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=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=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=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=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 < 25% (60.3% vs. 29.4%; adjusted odds ratio 2.20, 95% confidence interval 1.08–4.48), 5 Gy (V5) ≥ median (37.85%) versus < median (51.5% vs. 27.2%; 1.79, 1.07–3.00), and grade 1 ILD before durvalumab administration versus no ILD (50.0% vs. 37.6%; 2.11, 1.07–4.17).
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=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-naïve 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-naïve 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 Højby en-aut-sei=Rasmussen en-aut-mei=Michael Højby 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=SværkeClaus en-aut-sei=Sværke 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=74 cd-vols= no-issue=3 article-no= start-page=76 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel combination therapy for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma: a systematic review and network meta-analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent phase 3 randomized controlled trials (RCTs) demonstrate the promising impact of immune checkpoint inhibitor (ICI)-based combination therapies on locally advanced or metastatic urothelial carcinoma (UC). However, comparative data on the efficacy and toxicity of different ICI-based combinations are lacking. This study aims to compare the efficacy of first-line ICI-based combination therapies for locally advanced or metastatic UC using phase 3 RCT data. In November 2023, three databases were searched for RCTs evaluating oncological outcomes in patients with locally advanced or metastatic UC who were treated with first-line ICI-based combination therapies. Network meta-analysis (NMA) was conducted to compare outcomes, including overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), and treatment-related adverse events (TRAEs). Subgroup analyses were based on PD-L1 status and cisplatin eligibility. The NMA included five RCTs. Enfortumab vedotin (EV) + pembrolizumab ranked the highest for improving OS (100%), PFS (100%), ORR (96%), and CRR (96%), followed by nivolumab + chemotherapy. EV + pembrolizumab combination superiority held across PD-L1 status and cisplatin eligibility. In patients who are cisplatin-eligible, EV + pembrolizumab significantly improved OS (HR: 0.68, 95%CI 0.47–0.99) and PFS (HR: 0.67, 95%CI 0.49–0.92) compared to nivolumab + chemotherapy. Durvalumab + tremelimumab was the safest combination for severe TRAEs, and EV + pembrolizumab ranked second. Our analyses support EV + pembrolizumab combination as a first-line treatment for locally advanced or metastatic UC. Thus, EV + pembrolizumab may become a guideline-changing standard treatment. en-copyright= kn-copyright= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=LaukhtinaEkaterina en-aut-sei=Laukhtina en-aut-mei=Ekaterina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=RajwaPawel en-aut-sei=Rajwa en-aut-mei=Pawel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=QuhalFahad en-aut-sei=Quhal en-aut-mei=Fahad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=PradereBenjamin en-aut-sei=Pradere en-aut-mei=Benjamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukuokayaWataru en-aut-sei=Fukuokaya en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwataniKosuke en-aut-sei=Iwatani en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=PichlerRenate en-aut-sei=Pichler en-aut-mei=Renate kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TeohJeremy Yuen-Chun en-aut-sei=Teoh en-aut-mei=Jeremy Yuen-Chun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MoschiniMarco en-aut-sei=Moschini en-aut-mei=Marco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KrajewskiWojciech en-aut-sei=Krajewski en-aut-mei=Wojciech kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MikiJun en-aut-sei=Miki en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ShariatShahrokh F. en-aut-sei=Shariat en-aut-mei=Shahrokh F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KimuraTakahiro en-aut-sei=Kimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=European Association of Urology–Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU) en-aut-sei=European Association of Urology–Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU) en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=2 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=3 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=4 en-affil=Department of Urology, 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, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=7 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=8 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=9 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=10 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=11 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck kn-affil= affil-num=13 en-affil=S.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong kn-affil= affil-num=14 en-affil=Department of Urology, San Raffaele Hospital and Scientific Institute kn-affil= affil-num=15 en-affil=Department of Minimally Invasive and Robotic Urology, Wrocław Medical University kn-affil= affil-num=16 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=17 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=18 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=19 en-affil= kn-affil= en-keyword=Chemotherapy kn-keyword=Chemotherapy en-keyword=Enfortumab vedotin kn-keyword=Enfortumab vedotin en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors en-keyword=Metastasis kn-keyword=Metastasis en-keyword=Urothelial carcinoma kn-keyword=Urothelial carcinoma 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=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=2 cd-vols= no-issue=3 article-no= start-page=45 end-page=56 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241130 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relationship between food security and dietary habits and subjective sense of health and subjective sense of well-being among residents of large-scale housing complexes in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: This study aimed to determine the relationship between food security and dietary habits and subjective health and subjective well-being among residents of a large-scale housing complex in Japan. Methods: This study used a cross-sectional design through a self-administered questionnaire survey. The study subjects were residents of Mukogawa Danchi in Nishinomiya City, Hyogo Prefecture, Japan, and data from 515 households out of 6,857 total dwelling units were used for the analysis. Food security status (HFSSM), dietary diversity score (HDDS), diet, eating behavior, subjective sense of health, and subjective sense of well-being were examined using logistic regression analysis. Results: Food insecurity was negatively associated with household dietary diversity scores (OR [95%CI]:0.49 [0.24–0.98] p = 0.044). Similarly, food insecurity was negatively associated with having a nutritionally balanced diet and having a satisfactory amount of food. There was also a negative association with family meals. There was a negative association between food insecurity and a subjective sense of health and a negative association (0.35 [0.15–0.78] p = 0.011) with a subjective sense of well-being among those aged 65 and older. Conclusions: In a large-scale housing complex in Japan, inadequate dietary intake was observed in food-insecure households; they ate meals less frequently with their families. Additionally, residents experiencing food insecurity tended to have lower subjective health and subjective well-being, depending on their age. en-copyright= kn-copyright= en-aut-name=WakimotoKeiko en-aut-sei=Wakimoto en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Yokoro-HisanariMiyuki en-aut-sei=Yokoro-Hisanari en-aut-mei=Miyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhtsuboAkira en-aut-sei=Ohtsubo en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiTatsuya en-aut-sei=Fujii en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoJotaro en-aut-sei=Kato en-aut-mei=Jotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OgasawaraHitoshi en-aut-sei=Ogasawara en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KudoDaisuke en-aut-sei=Kudo en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FukuiMinae en-aut-sei=Fukui en-aut-mei=Minae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujitaYuichi en-aut-sei=Fujita en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=School of Food Sciences and Nutrition, Mukogawa Women’s University kn-affil= affil-num=2 en-affil=Faculty of Education, Okayama University kn-affil= affil-num=3 en-affil=Community Liaison Division for Education and Research, Mukogawa Women’s University kn-affil= affil-num=4 en-affil=School of Education, Mukogawa Women’s University kn-affil= affil-num=5 en-affil=School of Letters, Mukogawa Women’s University kn-affil= affil-num=6 en-affil=School of Nursing, Mukogawa Women’s University kn-affil= affil-num=7 en-affil=School of Nursing Science, Meiji University of Integrative Medicine kn-affil= affil-num=8 en-affil=Ichikan Nursing Development center for Diversity, Kobe City College of Nursing kn-affil= affil-num=9 en-affil=School of Nursing, Mukogawa Women’s University kn-affil= en-keyword=food security kn-keyword=food security en-keyword=dietary quality kn-keyword=dietary quality en-keyword=eating behavior kn-keyword=eating behavior en-keyword=self-rated health kn-keyword=self-rated health END start-ver=1.4 cd-journal=joma no-vol=102 cd-vols= no-issue=3 article-no= start-page=438 end-page=450 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Curve Fitting Method for Analyzing Starch Granule Size Distributions in Cereals en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Objectives: The size distribution of starch granules is an important factor in determining the functional and nutritional properties of starch. However, a simple, standardized method for their analysis is lacking. Here, we developed an approach for estimating granule size parameters using a Python script that fits curves to volumetric granule size distributions generated using a Coulter counter.
Findings: The bimodal size distribution of starch from most wheat and barley cultivars could be best described with a mixed distribution curve. A log-normal distribution was fitted to the small B-type granules, and a normal distribution was fitted to the large A-type granules, allowing estimation of their relative abundance and size parameters despite their overlapping size distributions. However, the optimal fitting is altered in wheat mutants with large perturbations in B-type granule content. In maize and rice, which have unimodal granule size distributions, size parameters were calculated by fitting a single normal distribution.
Conclusions: Curve fitting is an effective approach for estimating starch granule size parameters in diverse cereals, particularly the Triticeae with A- and B-type granules.
Significance and Novelty: We provide new tools and guidelines for the quantitative analysis of granule size in cereals. en-copyright= kn-copyright= en-aut-name=McNellyRose en-aut-sei=McNelly en-aut-mei=Rose kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BriffaAmy en-aut-sei=Briffa en-aut-mei=Amy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YiasoumiGeorgia en-aut-sei=Yiasoumi en-aut-mei=Georgia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UauyCristobal en-aut-sei=Uauy en-aut-mei=Cristobal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsushimaRyo en-aut-sei=Matsushima en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SeungDavid en-aut-sei=Seung en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=John Innes Centre kn-affil= affil-num=2 en-affil=John Innes Centre kn-affil= affil-num=3 en-affil=John Innes Centre kn-affil= affil-num=4 en-affil=John Innes Centre kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=John Innes Centre kn-affil= 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=14 cd-vols= no-issue=3 article-no= start-page=276 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250307 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Influence of Educational Films on Antiviral Prescription for COVID-19: Insights from Web-Based Survey in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Prescribing antiviral agents for severe acute respiratory syndrome coronavirus 2 requires careful consideration based on the patient’s risk factors for severe disease progression and their vaccination status. However, effective interventions ensuring the appropriate use of antiviral agents by physicians have yet to be fully established. Thus, this study evaluated the impact of an educational film on antiviral prescription rates for coronavirus disease 2019 (COVID-19). Methods: This prospective, nationwide, web-based survey enrolled 1500 physicians. They were instructed to view a short educational film and assess the necessity of prescribing antiviral agents in 16 fictitious scenarios featuring adult patients with COVID-19 with varying risk factors for severe disease and vaccination statuses. We compared the antiviral prescription rates before and after viewing the educational film. Results: There was a significant increase in the antiviral prescription rates after viewing the educational film, particularly nirmatrelvir/ritonavir prescribed in cases involving immunocompromised patients (from 31.3% to 49.4%) and those with obesity (from 15.1% to 33.7%) who were unvaccinated and had no risk of drug interactions. However, viewing the educational film made little to no impact on the prescription rates for the patients with hypertension and hyperlipidemia or those with no underlying conditions. Conclusions: Short educational films may promote the appropriate use of antiviral agents for COVID-19. However, their impact on altering prescription behavior appears limited and varies according to the clinical context. en-copyright= kn-copyright= en-aut-name=KomiyaKosaku en-aut-sei=Komiya en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiwaraAkihiko en-aut-sei=Hagiwara en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShindoYuichiro en-aut-sei=Shindo en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakamatsuKazufumi en-aut-sei=Takamatsu en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimuraNaoki en-aut-sei=Nishimura en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakechiYukako en-aut-sei=Takechi en-aut-mei=Yukako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=TakazonoTakahiro en-aut-sei=Takazono en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IzumiShinyu en-aut-sei=Izumi en-aut-mei=Shinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GotohShimpei en-aut-sei=Gotoh en-aut-mei=Shimpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakaoSeiichiro en-aut-sei=Sakao en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IzumoTakehiro en-aut-sei=Izumo en-aut-mei=Takehiro 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=YateraKazuhiro en-aut-sei=Yatera en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KakeyaHiroshi en-aut-sei=Kakeya en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShibataYoko en-aut-sei=Shibata en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TomiiKeisuke en-aut-sei=Tomii en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 ORCID= en-aut-name=SasakiYuka en-aut-sei=Sasaki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HiraiToyohiro en-aut-sei=Hirai en-aut-mei=Toyohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YokoyamaAkihito en-aut-sei=Yokoyama en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MukaeHiroshi en-aut-sei=Mukae en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=OguraTakashi en-aut-sei=Ogura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine kn-affil= affil-num=2 en-affil=Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Nagoya University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, National Center for Global Health and Medicine kn-affil= affil-num=6 en-affil=Iki-iki Clinic kn-affil= affil-num=7 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, National Center for Global Health and Medicine kn-affil= affil-num=10 en-affil=Department of Clinical Application, Center for iPS Cell, Research and Application, Kyoto University kn-affil= affil-num=11 en-affil=Department of Pulmonary Medicine, School of Medicine, International University of Health and Welfare kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Japanese Red Cross Medical Center kn-affil= affil-num=13 en-affil=Division of Infectious, Respiratory, and Digestive Medicine, First Department of Internal Medicine, University of the Ryukyus Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health, Japan kn-affil= affil-num=15 en-affil=Department of Infection Control Science, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Pulmonary Medicine, Fukushima Medical University School of Medicine kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Kobe City Medical Center General Hospital kn-affil= affil-num=18 en-affil=Department of Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine kn-affil= affil-num=19 en-affil=Center for Pulmonary Disease, National Hospital Organization Tokyo Hospital kn-affil= affil-num=20 en-affil=Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University kn-affil= affil-num=21 en-affil=Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University kn-affil= affil-num=22 en-affil=Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=23 en-affil=Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center kn-affil= en-keyword=antiviral kn-keyword=antiviral en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=prescription kn-keyword=prescription en-keyword=education kn-keyword=education 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=75 cd-vols= no-issue=3 article-no= start-page=002139 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260313 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Investigation of carbapenem-hydrolysing Klebsiella oxytoca strains lacking detectable carbapenemase genes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction. Carbapenemase-producing Enterobacterales (CPE) pose a clinical concern due to limited treatment options and plasmid-mediated spread of carbapenemase genes. The modified carbapenem inactivation method (mCIM) is increasingly used in clinical settings to detect CPE.
Gap Statement. Interpretation of mCIM results for isolates with reduced carbapenem susceptibility remains challenging.
Aim. To assess the interpretation of positive mCIM results in Klebsiella oxytoca isolates lacking detectable carbapenemase genes and exhibiting reduced carbapenem susceptibility and to propose a phenotypic testing strategy for accurate evaluation.
Methodology. Antimicrobial susceptibility testing with clavulanic or dipicolinic acid supplementation, phenotypic carbapenemase assays, carbapenem hydrolysis assays and whole-genome sequencing (WGS) were conducted on K. oxytoca strains.
Results. K. oxytoca strains were isolated from both blood and urine samples of a patient in a Japanese hospital. Although classified as susceptible by clinical breakpoints, these isolates exhibited reduced susceptibility to carbapenems. Although these strains were mCIM-positive, the zinc-supplemented carbapenem inactivation method did not support the presence of metallo-β-lactamase (MBL) activity. MIC reductions in the presence of CVA were consistent with inhibition of a class A β-lactamase. In contrast, dipicolinic acid supplementation did not reduce the meropenem MIC, ruling out MBL production. Furthermore, WGS revealed that both K. oxytoca strains lacked known carbapenemase genes, with blaOXY-2-4 being the only identifiable β-lactamase gene encoding a class A enzyme. No novel β-lactamase genes were identified; however, an enhanced blaOXY-2-4 expression-associated point mutation was found in the promoter region. Both K. oxytoca strains exhibited carbapenem-hydrolysing activity, although to a lesser extent than that of the MBL-producing strain.
Conclusion. We identified K. oxytoca strains that lacked known carbapenemase genes but that yielded positive mCIM results, possibly due to OXY-2 overproduction. Our study findings emphasize the need for cautious mCIM result interpretation for K. oxytoca and highlight the diagnostic value of combined susceptibility testing with clavulanic and dipicolinic acids to distinguish the underlying resistance mechanisms. Combining complementary clinical laboratory tests will enable clarification of the factors underlying mCIM positivity and guide clinical decision-making. en-copyright= kn-copyright= en-aut-name=TeraguchiHiroshi en-aut-sei=Teraguchi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OdaAyaka en-aut-sei=Oda en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WakaiSatoyo en-aut-sei=Wakai en-aut-mei=Satoyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawakamiSayoko en-aut-sei=Kawakami en-aut-mei=Sayoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaKoki en-aut-sei=Yoshida en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HayashiWataru en-aut-sei=Hayashi en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KitamuraNorikazu en-aut-sei=Kitamura en-aut-mei=Norikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= en-aut-name=SugaiMotoyuki en-aut-sei=Sugai en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YaharaKoji en-aut-sei=Yahara en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HirabayashiAki en-aut-sei=Hirabayashi en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Clinical Laboratory, Kindai University Nara Hospital kn-affil= affil-num=2 en-affil=Dental School, Okayama University 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=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=5 en-affil=Department of Clinical Laboratory, Kindai University Nara Hospital kn-affil= affil-num=6 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=7 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=8 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=9 en-affil=Dental School, Okayama University 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=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= en-keyword=blaOXY-2 kn-keyword=blaOXY-2 en-keyword=clavulanic acid kn-keyword=clavulanic acid en-keyword=Klebsiella oxytoca kn-keyword=Klebsiella oxytoca en-keyword=MIC kn-keyword=MIC en-keyword=modified carbapenem inactivation method kn-keyword=modified carbapenem inactivation method END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=3 article-no= start-page=405 end-page=421 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Practical Guidelines for Asthma Management (PGAM): Digest edition en-subtitle= kn-subtitle= en-abstract= kn-abstract=The international and national guidelines for asthma management are typically comprehensive and designed for respiratory specialists, making them less practical for primary care physicians who handle most asthma cases. Recognizing the need for more accessible guidelines, the Japan Asthma Society developed the Practical Guidelines for Asthma Management (PGAM). PGAM aims to provide a concise summary of key asthma management principles, increasing awareness, education, and support among nonspecialists and patients alike. It includes user-friendly tables and lists outlining common symptoms, triggers, diagnostic criteria, and basic management strategies, along with frequently encountered treatable traits and comorbidities. These elements are presented through simple, clinically relevant algorithms. A notable feature of PGAM is the “Basic Roadmap for Asthma Management,” which outlines a clear sequence for patient assessment, diagnosis, and treatment from initial consultation onward, offering an easy-to-follow visual guide. Additionally, the guidelines include methods for assessing airway inflammation, enabling patient phenotyping and endotyping. This supports a personalized treatment approach, particularly with biologics, aimed at achieving clinical remission. en-copyright= kn-copyright= en-aut-name=TamaokiJun en-aut-sei=Tamaoki en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaseHiroyuki en-aut-sei=Nagase en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=5 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=6 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=7 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=8 ORCID= en-aut-name=HoriguchiTakahiko en-aut-sei=Horiguchi en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TagayaEtsuko en-aut-sei=Tagaya en-aut-mei=Etsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AkabaTomohiro en-aut-sei=Akaba en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, Tokyo Women's Medical University kn-affil= affil-num=2 en-affil=Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School 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 Pulmonology, Yokohama City University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine 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 Medicine, Division of Allergology and Respiratory Medicine, School of Medicine, Showa University kn-affil= affil-num=8 en-affil=Department of Medicine, Division of Allergology and Respiratory Medicine, School of Medicine, Showa University kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Toyota Regional Medical Center kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Tokyo Women's Medical University kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Tokyo Women's Medical University kn-affil= affil-num=12 en-affil=Kindai University Hospital kn-affil= en-keyword=Asthma kn-keyword=Asthma en-keyword=Clinical remission kn-keyword=Clinical remission en-keyword=Management guidelines kn-keyword=Management guidelines en-keyword=Treatment algorithm kn-keyword=Treatment algorithm en-keyword=Practical tool kn-keyword=Practical tool 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=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=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=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=37 cd-vols= no-issue=5 article-no= start-page=e96 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=Examining the relationship between cesarean section scar and endometrial cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: The incidence of endometrial cancer (EC) has been increasing annually. Studies have reported that cesarean section (CS) is associated with a higher risk of developing EC than vaginal delivery (VD). However, few studies have examined the relationship between CS and EC development.
