic arrangement has yet to be experimentally verified. Here we show the origin of multiple chemical states in homoepitaxially grown boron-doped diamond thin films by analyzing the atomic environment of boron using spectro-photoelectron holography. Our analysis identifies boron dimers and boron-hydrogen complexes, with hydrogen occupying different atomic sites that give rise to distinct chemical shifts. These results suggest that hydrogen incorporation during growth leads to passivation of boron acceptors. We demonstrate that photoelectron holography serves as a promising tool for imaging hydrogen as well as determining the atomic sites of dopants. en-copyright= kn-copyright= en-aut-name=TomitaHiroto en-aut-sei=Tomita en-aut-mei=Hiroto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HosodaWataru en-aut-sei=Hosoda en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaniguchiTakumi en-aut-sei=Taniguchi en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiwaraHirokazu en-aut-sei=Fujiwara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KataokaNoriyuki en-aut-sei=Kataoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KageuraTaisuke en-aut-sei=Kageura en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakanoYoshihiko en-aut-sei=Takano en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaradaHiroshi en-aut-sei=Kawarada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OguchiTamio en-aut-sei=Oguchi en-aut-mei=Tamio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YokoyaTakayoshi en-aut-sei=Yokoya en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsushitaTomohiro en-aut-sei=Matsushita en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Graduate School of Science and Technology, Nara Institute of Science and Technology 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=Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=5 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=6 en-affil=Sensing Technology Research Institute, National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=7 en-affil=Research Center for Materials Nanoarchitectonics, National Institute for Materials Science kn-affil= affil-num=8 en-affil=Faculty of Science and Engineering, Waseda University kn-affil= affil-num=9 en-affil=Center for Spintronics Research Network, The University of Osaka kn-affil= affil-num=10 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Science and Technology, Nara Institute of Science and Technology kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=16760 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=Asthma-like bronchodilator responsiveness in patients with neuronal intranuclear inclusion disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative condition characterized by the presence of intranuclear inclusions in neuronal and visceral cells. Patients with NIID can present respiratory symptoms; however, data on pulmonary functions in NIID are lacking. This study investigated the respiratory conditions in NIID patients diagnosed with histopathological and genetic studies. We conducted two spirometries before and after administrating the bronchodilator in NIID patients with asthmatic histories or symptoms. We statistically compared pre- and post-measured values including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF). Before two spirometries, we also measured fractional concentration of exhaled nitric oxide (FeNO), if possible. Of the 51finally enrolled patients, 17 (33.3%, 95% CI 20.8% to 47.9%) patients had asthmatic histories or symptoms, and 14 patients received two spirometries. After administrating the bronchodilator, FEV1 and PEF significantly increased by 150 mL (6.01%, p?=?0.002) and 260 mL/s (6.72%, p?=?0.017), respectively. The median (interquartile range) of FeNO measured in nine patients was 15 (10?21) ppb. Patients with NIID have airflow reversibility like asthma. This condition appears to be less associated with airway inflammation and may be related to autonomic dysfunction. en-copyright= kn-copyright= en-aut-name=TaharaDaisuke en-aut-sei=Tahara en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TaharaNao en-aut-sei=Tahara en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TamaiChisato en-aut-sei=Tamai en-aut-mei=Chisato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkagiAkio en-aut-sei=Akagi en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RikuYuichi en-aut-sei=Riku en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyaharaHiroaki en-aut-sei=Miyahara en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobayashiRei en-aut-sei=Kobayashi en-aut-mei=Rei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkadaHisashi en-aut-sei=Okada en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawamotoMichi en-aut-sei=Kawamoto en-aut-mei=Michi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiiJunko en-aut-sei=Ishii en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamazakiHiroki en-aut-sei=Yamazaki en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KurashigeTakashi en-aut-sei=Kurashige en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SugiyamaAtsuhiko en-aut-sei=Sugiyama en-aut-mei=Atsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NagaishiAkiko en-aut-sei=Nagaishi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NishidaKatsuya en-aut-sei=Nishida en-aut-mei=Katsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SugieKazuma