Methods: Data were extracted from the medical records of patients with EC and a history of childbirth who underwent EC treatment at 3 institutions. Factors contributing to EC development were analyzed between April 2010 and December 2024.
Results: Among patients EC and a history of childbirth, 8.7% (69/794) had undergone CS, and 50.7% (35/69) developed a CS scar. Compared with patients who had a VD or those without a CS scar, patients with a CS scar showed significantly shorter intervals from delivery to EC onset (VD: p=0.013; non-CS scar: p=0.031). A narrower residual myometrial thickness/adjacent myometrial thickness (RMT/AMT) ratio of the CS scar was significantly associated with a shorter interval from the last delivery to EC onset (p=0.034) and was independently associated with earlier EC onset after the last delivery in both univariate and multivariate analyses (p<0.001 and p=0.030, respectively).
Conclusion: A narrower RMT/AMT ratio in the CS scar was considerably associated with a shorter interval from the last delivery to EC onset. en-copyright= kn-copyright= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TaniYoshinori en-aut-sei=Tani en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItouHironori en-aut-sei=Itou en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShimizuMiyuki en-aut-sei=Shimizu en-aut-mei=Miyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DaoThi Hai Ly en-aut-sei=Dao en-aut-mei=Thi Hai Ly kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakatoHikari en-aut-sei=Nakato en-aut-mei=Hikari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkamotoKazuhiro en-aut-sei=Okamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Kagawa Rosai Hospital 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= en-keyword=Endometrial Cancer kn-keyword=Endometrial Cancer en-keyword=Cesarean Section kn-keyword=Cesarean Section en-keyword=Cesarean Section Scar kn-keyword=Cesarean Section Scar en-keyword=Interval from Delivery to Endometrial Cancer Onset kn-keyword=Interval from Delivery to Endometrial Cancer Onset en-keyword=Residual Myometrial Thicknes/Adjacent Myometrial Thickness Ratio kn-keyword=Residual Myometrial Thicknes/Adjacent Myometrial Thickness Ratio END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=10 article-no= start-page=489 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=Efficacy and Safety of Switching from Nalfurafine to Difelikefalin in Hemodialysis Patients with Refractory Pruritus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Hemodialysis-associated pruritus is common and can substantially impair quality of life. Given its heterogeneous pathophysiology and variable treatment response, individualized therapeutic strategies are needed. This study investigated the prevalence and severity of pruritus and clinical outcomes after switching from nalfurafine to difelikefalin. Methods: Clinical data from 108 maintenance hemodialysis patients whose pruritus severity was assessed using the Numerical Rating Scale (NRS) were retrospectively reviewed. Ten patients with persistent moderate-to-severe pruritus (NRS ≥ 3) despite treatment with nalfurafine were switched to difelikefalin in routine clinical practice, of whom eight completed the 16-week follow-up and were included in the switch group. Eight patients matched for age, sex, dialysis vintage, and baseline NRS served as controls. Changes in NRS scores at weeks 4 and 16, as well as adverse events, were evaluated. Results: Among 108 patients, 21 (20%) had no pruritus, while 20 (18.5%), 47 (43.5%), and 20 (18.5%) had mild, moderate, and severe pruritus, respectively. Of 14 patients receiving nalfurafine, 13 (92.9%) had persistent moderate-to-severe pruritus. In the switch group, mean NRS decreased from 5.9 ± 1.7 at baseline to 2.3 ± 2.3 at week 4 and 2.0 ± 0.9 at week 16 (p = 0.0156 and p = 0.0078, respectively), with no meaningful change in controls. No serious adverse events strongly related to difelikefalin were identified. Conclusions: Pruritus was highly prevalent in this cohort. Switching to difelikefalin was associated with rapid and sustained improvement in patients inadequately responsive to nalfurafine, with favorable tolerability, supporting its potential role as an individualized treatment option. 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=TokunagaKumiko en-aut-sei=Tokunaga en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OgisoYuko en-aut-sei=Ogiso en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MotoieMiwako en-aut-sei=Motoie en-aut-mei=Miwako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshitakeMegumi en-aut-sei=Yoshitake en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugimotoTaro en-aut-sei=Sugimoto en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Sugimoto Clinic kn-affil= affil-num=4 en-affil=Sugimoto Clinic kn-affil= affil-num=5 en-affil=Sugimoto Clinic kn-affil= affil-num=6 en-affil=Sugimoto Clinic kn-affil= affil-num=7 en-affil=Sugimoto Clinic kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=hemodialysis-associated pruritus kn-keyword=hemodialysis-associated pruritus en-keyword=difelikefalin kn-keyword=difelikefalin en-keyword=kappa-opioid receptor agonist kn-keyword=kappa-opioid receptor agonist en-keyword=refractory pruritus kn-keyword=refractory pruritus en-keyword=nalfurafine kn-keyword=nalfurafine 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=20260623 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-term association between the COVID-19 pandemic and language development at 3 years of age en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Few studies have examined the long-term association between the COVID-19 pandemic and language development in preschoolers or its effect modifiers. We therefore examined this association during health checkups of 3-year-olds in Japan.
Methods: This repeated cross-sectional study included 40,898 3-year-olds who underwent checkups in Okayama City, Japan. We compared children examined before (2017–2019) and during the pandemic (2020–2023). The primary outcome was physician-determined risk of language difficulties. The secondary outcome was children’s infrequent questions using words such as “what,” “who,” and “where.” Modified Poisson regression estimated RRs adjusted for confounders. Subgroup analyses examined effect modification by sex, childcare setting, and family size.
Results: The COVID-19 pandemic was associated with increased risk of language difficulties (RR 1.52, 95% CI 1.35–1.72). The association peaked in fiscal year 2021 and remained elevated throughout the pandemic. Secondary outcome showed elevated risk (RR 1.16, 95% CI 1.05–1.29). Girls and home-care children showed higher RRs than boys and preschool attendees.
Conclusions: The COVID-19 pandemic was associated with risk of language difficulties among 3-year-old children, with associations varying by sex and childcare setting. These findings suggest the importance of maintaining social interaction opportunities for young children during public health crises. en-copyright= kn-copyright= en-aut-name=MatsuoRumi en-aut-sei=Matsuo en-aut-mei=Rumi 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=NakamuraKazue en-aut-sei=Nakamura en-aut-mei=Kazue 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=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, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= 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=21 cd-vols= no-issue=3 article-no= start-page=e0344384 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Incidence of pelvic fractures after definitive radiotherapy for cervical cancer: A retrospective multicenter cohort study (The IPFAR study) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective
This multicenter study aimed to identify the risk factors for pelvic insufficiency fractures (PIFs) in women who received definitive radiotherapy (RT) as the initial treatment for cervical cancer and to examine the differences in the incidence of PIFs across institutions.
Patients and Methods The medical records of 208 women were reviewed. These women received definitive RT as an initial treatment for cervical cancer at four institutions between January 2016 and December 2018.
Results
The median age was 61.5 years (range: 29–93 years). Overall, 59 patients (28.4%) developed PIF, with 48 (81.4%) of them developing it within two years after completion of RT. Multivariate analysis identified postmenopausal status and treating institution as independent risk factors. The incidence of PIF varied significantly among institutions, ranging from 18.9% to 50.0%, despite no significant differences in patient demographics or RT protocols.
Conclusion
Substantial inter-institutional variation in PIF incidence was observed, even under standardized treatment conditions. These findings underscore the need for individualized risk assessment and institutional quality control in the long-term management of cervical cancer survivors. 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=YoshioKotaro en-aut-sei=Yoshio en-aut-mei=Kotaro 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=ImafukuNoriaki en-aut-sei=Imafuku en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoDan en-aut-sei=Yamamoto en-aut-mei=Dan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YorimitsuMasae en-aut-sei=Yorimitsu en-aut-mei=Masae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KodamaJunichi en-aut-sei=Kodama en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagasakaHisako en-aut-sei=Nagasaka en-aut-mei=Hisako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakanishiYoshie en-aut-sei=Nakanishi en-aut-mei=Yoshie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, 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 Radiology, Okayama University kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Okayama University kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Fukuyama Medical Center kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Fukuyama Medical Center kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Okayama University kn-affil= 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 µg/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=49 cd-vols= no-issue=8 article-no= start-page=1285 end-page=1290 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260825 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Adjusted Creatinine Clearance on Carboplatin Dosing in Endometrial Cancer: A Retrospective Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Carboplatin (CBDCA) dosing is commonly determined using the Calvert formula, with creatinine clearance (Ccr) estimated by the Cockcroft–Gault formula. In Japan, where serum creatinine (sCr) is usually measured enzymatically, unadjusted Ccr may overestimate glomerular filtration rate and lead to CBDCA overdosing. We retrospectively compared treatment exposure, hematologic toxicity, and exploratory oncologic outcomes in patients with endometrial cancer who received postoperative paclitaxel plus CBDCA therapy. Patients were grouped according to whether CBDCA dosing was based on the conventional Cockcroft–Gault formula (CG group) or on adjusted Ccr calculated by adding 0.2 mg/dL to sCr (adjusted group). The incidence of Grade ≥3 neutropenia was significantly lower in the adjusted group than in the CG group. The 5-year progression-free survival (PFS) rate was numerically lower in the adjusted group than in the CG group, although no statistically significant difference was observed between the groups. Because the number of PFS events was limited, the effect of adjusted Ccr-based dosing on oncologic outcomes remains uncertain. These findings suggest that adjusted Ccr-based dosing may reduce hematologic toxicity in routine clinical practice. However, given the limited number of PFS events and the wide uncertainty in survival estimates, further studies are needed to clarify its impact on oncologic outcomes. en-copyright= kn-copyright= en-aut-name=KatayamaKentaro en-aut-sei=Katayama en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ImamuraMakio en-aut-sei=Imamura en-aut-mei=Makio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UeharaTakashi en-aut-sei=Uehara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Clinical Support, Kurashiki Medical Center kn-affil= affil-num=3 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=carboplatin kn-keyword=carboplatin en-keyword=creatinine clearance kn-keyword=creatinine clearance en-keyword=dose adjustment kn-keyword=dose adjustment en-keyword=endometrial cancer kn-keyword=endometrial cancer en-keyword=neutropenia kn-keyword=neutropenia en-keyword=pharmaceutical care kn-keyword=pharmaceutical care 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 Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne Université kn-affil= affil-num=3 en-affil=Laboratoire Magmas et Volcans, Université Clermont-Auvergne kn-affil= affil-num=4 en-affil=UMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne Université 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 Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne Université 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 Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne Université 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=10 cd-vols= no-issue=3 article-no= start-page=e202500335 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=Substitution‐Dependent Modulation of Photophysical Properties of 2,7‐ and 3,6‐Dinaphthyl‐9‐phenylcarbazoles in Solution and Solid State en-subtitle= kn-subtitle= en-abstract= kn-abstract=The photophysical properties of two positional isomers of dinaphthyl-9-phenylcarbazoles (2,7-DNpPCz and 3,6-DNpPCz) were systematically investigated in solution and solid states. Experimental measurements revealed a pronounced positional dependence, although both compounds exhibit fluorescence in solution and the solid state. On average, the 2,7-isomers exhibit larger fluorescence rate values than the 3,6-isomers, although the magnitude of this difference varies among individual compounds. To gain mechanistic insight, density function theory (DFT) and time-dependence DFT calculations were performed at the (TD)-B3LYP/6-31+G(d) level. The results show that 2,7-DNpPCz derivatives possess delocalized frontier orbitals and large oscillator strengths for the S1 ← S0 transition, whereas 3,6-DNpPCz derivatives exhibit smaller oscillator strengths with mixed orbital contributions, leading to weaker transition probabilities. These combined findings demonstrate that substitution geometry critically governs radiative decay dynamics in carbazole-based luminophores and provide valuable guidelines for the molecular design of efficient solid-state 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=MoriTadashi en-aut-sei=Mori en-aut-mei=Tadashi 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=Research Center for Environmental Preservation and Graduate School of Engineering, The University of Osaka kn-affil= affil-num=3 en-affil=Department of Chemistry, Faculty of Environment, Life, Natural Sciences and Technology, Okayama University kn-affil= en-keyword=carbazole kn-keyword=carbazole en-keyword=emission lifetime kn-keyword=emission lifetime en-keyword=emission quantum yield kn-keyword=emission quantum yield en-keyword=photoluminescence kn-keyword=photoluminescence en-keyword=solid-state emission kn-keyword=solid-state emission 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 Å 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=28 cd-vols= no-issue=3 article-no= start-page=e70062 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=Sexual Dimorphism in Vertebral Number: Developmental Implications Inferred From Vertebral and Body Proportions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Segmentation is a fundamental feature of vertebrate body plans, and variation in vertebral number contributes substantially to morphological diversity. Although sexual dimorphism in vertebral number has been documented in several vertebrate lineages, its developmental basis remains poorly understood. Here, we report pronounced sexual dimorphism in vertebral number in the western Indian endemic ricefish Oryzias setnai, distributed across ~1800 km. Radiographic analyses of individuals collected throughout its range revealed that vertebral number increased with latitude in both sexes, while males consistently possessed more vertebrae than females irrespective of geographic origin. Size-adjusted analyses showed that this dimorphism is associated with sex differences in head size and position-dependent variation in vertebral length. However, positional allometric analyses demonstrated that both the magnitude and direction of these sex differences vary markedly during growth. In particular, among smaller individuals, posterior vertebrae were relatively shorter in males than in females, suggesting reduced somite length in the posterior body axis of male embryos and potentially reflecting sex-specific differences in the dynamics of somitogenesis. Given that this variation arises between males and females within a single species sharing an essentially identical genetic background, O. setnai provides a rare empirical system not only for linking early developmental processes to intraspecific sexual variation in vertebrate body plans but also as a powerful model to investigate the developmental basis of body plan variation across species. en-copyright= kn-copyright= en-aut-name=YamahiraKazunori en-aut-sei=Yamahira en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AnoopV. K. en-aut-sei=Anoop en-aut-mei=V. K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RaghavanRajeev en-aut-sei=Raghavan en-aut-mei=Rajeev kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaYoshitaka en-aut-sei=Tanaka en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= affil-num=1 en-affil=Tropical Biosphere Research Center, University of the Ryukyus kn-affil= affil-num=2 en-affil=Tropical Biosphere Research Center, University of the Ryukyus kn-affil= affil-num=3 en-affil=Department of Fisheries Resource Management, Kerala University of Fisheries and Ocean Studies kn-affil= affil-num=4 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=5 en-affil=Ushimado Marine Institute, Okayama University kn-affil= en-keyword=axial patterning kn-keyword=axial patterning en-keyword=developmental mechanisms kn-keyword=developmental mechanisms en-keyword=latitude kn-keyword=latitude en-keyword=Oryzias kn-keyword=Oryzias en-keyword=segmentation interval kn-keyword=segmentation interval en-keyword=vertebral length kn-keyword=vertebral length 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=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 Ōmura 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 Ōmura 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=Ōmura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=3 en-affil=Ōmura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=4 en-affil=Ōmura 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=Ōmura 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 Ōmura Natural Compound Library kn-keyword=the Ōmura Natural Compound Library en-keyword=antibacterial activity kn-keyword=antibacterial activity END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=3 article-no= start-page=110 end-page=112 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130301 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An Efficient Synthesis of Limipterin [2'-O-(2-Acetamido-2-deoxy-β- D-glucopyranosyl) -L- biopterin] via N2 - (N ,N -Dimethylamino )-methylene- 3-[2-(4-nitrophenyl)ethyl]-L-biopterin en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YamamotoHiroshi en-aut-sei=Yamamoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HanayaTadashi en-aut-sei=Hanaya en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaKoichiro en-aut-sei=Harada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=PfleidererWolfgang en-aut-sei=Pfleiderer en-aut-mei=Wolfgang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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= affil-num=5 en-affil=Universitat Konstanz, Fakultat fur Chemie kn-affil= END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=3 article-no= start-page=100085 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=Effects of serotonin transporters on myocardial cell injury during ischemia/reperfusion in rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Serotonin (5-HT) reuptake in the heart is mediated by the platelet serotonin reuptake transporter (SERT) and the cardiomyocyte plasma membrane monoamine transporter (PMAT). However, the specific roles of these transporters in myocardial cell injury during ischemia/reperfusion remain unclear. Sprague-Dawley rats underwent left coronary artery occlusion followed by reperfusion. Using cardiac microdialysis technique, fluoxetine (SERT inhibitor, 900 μM) or decynium 22 (PMAT inhibitor, 100 μM) was administered locally to the ischemic region. Myoglobin concentrations in the dialysate were measured during ischemia followed by reperfusion. In the fluoxetine-treated group, peak myoglobin concentration (14,889 ± 1364 ng/mL) during 0–15 min of reperfusion was significantly higher compared to both the control group (9800 ± 1627 ng/mL) and the decynium 22-treated group (8172 ± 877 ng/mL) (P < 0.01 for both). Local SERT inhibition exacerbated myocardial cell injury during ischemia/reperfusion. However, co-inhibition of PMAT reduced myocardial cell injury under SERT inhibition to the control level. en-copyright= kn-copyright= en-aut-name=KishiYoshimasa en-aut-sei=Kishi en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimizuShuji en-aut-sei=Shimizu en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurokoYosuke en-aut-sei=Kuroko en-aut-mei=Yosuke 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=AkiyamaTsuyoshi en-aut-sei=Akiyama en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Cardiac Physiology, National Cerebral and Cardiovascular Center kn-affil= affil-num=6 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= en-keyword=Myocardial ischemia/reperfusion injury kn-keyword=Myocardial ischemia/reperfusion injury en-keyword=Platelets kn-keyword=Platelets en-keyword=Serotonin reuptake kn-keyword=Serotonin reuptake en-keyword=Cardiac microdialysis kn-keyword=Cardiac microdialysis en-keyword=Myoglobin kn-keyword=Myoglobin 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=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=53 cd-vols= no-issue=13 article-no= start-page=e2025GL120078 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=Limits of Water Storage in Stishovite at Deep Mantle Conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=The deep Earth water cycle is a key process in Earth's evolution. Stishovite has been proposed as a major carrier of water from the surface into the lower mantle. However, its role remains unclear because its water solubility is controversial. We investigated the water solubility of Al-free stishovite at pressures of 33–38 GPa and temperatures of 700–1200 K using in situ X-ray diffraction in an advanced multianvil apparatus. Water solubility is high, around 3 wt%, at 700 K but decreases rapidly with increasing temperature and becomes negligible (<1,000 ppm), at temperatures above 1000 K. These results suggest that pure stishovite is unlikely to transport significant amounts of water into Earth's lower mantle under comparable pressure-temperature conditions. Previously reported high water contents in pure stishovite under deep Earth conditions likely reflect the solubility of post-stishovite or experimental artifacts. en-copyright= kn-copyright= en-aut-name=WangFei en-aut-sei=Wang en-aut-mei=Fei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChanyshevArtem en-aut-sei=Chanyshev en-aut-mei=Artem kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ManLianjie en-aut-sei=Man en-aut-mei=Lianjie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SongYunke en-aut-sei=Song en-aut-mei=Yunke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangLin en-aut-sei=Wang en-aut-mei=Lin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=TsujinoNoriyoshi en-aut-sei=Tsujino en-aut-mei=Noriyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BhatShrikant en-aut-sei=Bhat en-aut-mei=Shrikant kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FarlaRobert en-aut-sei=Farla en-aut-mei=Robert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatsuraTomoo en-aut-sei=Katsura en-aut-mei=Tomoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=2 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=3 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=4 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=5 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=6 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=7 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=8 en-affil=Deutsches Elektronen‐Synchrotron DESY kn-affil= affil-num=9 en-affil=Deutsches Elektronen‐Synchrotron DESY kn-affil= affil-num=10 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= en-keyword=stishovite kn-keyword=stishovite en-keyword=high pressure kn-keyword=high pressure en-keyword=deep mantle kn-keyword=deep mantle en-keyword=multianvil press kn-keyword=multianvil press en-keyword=water cycle kn-keyword=water cycle 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=61 cd-vols= no-issue=4 article-no= start-page=720 end-page=738 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260320 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The effects of pressure on immiscibility in metallic, core‐forming liquids: Implications for protoplanetary differentiation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mechanisms for metal core formation in rocky planetesimals and planetary embryos remain poorly constrained, in part due to complexities arising from immiscibility in core-forming liquids at low pressures. To assess the pressure dependence of immiscibility and its role in protoplanetary differentiation, we performed experiments at 3 and 5 GPa in the system Fe0.9Ni0.1 + S, P, C. Immiscibility arises due to the highly non-ideal nature of light element mixing in Fe liquids, and results in separation of Fe-rich (S-depleted, C-rich, P-rich) and FeS-rich (S-rich, C-rich, P-depleted) liquids. For a broad range of core-forming liquid compositions, a miscibility gap is only present at pressures <5 GPa. With increasing pressure, the behavior of complex systems converges on that of the Fe-S-C ternary, although S-P-C interactions continue to influence metal liquid compositions and stability. Comparison with planetary core compositions derived from meteorite data suggests that immiscibility can play a significant role during melting in planetesimals, and up to medium-sized planetary embryos. In turn, the importance of immiscibility during differentiation depends on the extent of melting, mechanisms for core formation, and corollary degree of light element loss from planetary bodies. en-copyright= kn-copyright= en-aut-name=BromileyGeoffrey David en-aut-sei=Bromiley en-aut-mei=Geoffrey David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TerasakiHidenori en-aut-sei=Terasaki en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=VarnamMatthew en-aut-sei=Varnam en-aut-mei=Matthew kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=School of GeoSciences, University of Edinburgh, Grant Institute kn-affil= affil-num=2 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=3 en-affil=School of GeoSciences, University of Edinburgh, Grant Institute kn-affil= 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=14 cd-vols= no-issue= article-no= start-page=100628 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=Clinical phenotypes and the risk factors of mild pulmonary hypertension en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The definition of pulmonary hypertension (PH) was revised as mean pulmonary arterial pressure (mPAP) >20 mmHg from ≥25 mmHg in the recent PH guidelines; however, the characteristics of PH patients with mPAP 21–24 mmHg have not been well described.
Methods: A total of 1080 individuals who underwent right heart catheterization (2018–2022) was categorized into 3 groups by mPAP: no PH with mPAP ≤20 mmHg, mild PH with mPAP 21–24 mmHg, and conventional PH with mPAP ≥25 mmHg. We assessed PH subtypes of hemodynamic and clinical classification and compared survival outcomes (all-cause mortality, heart failure hospitalization, lung transplant) using Cox models.
Results: Of them, 391 patients (36.2%) were diagnosed as PH including mild PH (n = 137) and conventional PH (n = 254). Phenotypically, mild PH was predominantly characterized by pre-capillary hemodynamics and Group 2 clinical classification. Mild PH is associated with an intermediate prognosis: outcomes are more favorable than in conventional PH but inferior to no PH (HR 1.74 [95% CI 1.15–2.61]). While the two PH phenotypes appear to share comorbidity-related factors, hemodynamic parameters were associated with survival outcomes not in mild PH but in conventional PH.
Conclusions: The observation that mild PH constitutes approximately one-third of overall PH cases carries substantial clinical weight. The newly identified mild PH cohort was characterized mainly by pre-capillary and Group 2 subtypes. While mild PH is associated with an intermediate prognosis, comorbidities appear to be the primary determinant of outcomes in this group, unlike in conventional PH where hemodynamics play a larger role. en-copyright= kn-copyright= en-aut-name=TayaSatoshi en-aut-sei=Taya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukudaYoshitake en-aut-sei=Fukuda en-aut-mei=Yoshitake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanezawaMisaki en-aut-sei=Kanezawa en-aut-mei=Misaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakayaYoichi en-aut-sei=Takaya en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=mild pulmonary hypertension kn-keyword=mild pulmonary hypertension en-keyword=prognosis kn-keyword=prognosis en-keyword=risk factor kn-keyword=risk factor END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=5 article-no= start-page=e70502 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260420 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=UNC45B Reduction With Aging: A Myofiber-Intrinsic Promoting Factor for Sarcopenia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Skeletal muscle mass and force decline with age, and the loss of muscle force precedes muscle atrophy. However, the underlying mechanisms remain unclear. Here, we investigated the role of the myosin co-chaperone, uncoordinated mutant number-45 myosin chaperone B (UNC45B), in regulating muscle mass and force. UNC45B expression decreased in mouse gastrocnemius muscle with age, particularly at 24 months old, and adeno-associated virus vector-mediated knockdown of Unc45b in 3-month-old mouse triceps surae muscle first reduced plantar flexor torque and then decreased gastrocnemius muscle mass. In addition, Unc45b knockdown in the triceps surae muscle resulted in lower bone mineral density. While maximum Ca2+-activated force in mechanically skinned fibers was not affected by Unc45b knockdown, Unc45b knockdown decreased the ratio of depolarization-induced force to the maximum Ca2+-activated force. We established tamoxifen-inducible skeletal muscle-specific Unc45b knockout (Unc45b imKO) mice to investigate whether the muscle atrophy and weakness due to the loss of Unc45b impacts metabolism and behavior. We found that Unc45b imKO reduced muscle mass and force at a whole-body level, but did not influence systemic glucose tolerance, insulin sensitivity, or the respiratory exchange ratio. However, Unc45b imKO mice reduced the amount of deeper non-rapid eye movement sleep, locomotor activity, and body temperature during the sleep phase. We conclude that UNC45B is essential for maintaining fast-twitch muscle mass and muscle force. In addition, Unc45b deficiency-mediated muscle loss is also associated with bone fragility, decreased body temperature, and impaired sleep quality. en-copyright= kn-copyright= en-aut-name=MishimaTaiga en-aut-sei=Mishima en-aut-mei=Taiga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagamuneTaiga en-aut-sei=Nagamune en-aut-mei=Taiga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TadaSaori en-aut-sei=Tada en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeDaiki en-aut-sei=Watanabe en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TokudaNao en-aut-sei=Tokuda en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamadaTakashi en-aut-sei=Yamada en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Hashimoto‐HachiyaAkiko en-aut-sei=Hashimoto‐Hachiya en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Higo‐YamamotoSayaka en-aut-sei=Higo‐Yamamoto en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KidoKohei en-aut-sei=Kido en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IkedoAoi en-aut-sei=Ikedo en-aut-mei=Aoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ImaiYuuki en-aut-sei=Imai en-aut-mei=Yuuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujitaRyo en-aut-sei=Fujita en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MizunoSeiya en-aut-sei=Mizuno en-aut-mei=Seiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakahashiSatoru en-aut-sei=Takahashi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OishiKatsutaka en-aut-sei=Oishi en-aut-mei=Katsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AtoSatoru en-aut-sei=Ato en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OgasawaraRiki en-aut-sei=Ogasawara en-aut-mei=Riki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=2 en-affil=Department of Life Science and Applied Chemistry, Nagoya Institute of Technology kn-affil= affil-num=3 en-affil=Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=4 en-affil=Graduate School of Sport and Health Sciences, Osaka University of Health and Sport Sciences kn-affil= affil-num=5 en-affil=Graduate School of Health Sciences, Sapporo Medical University kn-affil= affil-num=6 en-affil=Graduate School of Health Sciences, Sapporo Medical University kn-affil= affil-num=7 en-affil=Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=8 en-affil=Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=9 en-affil=Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=10 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University kn-affil= affil-num=11 en-affil=Division of Integrative Pathophysiology, Proteo‐Science Center, PIAS, Ehime University kn-affil= affil-num=12 en-affil=Division of Integrative Pathophysiology, Proteo‐Science Center, PIAS, Ehime University kn-affil= affil-num=13 en-affil=Division of Regenerative Medicine, Transborder Medical Research Center, Institute of Medicine, University of Tsukuba kn-affil= affil-num=14 en-affil=Laboratory Animal Resource Center in Transborder Medical Research Center, Institute of Medicine, University of Tsukuba kn-affil= affil-num=15 en-affil=Laboratory Animal Resource Center in Transborder Medical Research Center, Institute of Medicine, University of Tsukuba kn-affil= affil-num=16 en-affil=Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=17 en-affil=Faculty of Medical Science, Nippon Sport Science University kn-affil= affil-num=18 en-affil=Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= en-keyword=chaperone kn-keyword=chaperone en-keyword=muscle atrophy kn-keyword=muscle atrophy en-keyword=muscle force kn-keyword=muscle force en-keyword=sarcopenia kn-keyword=sarcopenia 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=137 cd-vols= no-issue= article-no= start-page=103183 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=Activation phosphorylation and dephosphorylation dynamics of Ca2+/Calmodulin-dependent protein kinase Iα in HeLa cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ca²⁺/calmodulin-dependent protein kinase I (CaMKI), a multifunctional CaM-activated protein kinase, is involved in various Ca²⁺ signaling pathways including neuronal development. Here, we characterize the phosphorylation at Thr177 (an activation Thr residue) and subsequent dephosphorylation dynamics of CaMKIα in HeLa cells upon physiological stimulation that elevates intracellular Ca²⁺. ATP induced CaMKIα phosphorylation within 5–10 min; phosphorylation was then blocked by CaMKK inhibitor TIM-063, or by the depletion of extracellular Ca²⁺. This was followed by gradual dephosphorylation to basal levels within 30–60 min. Histamine induced CaMKIα phosphorylation, peaking within 3–4 min; this process was abolished by treatment with either TIM-063 or intracellular Ca²⁺ chelation using BAPTA-AM and thapsigargin; however, not by extracellular Ca²⁺ depletion. CaMKIα was then rapidly dephosphorylated to basal levels within 10 min. Consistently, histamine-induced (but not ATP-induced) CaMKIα phosphorylation was absent in triple IP₃ receptor-knockout HeLa cells. Dephosphorylation of CaMKIα after ATP-induced phosphorylation was unaffected by okadaic acid or CaMK phosphatase (CaMKP, known as PPM1F) inhibitors (ANS and ANDS). We found that HeLa cell extracts contained Mg2+/Mn2+-dependent CaMKIα dephosphorylation activity that was insensitive to ANS and ANDS. Furthermore, co-expression of PP2Cα fully abolished ATP-, histamine-, or ionomycin-stimulated CaMKIα phosphorylation, which is consistent with in vitro dephosphorylation of CaMKIα at Thr177 by recombinant PP2Cα. Taken together, these results reveal that agonist-induced Ca²⁺ influx from the extracellular space or release from intracellular stores transiently activates CaMKK-CaMKIα signaling in HeLa cells, which is shut off by dephosphorylation catalyzed by PP2Cα as a promising candidate for CaMKIα phosphatase. en-copyright= kn-copyright= en-aut-name=ChenYerun en-aut-sei=Chen en-aut-mei=Yerun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MikiMasao en-aut-sei=Miki en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MagariMasaki en-aut-sei=Magari en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OhtsukaSatomi en-aut-sei=Ohtsuka en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EtoMasumi en-aut-sei=Eto en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshidaAtsuhiko en-aut-sei=Ishida en-aut-mei=Atsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuizuFutoshi en-aut-sei=Suizu en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MizutaniAkihiro en-aut-sei=Mizutani en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AndoHideaki en-aut-sei=Ando en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MikoshibaKatsuhiko en-aut-sei=Mikoshiba en-aut-mei=Katsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TokumitsuHiroshi en-aut-sei=Tokumitsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Veterinary Science, Okayama University of Science kn-affil= affil-num=6 en-affil=Laboratory of Molecular Brain Science, Graduate School of Integrated Sciences for Life, Hiroshima University kn-affil= affil-num=7 en-affil=Clinical Examination Department, Kagawa Prefectural University of Health Sciences kn-affil= affil-num=8 en-affil=Department of Pharmacotherapeutics, Showa Pharmaceutical University kn-affil= affil-num=9 en-affil=Laboratory for Developmental Neurobiology, RIKEN Center for Brain Science kn-affil= affil-num=10 en-affil=Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University kn-affil= affil-num=11 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=CaMKIα kn-keyword=CaMKIα en-keyword=CaMKK kn-keyword=CaMKK en-keyword=PP2Cα kn-keyword=PP2Cα en-keyword=Phosphorylation kn-keyword=Phosphorylation en-keyword=Dephosphorylation kn-keyword=Dephosphorylation en-keyword=Ca2+-signaling kn-keyword=Ca2+-signaling 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=192 cd-vols= no-issue= article-no= start-page=137 end-page=146 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=Deepening Students' Subject View Through Compulsory Subjects in Elementary Home Economics at the Faculty of Education, Okayama University: Based on the Results of the 2024-2025 Survey kn-title=岡山大学教育学部初等家庭科必修科目を通した学生の教科観の深化 ―2024-2025年度のアンケート調査の結果から― en-subtitle= kn-subtitle= en-abstract= kn-abstract=　本研究では，岡山大学教育学部新カリキュラムにおける，初等家庭科の必修科目「内容構成基礎」，「指導法基礎」，「指導法Ⅰ」の3科目を通して，履修学生の家庭科に対する教科観（イメージや考え方）がどのように変化したのかを，アンケート調査を用いて明らかにすることを目的とした。