en-aut-sei=Sugie en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FukudomeTakayasu en-aut-sei=Fukudome en-aut-mei=Takayasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HasegawaKazuko en-aut-sei=Hasegawa en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 ORCID= en-aut-name=KoikeHaruki en-aut-sei=Koike en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KasaiTakashi en-aut-sei=Kasai en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MizunoToshiki en-aut-sei=Mizuno en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=AndoMasahiro en-aut-sei=Ando en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HiguchiYujiro en-aut-sei=Higuchi en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=TanakaFumiaki en-aut-sei=Tanaka en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IzumiYuishin en-aut-sei=Izumi en-aut-mei=Yuishin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=SobueGen en-aut-sei=Sobue en-aut-mei=Gen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=IwasakiYasushi en-aut-sei=Iwasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=ItoSatoru en-aut-sei=Ito en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SoneJun en-aut-sei=Sone en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=2 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=3 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=4 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=5 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=6 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=7 en-affil=Department of Neurology, NHO Nagoya Medical Center kn-affil= affil-num=8 en-affil=Department of Neurology, NHO Nagoya Medical Center kn-affil= affil-num=9 en-affil=Department of Neurology, Kobe City Medical Center General Hospital kn-affil= affil-num=10 en-affil=Department of Neurology, Kobe City Medical Center General Hospital kn-affil= affil-num=11 en-affil=Department of Neurology, Tokushima University Graduate School of Biomedical Science kn-affil= affil-num=12 en-affil=Department of Neurology, NHO Kure Medical Center and Chugoku Cancer Center kn-affil= affil-num=13 en-affil=Department of Neurology, Chiba University kn-affil= affil-num=14 en-affil=Department of Neurology, NHO Nagasaki Kawatana Medical Center kn-affil= affil-num=15 en-affil=Department of Neurology, NHO Hyogo Chuo National Hospital kn-affil= affil-num=16 en-affil=Department of Neurology, Nara Medical University Hospital kn-affil= affil-num=17 en-affil=Department of Neurology, NHO Nagasaki Kawatana Medical Center kn-affil= affil-num=18 en-affil=Department of Neurology, NHO Sagamihara National Hospital kn-affil= affil-num=19 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=20 en-affil=Department of Neurology, Saga University kn-affil= affil-num=21 en-affil=Department of Neurology, Kyoto Prefectural University of Medicine kn-affil= affil-num=22 en-affil=Department of Neurology, Kyoto Prefectural University of Medicine kn-affil= affil-num=23 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=24 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=25 en-affil=Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine kn-affil= affil-num=26 en-affil=Department of Neurology, Tokushima University Graduate School of Biomedical Science kn-affil= affil-num=27 en-affil=Aichi Medical University kn-affil= affil-num=28 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=29 en-affil=Division of Respiratory Medicine and Allergology, Department of Internal Medicine, School of Medicine, Aichi Medical University kn-affil= affil-num=30 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= en-keyword=Asthma kn-keyword=Asthma en-keyword=Autonomic dysfunction kn-keyword=Autonomic dysfunction en-keyword=Cough kn-keyword=Cough en-keyword=Neuronal intranuclear inclusion disease kn-keyword=Neuronal intranuclear inclusion disease en-keyword=NOTCH2NLC kn-keyword=NOTCH2NLC en-keyword=Pulmonary function kn-keyword=Pulmonary function END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=838 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260418 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=In vivo activities of E1 elements in the insulin promoter en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this study, we evaluated the in vivo activity of the E1 element within the insulin promoter region. While we successfully obtained mice carrying a deletion exclusively in the E1 element of Ins2 (2E mice), we were unable to obtain mice with a deletion limited to the E1 element of Ins1. To assess the role of the E1 element in Ins1, we compared the mice carrying deletions in the GG2-GG1/A2-C1 elements with or without an additional E1 element deletion (1GC/1GCE mice). 1GCE2E mice developed diabetes. In contrast, 1GCE23 mice (without deletion in the E1 element of Ins2) did not develop diabetes, suggesting that the E1 element of Ins2 is critical for transcriptional regulation. Furthermore, 1GC2E mice (presence of the E1 element of Ins1) developed diabetes. However, the severity of the disease was milder in 1GC2E mice than in 1GCE2E mice, indicating that the E1 element of Ins1 also contributes to transcriptional regulation. These data suggest that the E1 elements in both Ins1/2 promoters are regulated for the in vivo transcription of insulin genes in mice. 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