「指導する立場から小学校家庭科を学修して，家庭科のイメージや考え方が変化した」に対する5件法の回答では，「あてはまる」，「ややあてはまる」を合わせた肯定的な回答の割合は，「内容構成基礎」90.1%，「指導法基礎」88.5%，「指導法Ⅰ」95.0%と，「指導法基礎」でやや下がったものの，「指導法Ⅰ」で最も高い割合を示した。自由記述のテキスト分析では，必修科目の学修を通した学生の教科観は，「教科の学習内容の理解」→「教科理念の理解」→「教科指導の理解」の段階を踏むことにより，徐々に深化したと推察された。 en-copyright= kn-copyright= en-aut-name=MORIChiharu en-aut-sei=MORI en-aut-mei=Chiharu kn-aut-name=森千晴 kn-aut-sei=森 kn-aut-mei=千晴 aut-affil-num=1 ORCID= en-aut-name=HISANARIMiyuki en-aut-sei=HISANARI en-aut-mei=Miyuki kn-aut-name=久成三有紀 kn-aut-sei=久成 kn-aut-mei=三有紀 aut-affil-num=2 ORCID= en-aut-name=SHINOHARAYoko en-aut-sei=SHINOHARA en-aut-mei=Yoko kn-aut-name=篠原陽子 kn-aut-sei=篠原 kn-aut-mei=陽子 aut-affil-num=3 ORCID= en-aut-name=LEEKyoungwon en-aut-sei=LEE en-aut-mei=Kyoungwon kn-aut-name=李璟媛 kn-aut-sei=李 kn-aut-mei=璟媛 aut-affil-num=4 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 affil-num=2 en-affil=Faculty of Education, Okayama University kn-affil=岡山大学学術研究院教育学域 affil-num=3 en-affil=Faculty of Education, Okayama University kn-affil=岡山大学学術研究院教育学域 affil-num=4 en-affil=Faculty of Education, Okayama University kn-affil=岡山大学学術研究院教育学域 en-keyword=初等家庭科 kn-keyword=初等家庭科 en-keyword=教員養成 kn-keyword=教員養成 en-keyword=教科観 kn-keyword=教科観 en-keyword=教科内容 kn-keyword=教科内容 en-keyword=教科教育 kn-keyword=教科教育 END start-ver=1.4 cd-journal=joma no-vol=192 cd-vols= no-issue= article-no= start-page=13 end-page=26 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=Leadership Self-Efficacy through Collaborative Experiences in Group Activities: The Role of Habitual Reflection on Experience kn-title=集団活動での協働経験を通じて培われるリーダーシップ効力感 ― 経験を振り返る習慣がもつ意味 ― en-subtitle= kn-subtitle= en-abstract= kn-abstract=　本研究では，日常的な集団活動での協働経験および経験学習習慣が，リーダーシップ効力感とどのように関連するのかを検討した。大学生を対象に質問紙調査を実施し，99名の有効回答を分析対象とした。因子分析により，協働経験について「協働的問題解決」，「集団内責任遂行」，「意思決定参画」の3因子が抽出された。リーダーシップ効力感（鼓舞力，変革力，共感力）との関連を階層的重回帰分析で検討した結果，集団内責任遂行の経験は変革力と，意思決定参画の経験は鼓舞力と関連し，経験学習習慣は変革力および共感力と正の関連を示した。また，協働的問題解決の経験が少ない場合には，経験学習習慣が鼓舞力と変革力を補完的に高める可能性が示唆された。得られた知見に基づき，大学生のリーダーシップ育成における協働経験の内容に応じた支援と，経験を省察する習慣形成の重要性を議論した。 en-copyright= kn-copyright= en-aut-name=MISAWARyo en-aut-sei=MISAWA en-aut-mei=Ryo kn-aut-name=三沢良 kn-aut-sei=三沢 kn-aut-mei=良 aut-affil-num=1 ORCID= en-aut-name=KANEMIShunta en-aut-sei=KANEMI en-aut-mei=Shunta kn-aut-name=金見駿汰 kn-aut-sei=金見 kn-aut-mei=駿汰 aut-affil-num=2 ORCID= en-aut-name=HASEGAWANaoko en-aut-sei=HASEGAWA en-aut-mei=Naoko kn-aut-name=長谷川尚子 kn-aut-sei=長谷川 kn-aut-mei=尚子 aut-affil-num=3 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 affil-num=2 en-affil=Benesse Corporation kn-affil=株式会社ベネッセコーポレーション affil-num=3 en-affil=Faculty of Human Sciences, Department of Psychology, Bunkyo University kn-affil=文教大学人間科学部心理学科 en-keyword=集団活動 kn-keyword=集団活動 en-keyword=協働経験 kn-keyword=協働経験 en-keyword=リーダーシップ効力感 kn-keyword=リーダーシップ効力感 en-keyword=経験学習習慣 kn-keyword=経験学習習慣 en-keyword=大学生 kn-keyword=大学生 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=138 cd-vols= no-issue=2 article-no= start-page=40 end-page=44 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=Intestinal homeostasis and autoimmune arthritis mediated by type 3 immunity kn-title=３型免疫応答による腸管恒常性維持および自己免疫性関節炎誘導機構 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HirotaKeiji en-aut-sei=Hirota en-aut-mei=Keiji kn-aut-name=廣田圭司 kn-aut-sei=廣田 kn-aut-mei=圭司 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Immunology and Inflammation, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学学術研究院医歯薬学域　炎症免疫学 en-keyword=3型免疫 kn-keyword=3型免疫 en-keyword=炎症性サイトカイン kn-keyword=炎症性サイトカイン en-keyword=組織炎症 kn-keyword=組織炎症 en-keyword=Th17細胞 kn-keyword=Th17細胞 END start-ver=1.4 cd-journal=joma no-vol=138 cd-vols= no-issue=2 article-no= start-page=38 end-page=39 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 Cancer Research (2025 Hayashibara Prize and Yamada Prize) kn-title=令和７年度岡山医学会賞　がん研究奨励賞（林原賞・山田賞） en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=UmedaHibiki en-aut-sei=Umeda en-aut-mei=Hibiki kn-aut-name=梅田響 kn-aut-sei=梅田 kn-aut-mei=響 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, 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　消化器外科学 END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=6 article-no= start-page=979 end-page=988 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy of bepotastine compared with hydroxyzine in preventing rituximab-induced infusion-related reactions in non-hodgkin lymphoma patients: a phase II, double-blind, multicenter, and randomized trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background This study evaluated the efficacy of hydroxyzine and bepotastine, first- and second-generation H1 receptor antagonists (H1RA), as pretreatments to prevent infusion-related reactions (IRRs) during the initial rituximab infusion in patients with non-Hodgkin lymphoma.
Methods In this double-blind, multicenter, randomized phase II study, 40 patients received hydroxyzine or bepotastine with acetaminophen 30 min before rituximab infusion. Primary endpoint was incidence of ≥ grade 2 IRRs based on the National Cancer Institute Common Terminology Criteria for Adverse Events. Secondary endpoints included IRRs severity, time to IRR onset, and H1RA-induced drowsiness.
Results Incidence of ≥ grade 2 IRRs was 52.4% and 31.6% for the hydroxyzine (n = 21) and bepotastine (n = 19) groups, respectively (P = 0.184). Distribution of initial and maximum IRR grades in the two groups was not statistically significant (P = 0.846 and 0.555). Median time (range) to IRR onset in the two groups was 67 (12–112) and 62 (10–119) min, respectively (P = 0.981). Median visual analog scale score (range and 75th percentile) for drowsiness was 37 (0–100, 46) and 12 (0–100, 29) mm in the two groups, respectively (P = 0.138). Incidence of ≥ grade 2 IRRs in the absence of bone marrow infiltration was 43.8% and 14.3% in the two groups, respectively (P = 0.118), and no group differences were observed with bone marrow infiltration.
Conclusions Bepotastine did not show significant superiority over hydroxyzine in preventing rituximab-induced IRRs due to the small sample size. Nevertheless, this exploratory study provides insight for further confirmatory studies.
Trial registration number and date of registration jRCTs051220169; February 14, 2023. en-copyright= kn-copyright= en-aut-name=KitahiroYumi en-aut-sei=Kitahiro en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MinamiHironobu en-aut-sei=Minami en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=YakushijinKimikazu en-aut-sei=Yakushijin en-aut-mei=Kimikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurataKeiji en-aut-sei=Kurata en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakaiRina en-aut-sei=Sakai en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaekiMiki en-aut-sei=Saeki en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Okazoe-HirakawaYuri en-aut-sei=Okazoe-Hirakawa en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IidaKotaro en-aut-sei=Iida en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MuraseNatsuko en-aut-sei=Murase en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HarimaIsamu en-aut-sei=Harima en-aut-mei=Isamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KitamuraNaoko en-aut-sei=Kitamura en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=OmuraTomohiro en-aut-sei=Omura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SugimotoTakeshi en-aut-sei=Sugimoto en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakakuraHidetomo en-aut-sei=Takakura en-aut-mei=Hidetomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KitaoAkihito en-aut-sei=Kitao en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TakahashiMasako en-aut-sei=Takahashi en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShimoyamaManabu en-aut-sei=Shimoyama en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OkunoMamoru en-aut-sei=Okuno en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 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=21 ORCID= affil-num=1 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=2 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=5 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=6 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=7 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=8 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=9 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=10 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=11 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=13 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=14 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Kita-Harima Medical Center kn-affil= affil-num=16 en-affil=Department of Hematology and Oncology, Kita-Harima Medical Center kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Kita-Harima Medical Center kn-affil= affil-num=18 en-affil=Department of Pharmacy, Kita-Harima Medical Center kn-affil= affil-num=19 en-affil=Department of Hematology and Oncology, Kohnan Medical Center kn-affil= affil-num=20 en-affil=Department of Pharmacy, Kohnan Medical Center kn-affil= affil-num=21 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= en-keyword=Rituximab kn-keyword=Rituximab en-keyword=Infusion-related reactions kn-keyword=Infusion-related reactions en-keyword=Non-Hodgkin lymphoma kn-keyword=Non-Hodgkin lymphoma en-keyword=Bepotastine kn-keyword=Bepotastine en-keyword=Hydroxyzine kn-keyword=Hydroxyzine en-keyword=Drowsiness kn-keyword=Drowsiness 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= 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=58 cd-vols= no-issue=3 article-no= start-page=476 end-page=477 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful removal of a buried lumen-apposing metal stent without complications using pancreatic drainage and a hemostatic agent en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki 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 Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science 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=30 cd-vols= no-issue=3 article-no= start-page=e70025 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Polished Rice Regulates Maturation but Not Survival of Secondary Cells in Drosophila Male Accessory Gland en-subtitle= kn-subtitle= en-abstract= kn-abstract=In Drosophila males, the accessory gland is responsive to nutrient signal-dependent regulation of fertility/fecundity. The accessory gland is composed of two types of binucleated epithelial cells, about 1000 main cells and 60 secondary cells (SCs). The transcription factors Defective proventriculus (Dve), Abdominal-B, and Ecdysone receptors (EcRs) are strongly expressed in adult SCs. In response to nutrient conditions during development, coordinated action between Dve and ecdysone signaling determines the optimal number of SCs and regulates their maturation. A downstream effector of ecdysone signaling, Ftz-F1, is crucial in this process. Another downstream effector, Polished rice (Pri), is small peptides of 11 or 32 amino acids. Here we show that pri is required for maturation of SCs and for male fecundity, whereas it is not involved in determination of the number of SCs. We provide evidence that Pri acts downstream of Ftz-F1 to regulate maturation but not survival of SCs. en-copyright= kn-copyright= en-aut-name=OtsuneShinichi en-aut-sei=Otsune en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukaMirai en-aut-sei=Matsuka en-aut-mei=Mirai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShirakashiChisato en-aut-sei=Shirakashi en-aut-mei=Chisato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhangXuanshuo en-aut-sei=Zhang en-aut-mei=Xuanshuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakagoshiHideki en-aut-sei=Nakagoshi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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= en-keyword=Drosophila kn-keyword=Drosophila en-keyword=ecdysone kn-keyword=ecdysone en-keyword=fecundity kn-keyword=fecundity en-keyword=fertility kn-keyword=fertility en-keyword=nutrition kn-keyword=nutrition en-keyword=steroid kn-keyword=steroid 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=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=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=247 end-page=252 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=Post-Tracheostomy Fistula Formation Between the Trachea and Left Common Carotid Artery in a Pediatric Patient with Trisomy 18 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The long-term survival of individuals with trisomy 18 has improved, and the need for tracheostomy in this population has thus increased. We describe the case of a 3-year-old Japanese boy with trisomy 18 who developed a tracheoarterial fistula involving the left common carotid artery (LCCA). He underwent an emergency tracheostomy for respiratory failure secondary to pneumonia. Massive hemorrhage from the tracheostoma occurred on postoperative day 31, leading to his death. The autopsy revealed that the LCCA originated from the brachiocephalic trunk and coursed medially, forming a fistulous connection with the trachea. This case highlights the clinical importance of preoperative vascular mapping in patients with chromosomal abnormalities. en-copyright= kn-copyright= en-aut-name=ShiinaTsuyoshi en-aut-sei=Shiina en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeHirokazu en-aut-sei=Watanabe en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshimotoJunko en-aut-sei=Yoshimoto en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoTakeshi en-aut-sei=Sato en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MorimotoDaisaku en-aut-sei=Morimoto en-aut-mei=Daisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkamuraTomoka en-aut-sei=Okamura en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanimotoTerutaka en-aut-sei=Tanimoto en-aut-mei=Terutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=OyamaTakanori en-aut-sei=Oyama en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=NodaTakuo en-aut-sei=Noda en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pediatrics, Fukuyama City Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pediatric Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pediatric Surgery, Fukuyama City Hospital kn-affil= affil-num=10 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Pediatric Surgery, Japanese Red Cross Society Himeji Hospital kn-affil= en-keyword=tracheoarterial fistula kn-keyword=tracheoarterial fistula en-keyword=tracheocarotid fistula kn-keyword=tracheocarotid fistula en-keyword=trisomy 18 kn-keyword=trisomy 18 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=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=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=2 article-no= start-page=e79001 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250214 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Durable Response to Nivolumab Combined With Metformin in Advanced Pancreatic Cancer: A Case Report With Seven Years of Follow-Up en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a case of poorly differentiated pancreatic cancer that showed an exceptional response to combination therapy with nivolumab and metformin. A 58-year-old man presented with epigastric pain and was diagnosed with locally advanced pancreatic cancer with para-aortic lymph node metastasis. After disease progression following modified FOLFIRINOX therapy (a combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin), the patient was enrolled in a phase Ib clinical trial of nivolumab (3 mg/kg biweekly) combined with metformin (750 mg/day). Post-treatment imaging showed marked tumor shrinkage with normalization of the tumor markers. During treatment, the patient was diagnosed with early-stage lung cancer and underwent successful left S1+S2 segmentectomy with temporary suspension of immunotherapy. The therapeutic response of pancreatic cancer has been sustained for seven years, with minimal residual disease. This unprecedented response duration is particularly noteworthy considering his microsatellite stability, which typically predicts a limited response to immune checkpoint inhibition.
This case demonstrates an exceptional response to nivolumab and metformin combination therapy in poorly differentiated pancreatic cancer. The remarkable durability of the response suggests the need for further investigation to identify patients most likely to benefit from this therapeutic approach. 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=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 ORCID= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University kn-affil= affil-num=8 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=immune checkpoint inhibitors kn-keyword=immune checkpoint inhibitors en-keyword=immunotherapy kn-keyword=immunotherapy en-keyword=metformin kn-keyword=metformin en-keyword=nivolumab kn-keyword=nivolumab en-keyword=pancreatic cancer kn-keyword=pancreatic cancer 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=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= 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=229 cd-vols= no-issue= article-no= start-page=105080 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=Enhanced calcium activity and transcriptomic alterations in iPSC-derived neurons from BAFME patients with repeat expansions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Benign adult familial myoclonus epilepsy (BAFME) is caused by intronic TTTCA and TTTTA repeat expansions in SAMD12 and other genes; the neuronal basis of cortical hyperexcitability, however, remains unclear. We generated induced pluripotent stem cell (iPSC)-derived glutamatergic and GABAergic neurons from three BAFME1 patients and examined functional and transcriptomic phenotypes. Patient-derived neurons retained the pathogenic repeat expansions and showed a tendency toward upstream intronic RNA accumulation. Calcium imaging revealed increased spontaneous Ca2 + transient frequency in both neuronal subtypes, indicating heightened activity. Pharmacological profiling demonstrated attenuated responses to calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor (CP-AMPAR) blockade and GABAA receptor antagonism in GABAergic neurons, suggesting altered inhibitory signaling. RNA sequencing revealed transcriptomic alterations without differential expression of ion channels and neurotransmitter receptors. In glutamatergic neurons, ATF4-regulated genes, including SLC7A5 encoding LAT1, a Kv1.2 channel modulator, were downregulated. Reduced SLC7A5 expression was validated at both mRNA and protein levels. In GABAergic neurons, synapse-associated genes PTPRD and GPC6 were upregulated. TCERG1L and NLRP2 were suppressed across both neuronal subtypes. These findings suggest subtype-specific alterations may contribute to neuronal hyperexcitability in BAFME and provide a platform for mechanistic studies of repeat expansion-associated epilepsies. en-copyright= kn-copyright= en-aut-name=NagasakoYuki en-aut-sei=Nagasako en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshikawaMitsuru en-aut-sei=Ishikawa en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=SupakulSopak en-aut-sei=Supakul en-aut-mei=Sopak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaedaSumihiro en-aut-sei=Maeda en-aut-mei=Sumihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkanoHideyuki en-aut-sei=Okano en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Physiology, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Physiology, Keio University School of Medicine kn-affil= affil-num=5 en-affil=Department of Physiology, Keio University School of Medicine kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Physiology, Keio University School of Medicine kn-affil= en-keyword=Induced pluripotent stem cells kn-keyword=Induced pluripotent stem cells en-keyword=Glutamatergic neurons kn-keyword=Glutamatergic neurons en-keyword=GABAergic neurons kn-keyword=GABAergic neurons en-keyword=Calcium imaging kn-keyword=Calcium imaging en-keyword=BAFME kn-keyword=BAFME en-keyword=Repeat expansion kn-keyword=Repeat expansion en-keyword=Epilepsy kn-keyword=Epilepsy END start-ver=1.4 cd-journal=joma no-vol=83 cd-vols= no-issue=10 article-no= start-page=565 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260730 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Osmotic pressure, correlation lengths and viscosity of aqueous pullulan solutions beyond the overlap concentration en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigate the thermodynamic, scattering, and flow properties of pullulan, a flexible non-ionic polysaccharide in aqueous solution, focusing on semidilute and concentrated solutions. We review dilute solution data for the intrinsic viscosity and radius of gyration and hydrodynamic radius of aqueous pullulan and find the Kuhn length and thermal blob size, below which the polymer chain is nearly ideal, to be 3 nm and 20 nm, respectively. We establish the scaling laws for static correlation length, specific viscosity, osmotic pressure, and osmotic compressibility across dilute, semidilute, and concentrated regions, finding that the scaling exponents align well with theoretical predictions but the crossover concentrations obtained from different methods are not consistent. The ratio between the osmotic and Ornstein–Zernike correlation lengths ξΠ/ξOZ is approximately 2.5 for aqueous solutions, similar to that observed in polystyrene in a theta solvent. This similarity may arise because the crossover concentration between the semidilute and concentrated regions c∗∗ is close to the overlap concentration c∗. en-copyright= kn-copyright= en-aut-name=MengLingzi en-aut-sei=Meng en-aut-mei=Lingzi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwatoRene en-aut-sei=Iwato en-aut-mei=Rene kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeTakaichi en-aut-sei=Watanabe en-aut-mei=Takaichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LopezCarlos G. en-aut-sei=Lopez en-aut-mei=Carlos G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Materials Science and Engineering, The Pennsylvania State 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 Materials Science and Engineering, The Pennsylvania State University kn-affil= en-keyword=Pullulan kn-keyword=Pullulan en-keyword=Osmotic pressure kn-keyword=Osmotic pressure en-keyword=Correlation length kn-keyword=Correlation length en-keyword=Semidilute solutions kn-keyword=Semidilute solutions en-keyword=Concentrated solutions kn-keyword=Concentrated solutions en-keyword=Viscosity kn-keyword=Viscosity en-keyword=SAXS kn-keyword=SAXS en-keyword=SANS kn-keyword=SANS en-keyword=DLS kn-keyword=DLS END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e02824-25 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260724 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Escalation of CTX-M-producing extensively drug-resistant Shigella spp. in Kolkata, India, following the COVID-19 pandemic en-subtitle= kn-subtitle= en-abstract= kn-abstract=Shigella spp. is recognized by the World Health Organization as a high-priority pathogen due to its global prevalence, unique pathogenic mechanisms, and growing antimicrobial resistance (AMR). Nearly half of all Shigella strains worldwide are now multidrug-resistant (MDR), and the emergence of extensively drug-resistant (XDR) variants—resistant to ciprofloxacin, ceftriaxone, and azithromycin—has severely limited effective treatment options. The present study is based on prospective laboratory surveillance involving 323 Shigella isolates collected during 2021–2023, with pre-COVID-19 pandemic data included from a previously published study solely for historical comparison. The presence of antibiotic resistance genes (ARGs) was investigated, and whole-genome sequencing (WGS) was performed on representative isolates to assess phylogenetic relatedness with global isolates. Approximately 10% of isolates exhibited resistance to third-generation cephalosporins. While only 3% of Shigella isolates carried the blaCTX-M-15 gene from 2013 to 2019, its prevalence increased to 26% by 2022–2023. Among 38 ceftriaxone-resistant S. sonnei isolates, 33 were also resistant to azithromycin, categorizing them as XDR. These isolates showed 48% clonal similarity and high phylogenetic resemblance to the isolates reported from England. Hybrid genome assembly revealed a plasmid harboring both the blaCTX-M-15 and mphA ARGs. Conjugation experiments and plasmid profiling confirmed the plasmid’s transferability. We report a rising trend in third-generation cephalosporin resistance among Shigella spp., primarily driven by the spread of extended-spectrum β-lactamase-producing S. flexneri and the emergence of XDR S. sonnei. These findings underscore the urgent need for strengthened national AMR containment strategies and enhanced international surveillance of cephalosporin-resistant Shigella to mitigate this growing public health threat. en-copyright= kn-copyright= en-aut-name=BosePuja en-aut-sei=Bose en-aut-mei=Puja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HalderGourab en-aut-sei=Halder en-aut-mei=Gourab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KayetPratanu en-aut-sei=Kayet en-aut-mei=Pratanu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChowdhuryGoutam en-aut-sei=Chowdhury en-aut-mei=Goutam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BasakSurajit en-aut-sei=Basak en-aut-mei=Surajit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=RoyDeboleena en-aut-sei=Roy en-aut-mei=Deboleena 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=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoritaMasatomo en-aut-sei=Morita en-aut-mei=Masatomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=RamamurthyThandavarayan en-aut-sei=Ramamurthy en-aut-mei=Thandavarayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KoleyHemanta en-aut-sei=Koley en-aut-mei=Hemanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DasSantasabuj en-aut-sei=Das en-aut-mei=Santasabuj kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MukhopadhyayAsish Kumar en-aut-sei=Mukhopadhyay en-aut-mei=Asish Kumar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=2 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=3 en-affil=Division of Bioinformatics, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=4 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=5 en-affil=Division of Bioinformatics, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=6 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=7 en-affil=Research Center for Intestinal Health Science, Okayama University kn-affil= affil-num=8 en-affil=Research Center for Intestinal Health Science, Okayama University kn-affil= affil-num=9 en-affil=Department of Bacteriology I, National Institute of Infectious Diseases kn-affil= affil-num=10 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=11 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=12 en-affil=Division of Clinical Medicine, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=13 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections kn-affil= en-keyword=dysentery kn-keyword=dysentery en-keyword=AMR kn-keyword=AMR en-keyword=XDR kn-keyword=XDR en-keyword=Shigella spp. kn-keyword=Shigella spp. en-keyword=CTX-M kn-keyword=CTX-M en-keyword=plasmid kn-keyword=plasmid en-keyword=transconjugants kn-keyword=transconjugants en-keyword=PFGE kn-keyword=PFGE en-keyword=WGS kn-keyword=WGS END start-ver=1.4 cd-journal=joma no-vol=84 cd-vols= no-issue= article-no= start-page=102895 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=Factors that delay discovery in cases of death at home in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=In Japan, solitary deaths have become a social issue, with an increasing number of cases in which the body is discovered long after death. This study aimed to clarify the factors underlying such delays. Cases of death at home were extracted from forensic autopsies. In each case, we collected information about the deceased and their living conditions. The postmortem interval until finding (PMI-f) was calculated by measuring the time between death and discovery. We classified the cases into long PMI-f (LPMI-f; having PMI-f of ≥3 days) and short PMI-f (SPMI-f; having PMI-f of <3 days), and examined the factors that lead to LPMI-f. The characteristics of the group living alone with a PMI-f of <24 h and living with family or acquaintances with an LPMI-f were also analyzed. Among the 420 cases included, 244 (58.1%) were in the LPMI-f group. The LPMI-f group had higher number of males; older individuals; those living alone; those found inside their homes; single, retired, or non-employed individuals; those without long-term care certification; and those with drinking habits. Forty-seven individuals lived alone and had PMI-f of <24 h. Regular visits from relatives living separately led to early detection after death. In the LPMI-f group, 56 individuals lived with family or acquaintances. The absence of regular visits can result in delayed discovery after death; however, the time between death and discovery could be shortened by implementing systems such as allowing neighbors to check the person's safety by noticing uncollected mail. en-copyright= kn-copyright= en-aut-name=YamasakiYukie en-aut-sei=Yamasaki en-aut-mei=Yukie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TamiyaNanako en-aut-sei=Tamiya en-aut-mei=Nanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiuraMasanobu en-aut-sei=Miura en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaniguchiKaori en-aut-sei=Taniguchi en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiChie en-aut-sei=Kobayashi en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MotomuraMasafumi en-aut-sei=Motomura en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Himemiya-HakuchoAyako en-aut-sei=Himemiya-Hakucho en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyaishiSatoru en-aut-sei=Miyaishi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Health Services Research, Faculty of Medicine, University of Tsukuba kn-affil= affil-num=3 en-affil=Department of Environmental Health, Faculty of Pharma-Science, Teikyo University kn-affil= affil-num=4 en-affil=Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Solitary deaths kn-keyword=Solitary deaths en-keyword=Social isolation kn-keyword=Social isolation en-keyword=Postmortem interval kn-keyword=Postmortem interval en-keyword=Decomposition kn-keyword=Decomposition END start-ver=1.4 cd-journal=joma no-vol=134 cd-vols= no-issue=7 article-no= start-page=455 end-page=460 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dielectric response modulation in relaxor (Sr,Ba)Nb2O6 via engineered defect en-subtitle= kn-subtitle= en-abstract= kn-abstract=Defect engineering provides an effective pathway to tune the dielectric response of relaxor ferroelectrics, yet the roles of individual defect species in tungsten bronze (TTB) systems remain unclear. Here, we investigated how engineered Ti–VO•• defect dipoles and native oxygen vacancies introduced through reduction annealing modify the dielectric properties of relaxor (Sr0.5,Ba0.5)Nb2O6 (0.5-SBN). Ti loading forms stable defect dipoles that generate smaller polar nanoregions (PNRs), suppress their overgrowth, and increase the number of dynamically active PNRs at room temperature, leading to enhanced permittivity ε′ while preserving DC-bias stability and breakdown strength (EB). Reduction annealing generates Nb4+-related local polarizations aligned with the external electric field, which strengthen dipole fluctuations and slightly increase ε′. Electron localization further relaxes the TTB-A2 site disorder–induced random fields, yielding a sharper dielectric peak and promoting more uniform PNR growth. Microwave dielectric spectroscopy combined with electromagnetic simulations revealed that the increases in ε′ for both Ti-loaded and reduced samples (0.5-SBNT and Reduced 0.5-SBN, respectively) originate predominantly from enhanced dipole polarization. Despite grain coarsening in 0.5-SBNT, the EB remained unchanged, indicating that defect dipoles act as pinning centers that inhibit field-induced PNR aggregation. In reduced 0.5-SBN, EB increased up to pO0 = 4.3 × 10−3 atm owing to relaxed random fields, whereas excessive reduction reduced EB through carrier-driven space-charge effects. These results demonstrate that precise control of defect species enables simultaneous optimization of ε′, DC-bias stability, and EB in TTB-type relaxor ferroelectrics. en-copyright= kn-copyright= en-aut-name=ShiotaRyusei en-aut-sei=Shiota en-aut-mei=Ryusei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeranishiTakashi en-aut-sei=Teranishi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoShinya en-aut-sei=Kondo en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KishimotoAkira en-aut-sei=Kishimoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Energy Engineering, Nagoya University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Relaxor ferroelectrics kn-keyword=Relaxor ferroelectrics en-keyword=(Sr,Ba)Nb2O6 kn-keyword=(Sr,Ba)Nb2O6 en-keyword=Polar nanoregions kn-keyword=Polar nanoregions en-keyword=Dipole polarization kn-keyword=Dipole polarization en-keyword=DC bias response kn-keyword=DC bias response END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=2 article-no= start-page=228 end-page=236 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Acquired LCAT Deficiency with the Discrepancy between Spontaneous Resolution of Proteinuria and Continually Low HDL Cholesterol Levels en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 79-year-old Chinese man was referred for nephrotic syndrome (proteinuria 4.4 g/day). In blood tests, serum high-density lipoprotein (HDL) cholesterol was undetectable, and the esterified cholesterol to total cholesterol ratio was very low. Lecithin: cholesterol acyltransferase (LCAT) activity was also undetectable. Since he had neither corneal opacity nor pathological mutations in the LCAT gene and anti-LCAT antibodies were detected in serum, a diagnosis of acquired LCAT deficiency was made. Renal biopsy revealed glomerulopathy associated with LCAT deficiency and membranous nephropathy (MN). Since the patient’s proteinuria did not improve despite prescribing an angiotensin II receptor blocker (ARB), we suggested the prescription of prednisolone, but he returned to China due to the expiration of his residence visa for Japan. One year after the initial visit, his proteinuria had improved to 0.9 g/day without immunosuppressive therapy. However, his HDL cholesterol level was still low at around 3 mg/dL, indicating a discrepancy between remission of nephrotic syndrome and lack of improvement in lipid levels.
Of the 11 patients with acquired LCAT deficiency reported to date, 4 with undetectable LCAT activity and MN on renal biopsy required immunosuppressive therapy to alleviate proteinuria. The present patient was prescribed only an ARB according to his preference, which happened to be consistent with the MN treatment guideline that states, “Wait 6 months for spontaneous remission while using maximal antiproteinuric therapy.” The clinical course of acquired LCAT deficiency varies, and further case reports are needed to determine the necessity of immunosuppressive therapy. en-copyright= kn-copyright= en-aut-name=MatsuoMiki en-aut-sei=Matsuo en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OguraMasatsune en-aut-sei=Ogura en-aut-mei=Masatsune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurodaMasayuki en-aut-sei=Kuroda en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArisatoTetsuya en-aut-sei=Arisato en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KishidaMasatsugu en-aut-sei=Kishida en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Harada-ShibaMariko en-aut-sei=Harada-Shiba en-aut-mei=Mariko 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= en-aut-name=YokoteKoutaro en-aut-sei=Yokote en-aut-mei=Koutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshiharaFumiki en-aut-sei=Yoshihara en-aut-mei=Fumiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Nephrology and Hypertension, National Cerebral and Cardiovascular Center kn-affil= affil-num=2 en-affil=Department of Clinical Laboratory Technology, Faculty of Medical Science, Juntendo University kn-affil= affil-num=3 en-affil=Center for Advanced Medicine, Chiba University Hospital, Chiba University kn-affil= affil-num=4 en-affil=Department of Nephrology and Hypertension, National Cerebral and Cardiovascular Center kn-affil= affil-num=5 en-affil=Department of Nephrology and Hypertension, National Cerebral and Cardiovascular Center kn-affil= affil-num=6 en-affil=Cardiovascular Center, Osaka Medical and Pharmaceutical University kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Nephrology and Hypertension, National Cerebral and Cardiovascular Center kn-affil= en-keyword=Acquired LCAT deficiency kn-keyword=Acquired LCAT deficiency en-keyword=HDL deficiency kn-keyword=HDL deficiency en-keyword=Nephrotic syndrome kn-keyword=Nephrotic syndrome en-keyword=Membranous glomerulonephritis kn-keyword=Membranous glomerulonephritis 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=87 cd-vols= no-issue=5 article-no= start-page=429 end-page=433 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=Cardio-ankle vascular index as a screening tool for coronary artery disease in patients with metabolic dysfunction-associated steatotic liver disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common hepatic disorder that significantly increases cardiovascular risk. However, no established screening method exists for detecting subclinical coronary artery disease (CAD) in this high-risk population. The cardio-ankle vascular index (CAVI), a blood pressure–independent measure of arterial stiffness, may offer a non-invasive tool for early detection of coronary atherosclerosis.
Methods: We retrospectively analyzed 295 patients with MASLD who underwent both CAVI measurement and coronary computed tomography angiography at a single center. Significant CAD was defined as ≥50 % luminal stenosis. Receiver operating characteristic (ROC) analysis was used to evaluate diagnostic performance. Multivariable logistic regression was performed to identify independent associations between elevated CAVI and CAD. The incremental predictive value of CAVI was assessed using net reclassification improvement (NRI).
Results: Of the 295 patients, 110 (37.3 %) had significant CAD. Patients with CAD had significantly higher CAVI values (9.0 vs. 8.7, p = 0.007). The area under the ROC curve for CAVI predicting CAD was 0.614. A CAVI cut-off of 8.6 provided a sensitivity of 66.4 % and a specificity of 56.8 %. CAVI ≥8.0 was independently associated with CAD (OR 3.44, 95 % CI: 1.06–11.2, p = 0.040). Adding CAVI to a conventional risk model improved risk reclassification (NRI 0.4236, p < 0.001), although the C-statistic change was not significant (from 0.724 to 0.725, p = 0.835).
Conclusions: CAVI is independently associated with significant coronary stenosis in MASLD patients and may serve as a non-invasive screening tool to enhance cardiovascular risk stratification. Its moderate diagnostic accuracy suggests utility as a component of a multifactorial risk assessment strategy. en-copyright= kn-copyright= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UekiYuta en-aut-sei=Ueki en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishiharaTakahiro en-aut-sei=Nishihara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MikiTakashi en-aut-sei=Miki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaraShohei en-aut-sei=Hara en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IchikawaKeishi en-aut-sei=Ichikawa en-aut-mei=Keishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OsawaKazuhiro en-aut-sei=Osawa en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School General Medicine Centre kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Cardio-ankle vascular index kn-keyword=Cardio-ankle vascular index en-keyword=Steatotic liver kn-keyword=Steatotic liver en-keyword=Coronary artery disease kn-keyword=Coronary artery disease en-keyword=Arterial stiffness kn-keyword=Arterial stiffness en-keyword=Screening kn-keyword=Screening 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=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=32 cd-vols= no-issue=4 article-no= start-page=454 end-page=465 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=Spatial Transcriptomics Analysis of Macrophage-to-Myofibroblast Transition in Bronchiolitis Obliterans Following Hematopoietic Stem Cell Transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bronchiolitis obliterans (BO) is a severe, fibrotic manifestation of chronic graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Macrophage-derived TGF-β is linked to GVHD-related fibrosis; however, its role in BO remains unclear. Given emerging evidence of macrophage-to-myofibroblast transition (MMT) in fibrosis, this study aimed to investigate whether MMT contributes to BO development. We analyzed lung samples from 3 HSCT recipients with BO who underwent lung transplantation, with tissues from 2 patients with lung cancer as controls. Immunofluorescent staining for CD68, CD206, and α-SMA was used to identify cells undergoing MMT. Spatial transcriptomics was performed to profile gene expression in foamy macrophages across anatomical regions and histological stages, compared to control peribronchiolar regions. Immunostaining showed strong co-expression of CD68, CD206, and α-SMA in foamy macrophages within and surrounding bronchioles in BO samples, with minimal expression in controls, suggesting MMT involvement. In BO, spatial transcriptomics revealed upregulation of macrophage- and TGF-β signaling genes, with distinct stage- and region-specific gene expression patterns. Unsupervised clustering revealed a shift from inflammation to fibrosis. These findings indicate that MMT contributes to fibrosis in BO. Gene expression shifts from inflammation to fibrosis as the disease advances, underscoring the importance of early intervention. en-copyright= kn-copyright= en-aut-name=YamamotoAkira en-aut-sei=Yamamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=NaoiYusuke en-aut-sei=Naoi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NaganoTomohiro en-aut-sei=Nagano en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KubotaSaya en-aut-sei=Kubota en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KambaraYui en-aut-sei=Kambara en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraKanako en-aut-sei=Fujiwara en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TeraoToshiki en-aut-sei=Terao en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OyamaTadashi en-aut-sei=Oyama en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KunihiroMari en-aut-sei=Kunihiro en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 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=20 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama 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 Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=19 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=Bronchiolitis obliterans kn-keyword=Bronchiolitis obliterans en-keyword=GeoMx kn-keyword=GeoMx en-keyword=Graft versus host disease kn-keyword=Graft versus host disease en-keyword=Hematopoietic stem cell transplantation kn-keyword=Hematopoietic stem cell transplantation en-keyword=Macrophage kn-keyword=Macrophage en-keyword=Macrophage to myofibroblast transition kn-keyword=Macrophage to myofibroblast transition en-keyword=Myofibroblast kn-keyword=Myofibroblast en-keyword=Spatial transcriptomics kn-keyword=Spatial transcriptomics END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=3 article-no= start-page=107 end-page=115 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260315 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Full-endoscopic Laminotomy Is Effective for Lumbar Spinal Stenosis with Low-grade Spondylolisthesis: A Comparative Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The optimal management of lumbar spinal canal stenosis with spondylolisthesremains controversial, particularly when choosing between decompression alone or decompression with fusion. Current evidence is based on conventional open or endoscopy-assisted surgeries, with limited data on full-endoscopic decompression. This study aimed to assess the impact of spondylolisthesis on outcomes after full-endoscopic laminotomy by evaluating back pain-related disability scores in patients with lumbar spinal canal stenosis, with and without spondylolisthesis. A retrospective analysis was conducted at Iwai Orthopaedic Hospital, Japan. Patients with lumbar spinal canal stenosis who underwent full-endoscopic laminotomy between January 2021 and December 2022 were included and categorized into those without spondylolisthesis and those with spondylolisthesis. Postoperative Oswestry Disability Index scores at 2 years were compared in the groups using multivariable linear regression, adjusting for confounding factors. Exploratory analyses were also conducted to identify factors affecting the Oswestry Disability Index in the patients with lumbar spinal canal stenosis with spondylolisthesis group. Statistical significance was set at p < 0.05. The study included 80 patients, with 40 in each group. Both groups showed improved postoperative Oswestry Disability Index. There was no significant association between spondylolisthesis and postoperative Oswestry Disability Index. However, cauda equina redundancy negatively affected postoperative Oswestry Disability Index improvement in the patients with lumbar spinal canal stenosis with spondylolisthesis group. Full-endoscopic laminotomy is an effective surgical option for lumbar spinal canal stenosis, leading to significant alleviation of disability and improvements in quality of life, regardless of spondylolisthesis. Full-endoscopic laminotomy may offer similar functional improvements regardless of the presence of low-grade spondylolisthesis, supporting its role as a less invasive alternative to fusion. en-copyright= kn-copyright= en-aut-name=KINKyohei en-aut-sei=KIN en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TOMINAGARyoji en-aut-sei=TOMINAGA en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TAKEBAYASHIKento en-aut-sei=TAKEBAYASHI en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IWAIHiroki en-aut-sei=IWAI en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=INANAMIHirohiko en-aut-sei=INANAMI en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KOGAHisashi en-aut-sei=KOGA en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopaedics, Iwai Orthopaedic Medical Hospital kn-affil= affil-num=3 en-affil=Department of Orthopaedics, Iwai Orthopaedic Medical Hospital kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedics, Iwai Orthopaedic Medical Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedics, Iwai Orthopaedic Medical Hospital kn-affil= en-keyword=full-endoscopic spine surgery kn-keyword=full-endoscopic spine surgery en-keyword=spondylolisthesis kn-keyword=spondylolisthesis en-keyword=full-endoscopic laminotomy kn-keyword=full-endoscopic laminotomy en-keyword=minimally invasive kn-keyword=minimally invasive en-keyword=lumbar spinal canal stenosis kn-keyword=lumbar spinal canal stenosis END start-ver=1.4 cd-journal=joma no-vol=114 cd-vols= no-issue=3 article-no= start-page=486 end-page=489 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Heavy Paragonimiasis Involving a Multi-Organ Presentation with Hypereosinophilia and Hepatic Migration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Paragonimiasis is a parasitic disease caused by the genus Paragonimus, typically transmitted through the ingestion of raw or undercooked freshwater crabs. Although pulmonary involvement is typical, ectopic migration to subcutaneous or hepatic sites is rare and poses diagnostic challenges. A case of paragonimiasis in a 29-year-old Cambodian woman residing in Japan who presented with painless subcutaneous nodules on the chest and abdomen is reported in the current study. She had consumed raw crab 4 months before presentation. Laboratory findings revealed marked eosinophilia (21,000/µL) and elevated immunoglobulin E (5,049 IU/mL). Computed tomography scans revealed pleural effusion, club-shaped pulmonary consolidation, funicular hypodense lesions in the liver, and subcutaneous lesions. Stool and sputum test results were negative for parasite eggs; however, a microplate ELISA indicated a Paragonimus westermani infection. The patient responded well to 3 consecutive days of praziquantel (75 mg/kg/day) and was discharged a week later. This case highlights the importance of considering paragonimiasis in patients with unexplained subcutaneous nodules and eosinophilia, especially when supported by dietary risk factors. en-copyright= kn-copyright= en-aut-name=AkazawaHidemasa en-aut-sei=Akazawa en-aut-mei=Hidemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamotoKenta en-aut-sei=Nakamoto en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ManabeYohei en-aut-sei=Manabe en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Kokubo-TanakaMio en-aut-sei=Kokubo-Tanaka en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaruyamaHaruhiko en-aut-sei=Maruyama en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Parasitology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki kn-affil= affil-num=8 en-affil=Division of Parasitology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki kn-affil= affil-num=9 en-affil=Department of General Medicine, Okayama University Hospital kn-affil= 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=2026 cd-vols= no-issue=1 article-no= start-page=2879891 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=A Rare Case of Hyperplastic Dental Follicle Presenting With an Unusually Large Radiolucent Area en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hyperplastic dental follicle (HDF) is a rare odontogenic hamartomatous lesion typically associated with unerupted teeth in children and adolescents and is often found incidentally on radiographic imaging. HDF usually presents as a pericoronal radiolucency of 2–3 mm in diameter and is commonly difficult to distinguish from dentigerous cysts on radiographs. We report an unusual case of HDF in an 11-year-old male who was referred for evaluation of delayed eruption of the left maxillary canine. Panoramic radiography and cone-beam computed tomography (CBCT) revealed a remarkably large radiolucent area, with a maximum dimension of 25.3 mm. The initial clinical diagnosis was a dentigerous cyst; however, incisional biopsy revealed solid tissue characteristics, and histopathological examination confirmed HDF, with no evidence of cystic lining, neoplastic transformation, or inflammation. Following the patient′s and parents′ preference for complete removal, resection of the lesion together with extraction of the impacted canine was performed under general anesthesia. At the 6-month follow-up, no recurrence was observed and bone regeneration was confirmed on radiographic examination. This case underscores the diagnostic challenge posed by atypical radiographic findings and highlights the necessity of histopathological confirmation. Given the exceptional size and potential for recurrence, long-term follow-up is warranted. en-copyright= kn-copyright= en-aut-name=OtsukiSatoshi en-aut-sei=Otsuki en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=KobayashiChizuru en-aut-sei=Kobayashi en-aut-mei=Chizuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=KawazuToshiyuki en-aut-sei=Kawazu en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=case report kn-keyword=case report en-keyword=hyperplastic dental follicle kn-keyword=hyperplastic dental follicle en-keyword=large radiolucent lesion kn-keyword=large radiolucent lesion en-keyword=odontogenic hamartoma kn-keyword=odontogenic hamartoma en-keyword=unerupted tooth kn-keyword=unerupted tooth END start-ver=1.4 cd-journal=joma no-vol=225 cd-vols= no-issue= article-no= start-page=111049 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=Decline in rescue breathing and its impact on outcomes in pediatric out-of-hospital cardiac arrest due to drowning: a nationwide study, 2012–2023 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Rescue breathing is considered essential in pediatric out-of-hospital cardiac arrest (OHCA) due to drowning, a type of asphyxial arrest where hypoxia precedes circulatory collapse. However, the increasing promotion of compression-only CPR (CO-CPR) may have contributed to changes in bystander CPR practices, including a decline in rescue-breathing CPR (RB-CPR). Whether such temporal changes have influenced outcomes in pediatric drowning OHCA remains unclear.
Methods: We analyzed nationwide data from the All-Japan Utstein Registry (2012–2023), including pediatric OHCA patients (≤17 years old) whose arrests were caused by drowning and received bystander CPR from laypersons. Patients were categorized into RB-CPR and CO-CPR groups. The primary outcome was 30-day mortality; secondary outcomes included prehospital absence of return of spontaneous circulation (ROSC) and 30-day unfavorable neurological survival, defined as Cerebral Performance Category score 3–5. We used multivariable Poisson regression to estimate adjusted risk ratio (aRR) and conducted analyses by age and witnessed status.
Results: Among 740 eligible patients, 41.6% received RB-CPR and 58.4% received CO-CPR. The proportion of RB-CPR declined over the study period. CO-CPR was associated with higher 30-day mortality (aRR 1.38, 95% CI 1.14–1.67), higher prehospital absence of ROSC, and worse neurological outcomes compared with RB-CPR. The adverse association of CO-CPR was most pronounced in unwitnessed arrests, where ventilation may be particularly important.
Conclusions: In pediatric drowning OHCA, CO-CPR was associated with worse survival and neurological outcomes than RB-CPR. These findings underscore the necessity for rescue breathing and the importance of ventilation-focused bystander CPR training in pediatric and drowning-related scenarios. en-copyright= kn-copyright= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HongoTakashi en-aut-sei=Hongo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=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= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=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 Epidemiology, 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 Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, 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=Drowning kn-keyword=Drowning en-keyword=Out-of-hospital cardiac arrest kn-keyword=Out-of-hospital cardiac arrest en-keyword=Cardiopulmo naryresuscitation kn-keyword=Cardiopulmo naryresuscitation en-keyword=Child kn-keyword=Child en-keyword=Asphyxia kn-keyword=Asphyxia END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=3 article-no= start-page=ruag033 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=Estimating the distributional expansion of the invasive crayfish Procambarus clarkii (Girard, 1852) (Decapoda: Astacidea: Cambaridae) in South Korea using environmental DNA analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=The red swamp crayfish Procambarus clarkii (Girard, 1852) is a globally invasive species that poses serious threats to native biodiversity and ecosystem functioning. In South Korea, established populations of P. clarkii have been documented from the Jiseokcheon River in the Yeongsangang River basin since 2018; however, information on its current nationwide distribution remains limited. We conducted environmental DNA (eDNA) surveys at 19 sites across 11 river systems in South Korea, including sites with no prior distributional records, to evaluate the current distribution and potential range expansion of P. clarkii. Water samples collected during July-August 2024 were analyzed using quantitative real-time PCR (qPCR) with two species-specific primer-probe sets targeting the mitochondrial COI gene. Procambarus clarkii eDNA was detected at three sites in the Yeongsangang River basin, whereas no eDNA was detected in the other surveyed river systems. Notably, P. clarkii eDNA was not detected at a site in the Mangyeonggang River system despite previous reports of individuals and eDNA data sampled there, indicating a possible local population decline or very low abundance. By contrast, detections within the Yeongsangang River basin, together with elevated eDNA concentrations at some sites, are consistent with localized upstream expansion and increased local abundance. The concordant results from the two primer-probe sets, together with Sterivex-based on-site filtration, support the reliability of the applied eDNA framework. These findings identify the Yeongsangang River basin as the current primary focus of the P. clarkii invasion in South Korea, with evidence consistent with localized upstream expansion and increasing abundance, and provide baseline data for early detection and long-term monitoring, as well as for developing management strategies. en-copyright= kn-copyright= en-aut-name=HamSeong-Nam en-aut-sei=Ham en-aut-mei=Seong-Nam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriuchiKaito en-aut-sei=Moriuchi en-aut-mei=Kaito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=NakataKazuyoshi en-aut-sei=Nakata en-aut-mei=Kazuyoshi 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=Crustacea kn-keyword=Crustacea en-keyword=early detection kn-keyword=early detection en-keyword=eDNA kn-keyword=eDNA en-keyword=freshwater ecosystems kn-keyword=freshwater ecosystems en-keyword=red swamp crayfish kn-keyword=red swamp crayfish END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=22 article-no= start-page=e202504108 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficient Nickel Precatalysts for Suzuki-Miyaura Cross-Coupling of Aryl Chlorides and Arylboronic Acids Under Mild Conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=The synthesis and catalytic properties of Ni(II) complexes with the general formula Ni(NHC)[P(OR)3](Ar)Cl are described. These complexes are air-stable and extremely effective precatalysts in the Suzuki-Miyaura cross-coupling reaction. The reaction protocols described allow for the cross-coupling of aryl chlorides and arylboronic acids, employing low catalytic loading, to deliver a large variety of functionalized biaryl compounds. For the coupling of aryl chlorides with N-heterocyclic boronic acids, TBAF was used as an additive to afford nitrogen-containing biaryl products. Overall, these reaction protocols operate at room or mild temperatures and can be applied to a variety of electronically and sterically differentiated coupling partners. Fundamental insights into the mechanism of this reaction, including the proposed formation of the catalytically active Ni(NHC)[P(Oi-Pr)3] and resting state species, are also reported. en-copyright= kn-copyright= en-aut-name=JohnMorgan E. en-aut-sei=John en-aut-mei=Morgan E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NuttMichael J. en-aut-sei=Nutt en-aut-mei=Michael J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OfferJosephine E. en-aut-sei=Offer en-aut-mei=Josephine E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DuczynskiJeremy A. en-aut-sei=Duczynski en-aut-mei=Jeremy A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamazakiKen en-aut-sei=Yamazaki en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiuraTomoya en-aut-sei=Miura en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MoggachStephen A. en-aut-sei=Moggach en-aut-mei=Stephen A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoutsantonisGeorge A. en-aut-sei=Koutsantonis en-aut-mei=George A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DortaReto en-aut-sei=Dorta en-aut-mei=Reto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=StewartScott G. en-aut-sei=Stewart en-aut-mei=Scott G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=School of Molecular Sciences, The University of Western Australia (M310) kn-affil= affil-num=2 en-affil=School of Molecular Sciences, The University of Western Australia (M310) kn-affil= affil-num=3 en-affil=School of Molecular Sciences, The University of Western Australia (M310) kn-affil= affil-num=4 en-affil=School of Molecular Sciences, The University of Western Australia (M310) kn-affil= affil-num=5 en-affil=Division of Applied Chemistry, Okayama University kn-affil= affil-num=6 en-affil=Division of Applied Chemistry, Okayama University kn-affil= affil-num=7 en-affil=School of Molecular Sciences, The University of Western Australia (M310) kn-affil= affil-num=8 en-affil=School of Molecular Sciences, The University of Western Australia (M310) kn-affil= affil-num=9 en-affil=School of Molecular Sciences, The University of Western Australia (M310) kn-affil= affil-num=10 en-affil=School of Molecular Sciences, The University of Western Australia (M310) kn-affil= en-keyword=Air Stable kn-keyword=Air Stable en-keyword=Aryl Chlorides kn-keyword=Aryl Chlorides en-keyword=Boronic Acids kn-keyword=Boronic Acids en-keyword=Nickel Catalysis kn-keyword=Nickel Catalysis en-keyword=Room Temperature kn-keyword=Room Temperature en-keyword=Suzuki-Miyaura Cross-Coupling kn-keyword=Suzuki-Miyaura Cross-Coupling END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=5485 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260402 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bacterial collagenase harnesses collagen geometry for processive cleavage en-subtitle= kn-subtitle= en-abstract= kn-abstract=Collagen, the major structural protein in the animal extracellular matrix, forms a triple helix that resists proteolysis and requires specialised enzymes for degradation. Flesh-eating bacteria secrete collagenases that unwind the collagen triple helix and processively trim Gly–X–Y triplet repeats, yet the molecular basis of this process has remained obscure. Here, cryo-electron microscopy reveals how Hathewaya histolytica collagenase ColH engages its substrate and exploits the helix’s architecture for catalysis. ColH encircles a single collagen triple helix in a closed-ring conformation and, through dynamic domain motions, dehydrates and destabilises it. The enzyme undergoes substrate-assisted twisting to adopt a rigid ratcheted conformation, in which one chain is bent into a tripeptide-long ‘bight’ and threaded into the active site for cleavage, while two uncut strands are partitioned to non-catalytic sites. Release of the bight appears to reset the enzyme, with the uncut strands serving as guiding tracks. Repeated cycling between dynamic and rigid states likely enables triplet-by-triplet translocation, allowing ColH to harness collagen’s geometry for processive degradation. These findings reveal a bacterial strategy for collagen unwinding and cleavage distinct from that of mammalian collagenases, highlighting divergent evolutionary solutions for degrading one of nature’s most intractable substrates. en-copyright= kn-copyright= en-aut-name=OkiHiroya en-aut-sei=Oki en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakebeKatsuki en-aut-sei=Takebe en-aut-mei=Katsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BonsuAdjoa en-aut-sei=Bonsu en-aut-mei=Adjoa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiKazunori en-aut-sei=Fujii en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasudaRyo en-aut-sei=Masuda en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HendersonNicholas en-aut-sei=Henderson en-aut-mei=Nicholas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MimaTakehiko en-aut-sei=Mima en-aut-mei=Takehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoideTakaki en-aut-sei=Koide en-aut-mei=Takaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoradiMahmoud en-aut-sei=Moradi en-aut-mei=Mahmoud kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsushitaOsamu en-aut-sei=Matsushita en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakonJoshua en-aut-sei=Sakon en-aut-mei=Joshua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawaharaKazuki en-aut-sei=Kawahara en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, The University of Osaka kn-affil= affil-num=2 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry and Biochemistry, University of Arkansas kn-affil= affil-num=4 en-affil=Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University kn-affil= affil-num=5 en-affil=Waseda Research Institute for Science and Engineering, Waseda University kn-affil= affil-num=6 en-affil=Department of Chemistry and Biochemistry, University of Arkansas kn-affil= affil-num=7 en-affil=Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences kn-affil= affil-num=8 en-affil=Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University kn-affil= affil-num=9 en-affil=Department of Chemistry and Biochemistry, University of Arkansas kn-affil= affil-num=10 en-affil=Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Chemistry and Biochemistry, University of Arkansas kn-affil= affil-num=12 en-affil=Graduate School of Pharmaceutical Sciences, The University of Osaka kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=19282 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260427 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dual-calibration RT-qPCR reveals distinct dnaK1/2/3 and groEL1/2 expression dynamics under heat and acid stress in the sinefungin producer Streptomyces incarnatus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Streptomyces incarnatus NRRL8089 produces sinefungin, a nucleoside antibiotic whose yield is enhanced under defined environmental stresses. Here, dual-calibration RT-qPCR was used to resolve paralogue-specific expression dynamics of the dnaK and groE chaperone systems under heat and acid stress conditions that increase sinefungin titres. The canonical dnaK1–dnaJ1 and groES–groEL1 operons exhibited moderate induction, whereas monocistronic paralogues (dnaK2, dnaK3 and groEL2) showed markedly higher inducibility, with up to ~ 125-fold increases relative to baseline expression. Promoter analyses revealed conserved inverted repeats and differences in predicted secondary-structure stability, suggesting that promoter architecture contributes to paralogue-specific responsiveness. Structural modelling indicated divergence among DnaK paralogues in regions associated with substrate interaction, whereas GroEL paralogues retained a conserved overall scaffold, consistent with kinetic rather than structural differentiation. Together, these findings indicate that duplicated paralogues are not functionally redundant but are differentially regulated to partition proteostasis capacity under stress. This paralogue-specific regulation may provide a framework linking environmental perturbation to secondary-metabolite production in actinomycetes. en-copyright= kn-copyright= en-aut-name=Xiao-HuiZhao en-aut-sei=Xiao-Hui en-aut-mei=Zhao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuboMao en-aut-sei=Kubo en-aut-mei=Mao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamagataHaruka en-aut-sei=Yamagata en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakashimaYuriko en-aut-sei=Nakashima en-aut-mei=Yuriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HasunumaTomohisa en-aut-sei=Hasunuma en-aut-mei=Tomohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KanaoTadayoshi en-aut-sei=Kanao en-aut-mei=Tadayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TamuraTakashi en-aut-sei=Tamura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=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= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Heat shock kn-keyword=Heat shock en-keyword=Acid stress kn-keyword=Acid stress en-keyword=dnaK kn-keyword=dnaK en-keyword=hspR kn-keyword=hspR en-keyword=groES kn-keyword=groES en-keyword=groEL kn-keyword=groEL en-keyword=Sinefungin kn-keyword=Sinefungin en-keyword=Streptomyces incarnatus kn-keyword=Streptomyces incarnatus END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=3 article-no= start-page=uuag021 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Truncation by death in the sufficient-cause framework en-subtitle= kn-subtitle= en-abstract= kn-abstract=The sufficient-cause framework has been used for decades to improve our understanding of both basic and complex causal concepts in epidemiology, such as mediation and interaction. Here, we make use of this framework to provide a description of truncation by death, in which the outcome of interest is undefined for individuals who die before the assessment time at the end of follow-up. We explain the noncausal nature of the crude estimand that compares outcomes by treatment levels conditional on observed survival by showing that it corresponds to a comparison of distinct risk-status types, which are defined based on their susceptibility to sufficient causes. Further, expressions for the crude estimand and for the survivor average causal effect (SACE)—a causal estimand defined under the principal stratification approach—are provided in terms of population-level joint frequencies of the background factors of sufficient causes. Finally, we also describe conditions, based on background factors of sufficient causes, under which the SACE is null. Our description of this problem, which studies truncation by death from a new perspective, might encourage further analyses of principal stratification-based estimands using sufficient causes. en-copyright= kn-copyright= en-aut-name=GonçalvesBronner P en-aut-sei=Gonçalves en-aut-mei=Bronner P kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoEiji en-aut-sei=Yamamoto en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Faculty of Health and Medical Sciences, University of Surrey kn-affil= affil-num=2 en-affil=Okayama University of Science kn-affil= affil-num=3 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=causal mechanisms kn-keyword=causal mechanisms en-keyword=potential outcomes kn-keyword=potential outcomes en-keyword=principal stratification kn-keyword=principal stratification en-keyword=sufficient causes kn-keyword=sufficient causes END start-ver=1.4 cd-journal=joma no-vol=93 cd-vols= no-issue=1 article-no= start-page=e00346-2 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250131 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A newly developed oral infection mouse model of shigellosis for immunogenicity and protective efficacy studies of a candidate vaccine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Shigella infection poses a significant public health challenge in the developing world. However, lack of a widely available mouse model that replicates human shigellosis creates a major bottleneck to better understanding of disease pathogenesis and development of newer drugs and vaccines. BALB/c mice pre-treated with streptomycin and iron (FeCl3) plus desferrioxamine intraperitoneally followed by oral infection with virulent Shigella flexneri 2a resulted in diarrhea, loss of body weight, bacterial colonization and progressive colitis characterized by disruption of epithelial lining, loss of crypt architecture with goblet cell depletion, increased polymorphonuclear infiltration into the mucosa, submucosal swelling (edema), and raised proinflammatory cytokines and chemokines in the large intestine. To evaluate the usefulness of the model for vaccine efficacy studies, mice were immunized intranasally with a recombinant protein vaccine containing Shigella invasion protein invasion plasmid antigen B (IpaB). Vaccinated mice conferred protection against Shigella, indicating that the model is suitable for testing of vaccine candidates. To protect both Shigella and Salmonella, a chimeric recombinant vaccine (rIpaB–T2544) was developed by fusing IpaB with Salmonella outer membrane protein T2544. Vaccinated mice developed antigen-specific serum IgG and IgA antibodies and a balanced Th1/Th2 response and were protected against oral challenge with Shigella (S. flexneri 2a, Shigella dysenteriae, and Shigella sonnei) using our present mouse model and Salmonella (Salmonella Typhi and Paratyphi) using an iron overload mouse model. We describe here the development of an oral Shigella infection model in wild-type mouse. This model was successfully used to demonstrate the immunogenicity and protective efficacy of a candidate protein subunit vaccine against Shigella. en-copyright= kn-copyright= en-aut-name=HaldarRisha en-aut-sei=Haldar en-aut-mei=Risha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HalderProlay en-aut-sei=Halder en-aut-mei=Prolay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KoleyHemanta en-aut-sei=Koley en-aut-mei=Hemanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DasSantasabuj en-aut-sei=Das en-aut-mei=Santasabuj kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of Clinical Medicine, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=2 en-affil=Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=3 en-affil=Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=4 en-affil=Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Division of Clinical Medicine, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= en-keyword=oral route kn-keyword=oral route en-keyword=S. flexneri kn-keyword=S. flexneri en-keyword=shigellosis kn-keyword=shigellosis en-keyword=bivalent subunit vaccine (IpaB–T2544) kn-keyword=bivalent subunit vaccine (IpaB–T2544) en-keyword=mouse model kn-keyword=mouse model END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=12 article-no= start-page=2058 end-page=2064 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241213 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Staphylococcus aureus δ-Toxin Induces Ca2+ Influx-Independent Degranulation of Murine Cultured Mast Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cutaneous colonization with Staphylococcus aureus (SA) is frequently observed in patients with atopic dermatitis. SA produces a wide variety of bacterial toxins, among which δ-toxin was found to induce degranulation of mast cells. Degranulation of mast cells could enhance bacterial clearance and protection from future SA infection but lead to exacerbation of atopic dermatitis. Because it remains to be determined how δ-toxin triggers degranulation, we investigated δ-toxin-induced changes in murine bone marrow-derived cultured mast cells in this study. We found that δ-toxin-induced degranulation could be classified into two phases, an early Ca2+-independent and a late Ca2+-dependent phase. Recent studies suggest that NOD-like receptor family, pyrin domain containing 3 is involved in the degranulation of mast cells, raising a possibility that leakage of K+ induced by δ-toxin is involved in the Ca2+-independent phase. However, Ca2+-independent degranulation remains unchanged although Ca2+-influx and degranulation induced by δ-toxin were significantly suppressed in the presence of high concentrations of K+. Because actin depolymerization was reported to induce degranulation in the absence of Ca2+ in the permeabilized rat peritoneal mast cells, a slow but steady decrease in the amount of filamentous actin observed here may be involved in Ca2+-independent degranulation induced by δ-toxin. Although Mas-related G protein-coupled receptor (MRGPR) X2 in humans and Mrgprb2 in mice are regarded as the receptors responsible for immunoglobulin E-independent degranulation, δ-toxin-induced degranulation remained unchanged in Mrgprb2−/− mast cells. Our findings pave the way for identification of the target receptors of δ-toxin. en-copyright= kn-copyright= en-aut-name=LiuKang en-aut-sei=Liu en-aut-mei=Kang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatayamaTomoaki en-aut-sei=Katayama en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoHitomi en-aut-sei=Sato en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Hamaoka-TamuraYuho en-aut-sei=Hamaoka-Tamura en-aut-mei=Yuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoMichiko en-aut-sei=Saito en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FurutaKazuyuki en-aut-sei=Furuta en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaSatoshi en-aut-sei=Tanaka en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Laboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University kn-affil= affil-num=2 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Laboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University kn-affil= affil-num=5 en-affil=Bioscience Research Center, Kyoto Pharmaceutical University kn-affil= affil-num=6 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Laboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University kn-affil= en-keyword=mast cell kn-keyword=mast cell en-keyword=δ-toxin kn-keyword=δ-toxin en-keyword=degranulation kn-keyword=degranulation en-keyword=inflammation kn-keyword=inflammation en-keyword=Mas-related G protein-coupled receptor kn-keyword=Mas-related G protein-coupled receptor END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=16 article-no= start-page=1886 end-page=1897 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=Methotrexate, Doxorubicin, and Cisplatin Versus Methotrexate, Doxorubicin, and Cisplatin + Ifosfamide in Poor Responders to Preoperative Chemotherapy for Newly Diagnosed High-Grade Osteosarcoma (JCOG0905): A Multicenter, Open-Label, Randomized Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Our previous NECO phase II studies on high-grade osteosarcoma suggested that administering ifosfamide (IF; 16 g/m2 [4g/m2 once on day 1, then 2g/m2 once on days 2-7] × six) to patients showing a poor response (PrRsp) to preoperative chemotherapy with methotrexate, doxorubicin, and cisplatin (MAP) improves their prognoses. In this Japan Clinical Oncology Group (JCOG) study, JCOG0905, we aimed to investigate the efficacy and safety of IF in patients with PrRsp.
Methods JCOG0905 is a multicenter, open-label, multi-institutional, randomized trial. Eligible patients (50 years and younger) had resectable, high-grade osteosarcoma (stage II or III, Union for International Cancer Control TNM) of the extremities, limb girdles, and thoracic wall. After two MAP cycles and tumor resection, patients with PrRsp were randomly assigned to either the MAP or MAP plus 15 g/m2 (3g/m2 once daily on days 1-5) × six IF (MAP + IF [MAPIF]) group. The primary end point was disease-free survival (DFS); secondary end points were overall survival (OS) and safety. The planned sample size was 100 patients with a one-sided α of .1 and a power of 0.7, assuming a 3-year DFS of 50% and 65% for MAP and MAPIF, respectively. This trial is registered with the Japan Registry of Clinical Trials (jRCT; jRCTs031180126).
Results Of the 287 patients registered between February 2010 and August 2020, 51 and 52 patients with PrRsp were assigned to the MAP and MAPIF groups, respectively. As of March 2022, DFS did not differ between groups (hazard ratio [HR], 1.05 [95% CI, 0.55 to 1.98]) and OS was numerically inferior in the MAPIF group (HR, 1.48 [95% CI, 0.68 to 3.22]). Nine and zero patients in the MAPIF and MAP groups discontinued treatment because of adverse events, respectively.
Conclusion Evidence from JCOG0905 does not support the addition of IF for patients with PrRsp. en-copyright= kn-copyright= en-aut-name=HiragaHiroaki en-aut-sei=Hiraga en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MachidaRyunosuke en-aut-sei=Machida en-aut-mei=Ryunosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaiAkira en-aut-sei=Kawai en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YonemotoTsukasa en-aut-sei=Yonemoto en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EndoMakoto en-aut-sei=Endo en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishidaYoshihiro en-aut-sei=Nishida en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NaganoAkihito en-aut-sei=Nagano en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AeKeisuke en-aut-sei=Ae en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshidaShinichirou en-aut-sei=Yoshida en-aut-mei=Shinichirou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsanumaKunihiro en-aut-sei=Asanuma en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ToguchidaJunya en-aut-sei=Toguchida en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FurutaTaisuke en-aut-sei=Furuta en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakayamaRobert en-aut-sei=Nakayama en-aut-mei=Robert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AkisueToshihiro en-aut-sei=Akisue en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HirumaToru en-aut-sei=Hiruma en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MoriiTakeshi en-aut-sei=Morii en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 ORCID= en-aut-name=HiraokaKoji en-aut-sei=Hiraoka en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakeyamaMasanobu en-aut-sei=Takeyama en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=EmoriMakoto en-aut-sei=Emori en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=TsukushiSatoshi en-aut-sei=Tsukushi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HatanoHiroshi en-aut-sei=Hatano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 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=24 ORCID= en-aut-name=IsuKazuo en-aut-sei=Isu en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=TanakaKazuhiro en-aut-sei=Tanaka en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KataokaTomoko en-aut-sei=Kataoka en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=FukudaHaruhiko en-aut-sei=Fukuda en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=IwamotoYukihide en-aut-sei=Iwamoto en-aut-mei=Yukihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 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=30 ORCID= affil-num=1 en-affil=Musculoskeletal Oncology, NHO Hokkaido Cancer Center kn-affil= affil-num=2 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=3 en-affil=Musculoskeletal Oncology, National Cancer Center Hospital kn-affil= affil-num=4 en-affil=Orthopaedic Surgery, Faculty of Medicine, Okayama University kn-affil= affil-num=5 en-affil=Orthopaedic Surgery, Chiba Cancer Center kn-affil= affil-num=6 en-affil=Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=7 en-affil=Department of Rehabilitation Medicine, Nagoya University Hospital kn-affil= affil-num=8 en-affil=Orthopaedic Surgery, Gifu University School of Medicine kn-affil= affil-num=9 en-affil=Orthopaedic Surgery, Cancer Institute Hospital kn-affil= affil-num=10 en-affil=Orthopaedic Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Orthopaedic Surgery, Mie University kn-affil= affil-num=12 en-affil=Department of Tissue Regeneration, Center for Induced Pluripotent Stem Cell Research and Application, Institute for Frontier Medical Sciences, Kyoto University kn-affil= affil-num=13 en-affil=Orthopaedic Surgery, Hiroshima University kn-affil= affil-num=14 en-affil=Department of Orthopaedic Surgery, Keio University School of Medicine kn-affil= affil-num=15 en-affil=Orthopaedic Surgery, Kobe University kn-affil= affil-num=16 en-affil=Bone and Soft Tissue Tumour Surgery, Kanagawa Cancer Center kn-affil= affil-num=17 en-affil=Orthopaedic Surgery, Kyorin University kn-affil= affil-num=18 en-affil=Orthopaedic Surgery, Kagawa University Hospital kn-affil= affil-num=19 en-affil=Orthopaedic Surgery, Kurume University Hospital kn-affil= affil-num=20 en-affil=Orthopaedic Surgery, Yokohama City University Hospital kn-affil= affil-num=21 en-affil=Orthopaedic Surgery, Sapporo Medical University Hospital kn-affil= affil-num=22 en-affil=Orthopaedic Surgery, Aichi Cancer Center kn-affil= affil-num=23 en-affil=Musculoskeletal Oncology, Niigata Cancer Center Hospital kn-affil= affil-num=24 en-affil=Orthopaedic Surgery, Niigata University Medical & Dental Hospital kn-affil= affil-num=25 en-affil=Orthopaedic Surgery, Higashi Sapporo Hospital kn-affil= affil-num=26 en-affil=Advanced Medical Sciences, Oita University Faculty of Medicine kn-affil= affil-num=27 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=28 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=29 en-affil=Orthopaedic Surgery, Kyushu Rosai Hospital kn-affil= affil-num=30 en-affil=Orthopaedic Surgery, Faculty of Medicine, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=10 article-no= start-page=1643 end-page=1652 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240809 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Radiological assessment of the dissection area in supraomohyoid neck dissection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose The current supraomohyoid neck dissection (SOHND) is performed above the omohyoid muscle to dissect levels I, II, and III in the levels of cervical lymph nodes. However, the anatomical boundary between levels III and IV is the inferior border of the cricoid cartilage. We investigated the anatomical relationship between the omohyoid muscle and cricoid cartilage using contrast-enhanced CT (CE-CT) images to assess the validity of the current SOHND.
Methods CE-CT images of the head and neck regions in patients were reviewed. The patients were divided into two groups: “malignant tumors” and “others”. The vertebral levels corresponding to the positions of anatomical structures such as the intersection of the omohyoid muscle and internal jugular vein (OM-IJ), and the inferior border of the cricoid cartilage (CC), were recorded.
Results The OM-IJ was located around the seventh cervical to the first thoracic vertebra. There was a significant difference between the malignant tumor and others groups in females (p = 0.036). The CC was located around the sixth to seventh cervical vertebrae. There was a significant sex difference in each group (malignant tumor: p < 0.0001; others: p = 0.008). Both sexes tended to have lower OM-IJ than CC, and females had significantly lower OM-IJ than males.
Conclusion This study provides clear anatomical evidence showing the difference between the SOHND dissection area and levels I, II, and III. It could be considered that in most cases SOHND invades level IV, not just levels I, II, and III, especially in female patients. en-copyright= kn-copyright= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhyamaYoshio en-aut-sei=Ohyama en-aut-mei=Yoshio 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= en-aut-name=MatsushitaYuki en-aut-sei=Matsushita en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TubbsR. Shane en-aut-sei=Tubbs en-aut-mei=R. Shane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KitagawaNorio en-aut-sei=Kitagawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawazuToshiyuki en-aut-sei=Kawazu en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HisatomiMiki en-aut-sei=Hisatomi en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=FujikuraMamiko en-aut-sei=Fujikura en-aut-mei=Mamiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AsaumiJunichi en-aut-sei=Asaumi en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Clinical Anatomy Research Association in Oral and Maxillofacial Surgery kn-affil= affil-num=3 en-affil=Clinical Anatomy Research Association in Oral and Maxillofacial Surgery 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=Clinical Anatomy Research Association in Oral and Maxillofacial Surgery kn-affil= affil-num=6 en-affil=Clinical Anatomy Research Association in Oral and Maxillofacial Surgery kn-affil= affil-num=7 en-affil=Clinical Anatomy Research Association in Oral and Maxillofacial Surgery kn-affil= affil-num=8 en-affil= kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Anatomy kn-keyword=Anatomy en-keyword=Omohyoid muscle kn-keyword=Omohyoid muscle en-keyword=Computed tomography kn-keyword=Computed tomography en-keyword=Neck dissection kn-keyword=Neck dissection en-keyword=Vertebra kn-keyword=Vertebra en-keyword=Cancer kn-keyword=Cancer END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue=5 article-no= start-page=upaf091 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Highly emissive and robust diarylethene fluorophore incorporating imide-fused phenanthryl moieties en-subtitle= kn-subtitle= en-abstract= kn-abstract=The fluorescence properties and photostabilities of (E)-diarylethenes (DPEs), featuring two 3-phenanthryl moieties, were investigated. Pristine (E)-di-1,2-(3-phenanthryl)ethene and its ester derivative, respectively referred to as DPE-H and DPE-E, exhibited blue fluorescence. However, they underwent a two-step photoreaction sequence that yielded [7]helicenes, resulting in a gradual reduction of the fluorescence intensity. In contrast, the imide-fused derivative DPE-I displayed intense green fluorescence and it was unexpectedly photostable in solution, maintaining its highly efficient fluorescent nature even after prolonged light exposure. DPE-I, thus, provides a new type of highly efficient and robust diarylethene fluorophore. en-copyright= kn-copyright= en-aut-name=NoseKeito en-aut-sei=Nose en-aut-mei=Keito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamajiMinoru en-aut-sei=Yamaji en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriTadashi en-aut-sei=Mori en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniFumito en-aut-sei=Tani en-aut-mei=Fumito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotoKenta en-aut-sei=Goto en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Program of Applied Chemistry, Cluster of Materials and Environment, Gunma University kn-affil= affil-num=3 en-affil=Research Center for Environmental Preservation and Graduate School of Engineering, The University of Osaka kn-affil= affil-num=4 en-affil=Institute for Materials Chemistry and Engineering, Kyushu University kn-affil= affil-num=5 en-affil=Institute for Materials Chemistry and Engineering, Kyushu University kn-affil= affil-num=6 en-affil=Department of Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=diarylethene kn-keyword=diarylethene en-keyword=fluorescence kn-keyword=fluorescence en-keyword=phenanthreneimide kn-keyword=phenanthreneimide END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=2 article-no= start-page=18 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250418 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The effect of Fe incorporation on the single-crystal elasticity of δ-AlOOH en-subtitle= kn-subtitle= en-abstract= kn-abstract=The seismic mapping of hydrous materials in the Earth’s deep interior requires experimental constraints on the elastic anisotropy of hydrous minerals and phases. Oxyhydroxides like δ-(Al,Fe)OOH are arguably the main hosts of water in the lower mantle. Therefore, constraints on the single-crystal elastic tensor of δ-(Al,Fe)OOH solid solutions are crucial to quantify the elastic anisotropy of this material, and advance the current understanding of the recycling of water into the lower mantle. Yet, experimental data for intermediate compositions are scarce, limiting the understanding of how Fe incorporation affects the single-crystal elastic properties of δ-AlOOH. In this study, we provide experimental constraints on the single-crystal elasticity of two δ-(Al,Fe)OOH solid solutions, with Fe/(Al + Fe) of 0.06(1) and 0.133(3). Large single-crystal samples of δ-(Al,Fe)OOH were synthetized at high pressures and temperatures using a multi-anvil press, and the full elastic stiffness tensors were determined at ambient conditions by combining X-ray diffraction and Brillouin scattering measurements. We show that replacing Al3+ with Fe3+ in δ-(Al,Fe)OOH lowers the magnitude of most coefficients of the elastic stiffness tensor (cij), which translates into a substantial reduction of aggregate moduli and acoustic wave velocities. We further show that, at ambient conditions, the acoustic anisotropy of δ-(Al,Fe)OOH displays no sensitivity to Fe–Al substitution. en-copyright= kn-copyright= en-aut-name=SattaNiccolò en-aut-sei=Satta en-aut-mei=Niccolò kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=CrinitiGiacomo en-aut-sei=Criniti en-aut-mei=Giacomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Boffa BallaranTiziana en-aut-sei=Boffa Ballaran en-aut-mei=Tiziana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KurnosovAlexander en-aut-sei=Kurnosov en-aut-mei=Alexander kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BuchenJohannes en-aut-sei=Buchen en-aut-mei=Johannes kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MarquardtHauke en-aut-sei=Marquardt en-aut-mei=Hauke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Institut für Mineralogie, Universität Münster kn-affil= affil-num=2 en-affil=Bayerisches Geoinstitut, Universität Bayreuth kn-affil= affil-num=3 en-affil=Bayerisches Geoinstitut, Universität Bayreuth kn-affil= affil-num=4 en-affil=Bayerisches Geoinstitut, Universität Bayreuth kn-affil= affil-num=5 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=6 en-affil=Bayerisches Geoinstitut, Universität Bayreuth kn-affil= affil-num=7 en-affil=Department of Earth Sciences, University of Oxford kn-affil= en-keyword=Elasticity kn-keyword=Elasticity en-keyword=δ-AlOOH kn-keyword=δ-AlOOH en-keyword=Water kn-keyword=Water en-keyword=Anisotropy kn-keyword=Anisotropy en-keyword=Solid solutions kn-keyword=Solid solutions en-keyword=Brillouin scattering kn-keyword=Brillouin scattering END start-ver=1.4 cd-journal=joma no-vol=361 cd-vols= no-issue= article-no= start-page=107331 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of chemistry on the compressibility and high-pressure structural evolution of the CaFe2O4-type aluminous silicate phase en-subtitle= kn-subtitle= en-abstract= kn-abstract=Approximately 22–26 vol% of a basaltic phase assemblage at lower mantle conditions is comprised of a (Na,Mg,Fe2+)(Al,Si,Fe3+)2O4 phase with CaFe2O4-type (CF-type) structure. Previous experimental studies attempted to determine the equation of state of the CF-type phase but reported contrasting compressibility values, even for samples with the same composition. Therefore, the elastic properties of the CF-type phase remain, to date, largely unconstrained. Here, we conducted single-crystal X-ray diffraction (SCXRD) measurements in the diamond anvil cell (DAC) at high pressure and room temperature on three samples of CF-type phase with compositions Na0.90(1)Al1.03(2)Si1.00(2)O4 (NaCF), Na0.66(4)Mg0.28(4)Al1.22(3)Si0.78(3)O4 (MgCF) and Na0.62(2)Mg0.19(1)Fe2+0.17(1)Fe3+0.080(4)Al1.20(3)Si0.70(1)O4 (FeCF). A multi-sample loading approach was employed for most DAC runs, where two samples were loaded in the same sample chamber to reduce possible systematic deviations between datasets, thus enhancing internal consistency and corroborating data reproducibility. Experiments on the NaCF and MgCF samples were conducted up to ∼50 GPa, while the FeCF sample was compressed to ∼72 GPa to better characterize the effect of the spin crossover of octahedrally coordinated Fe3+. We found the isothermal bulk modulus (KT0) to increase with decreasing NaAlSiO4 content, accompanied by only a slight decrease in its pressure derivative (K'T0). Analysis of the crystal structures of the three samples at high pressure allowed compositional trends to be determined also for the interatomic bonds and polyhedral compressibility, as well as the distortion indices. These suggest an overall stiffening of the A site with increasing Mg2+ and Fe2+ content, as well of the two B sites with increasing Al3+ and Fe3+ content. Enhanced compressibility of the unit cell and octahedral B sites was observed between ∼26–42 GPa in the FeCF sample, suggesting a pressure-induced spin crossover of Fe3+, in agreement with some previous observations. Finally, trends in the elastic properties from experimental studies conducted along the NaAlSiO4-MgAl2O4 join are discussed and used as a proxy to evaluate the reliability of end-member properties for the CF-type phase employed in most recent mineral physical and thermodynamic databases. Our analysis suggests current mineral physical models might underestimate densities and overestimate bulk sound velocities of NaAlSiO4-rich CF-type phases with basaltic composition. en-copyright= kn-copyright= en-aut-name=CrinitiGiacomo en-aut-sei=Criniti en-aut-mei=Giacomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Boffa BallaranTiziana en-aut-sei=Boffa Ballaran en-aut-mei=Tiziana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurnosovAlexander en-aut-sei=Kurnosov en-aut-mei=Alexander 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= en-aut-name=RogmannElena-Marie en-aut-sei=Rogmann en-aut-mei=Elena-Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GlazyrinKonstantin en-aut-sei=Glazyrin en-aut-mei=Konstantin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FedotenkoTimofey en-aut-sei=Fedotenko en-aut-mei=Timofey kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FrostDaniel J. en-aut-sei=Frost en-aut-mei=Daniel J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=2 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=3 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=4 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=5 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=6 en-affil=Deutsches Elektronen-Synchrotron DESY kn-affil= affil-num=7 en-affil=Deutsches Elektronen-Synchrotron DESY kn-affil= affil-num=8 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= en-keyword=CaFe2O4-type phase kn-keyword=CaFe2O4-type phase en-keyword=Lower mantle kn-keyword=Lower mantle en-keyword=Equations of state kn-keyword=Equations of state en-keyword=Structural refinements kn-keyword=Structural refinements en-keyword=Crystal chemistry kn-keyword=Crystal chemistry en-keyword=Fe3+ spin-crossover kn-keyword=Fe3+ spin-crossover END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=3 article-no= start-page=497 end-page=503 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Five-year outcomes with gefitinib induction and chemoradiotherapy in EGFR-mutant stage III non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background We previously showed the 2-year OS rate, the primary endpoint, of 90% in a phase II trial of gefitinib induction followed by chemoradiotherapy (CRT) in unresectable, stage III, EGFR-mutant, non-small-cell lung cancer (NSCLC). However, neither long-term survival data nor late-phase adverse event profiles have been presented.
Patients and methods Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy for 8 weeks. After confirming no disease progression during induction therapy, cisplatin and docetaxel on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy were subsequently administered.
Results In the enrolled twenty patients, the 5-year OS rate and median survival time were 70.0% [95% confidence interval: 45.1–85.3] and 5.5 years [4.91-NE], respectively, whereas 5-year PFS rate and median PFS time were 15.0% (3.7–33.5) and 1.4 years [0.69–2.29], respectively. Efficacy did not seem influenced even if radiation field was re-planed in response to the effect of gefitinib induction. As for late adverse events, pulmonary fibrosis occurred in 7 patients (35%). The median time from completion of CRT to the occurrence of the event was 245 days. All were grade 1, and there was no evidence of cavitation of the lesions or chronic infections such as Aspergillus infection during the course of the disease. One case of small cell lung cancer occurred during the period.
Conclusions With longer follow-up time, we demonstrated favorable efficacy with tolerable toxicity profiles in the EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III, NSCLC.
Trial registration numbers UMIN00005086. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000006047&type=summary&language=EjRCTs071180036. https://jrct.niph.go.jp/latest-detail/jRCTs071180036 en-copyright= kn-copyright= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaekiSho en-aut-sei=Saeki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakataShinya en-aut-sei=Sakata en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamaguchiMasafumi en-aut-sei=Yamaguchi en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaradaDaijiro en-aut-sei=Harada en-aut-mei=Daijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BesshoAkihiro en-aut-sei=Bessho en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaKentaro en-aut-sei=Tanaka en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= en-aut-name=GembaKenichi en-aut-sei=Gemba en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=SatoAkiko en-aut-sei=Sato en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 ORCID= en-aut-name=KishimotoJunji en-aut-sei=Kishimoto en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShioyamaYoshiyuki en-aut-sei=Shioyama en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KatsuiKuniaki en-aut-sei=Katsui en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SugioKenji en-aut-sei=Sugio en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Kumamoto University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Kumamoto University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic Oncology, NHO Kyushu Cancer Center kn-affil= affil-num=5 en-affil=Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Kyushu University Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Kitakyushu Municipal Medical Center kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Chugoku Central 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=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=16 en-affil=Radiation Oncology, Ion Beam Therapy Center, SAGA HIMAT Foundation kn-affil= affil-num=17 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=18 en-affil=Division of Radiation Oncology, Department of Thoracic and Breast Surgery, Oita University kn-affil= affil-num=19 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=Non-small-cell lung cancer kn-keyword=Non-small-cell lung cancer en-keyword=Locally advanced setting kn-keyword=Locally advanced setting en-keyword=Chemoradiation kn-keyword=Chemoradiation en-keyword=Epidermal growth factor receptor kn-keyword=Epidermal growth factor receptor END start-ver=1.4 cd-journal=joma no-vol=134 cd-vols= no-issue=24 article-no= start-page=245001 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250616 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Acceleration of Positive Muons by a Radio-Frequency Cavity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Acceleration of positive muons from thermal energy to 100 keV has been demonstrated. Thermal muons were generated by resonant multiphoton ionization of muonium atoms emitted from a sheet of laser-ablated aerogel. The thermal muons were first electrostatically accelerated to 5.7 keV, followed by further acceleration to 100 keV using a radio-frequency quadrupole with an intensity of 2×10−3  𝜇+/pulse. The transverse normalized rms emittance of the accelerated muons in the horizontal and vertical planes were 0.85±0.25⁢(s⁢t⁢a⁢t)+0.22−0.13⁢(syst)   ⁢𝜋 mm mrad and 0.32±0.03⁢(stat)+0.05−0.02⁢(syst)   𝜋 mm mrad, respectively. The measured emittance values demonstrated phase-space reduction by a factor of 2.0 ×102 (horizontal) and 4.1 ×102 (vertical) allowing good acceleration efficiency. These results pave the way to realize the first-ever muon accelerator for a variety of applications in particle physics, material science, and other fields. en-copyright= kn-copyright= en-aut-name=AritomeS. en-aut-sei=Aritome en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FutatsukawaK. en-aut-sei=Futatsukawa en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaraH. en-aut-sei=Hara en-aut-mei=H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HayasakaK. en-aut-sei=Hayasaka en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IbarakiY. en-aut-sei=Ibaraki en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IchikawaT. en-aut-sei=Ichikawa en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IijimaT. en-aut-sei=Iijima en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IinumaH. en-aut-sei=Iinuma en-aut-mei=H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IkedoY. en-aut-sei=Ikedo en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ImaiY. en-aut-sei=Imai en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=InamiK. en-aut-sei=Inami en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IshidaK. en-aut-sei=Ishida en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KamalS. en-aut-sei=Kamal en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KamiokaS. en-aut-sei=Kamioka en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KawamuraN. en-aut-sei=Kawamura en-aut-mei=N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KimuraM. en-aut-sei=Kimura en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KodaA. en-aut-sei=Koda en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KojiS. en-aut-sei=Koji en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KojimaK. en-aut-sei=Kojima en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KondoA. en-aut-sei=Kondo en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KondoY. en-aut-sei=Kondo en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KuzubaM. en-aut-sei=Kuzuba en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MatsushitaR. en-aut-sei=Matsushita en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MibeT. en-aut-sei=Mibe en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=MiyamotoY. en-aut-sei=Miyamoto en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=NakamuraJ. G. en-aut-sei=Nakamura en-aut-mei=J. G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=NakazawaY. en-aut-sei=Nakazawa en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=OgawaS. en-aut-sei=Ogawa en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=OkazakiY. en-aut-sei=Okazaki en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=OlinA. en-aut-sei=Olin en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=OtaniM. en-aut-sei=Otani en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=OyamaS. en-aut-sei=Oyama en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=SaitoN. en-aut-sei=Saito en-aut-mei=N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=SatoH. en-aut-sei=Sato en-aut-mei=H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=SatoT. en-aut-sei=Sato en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=SatoY. en-aut-sei=Sato en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=ShimomuraK. en-aut-sei=Shimomura en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=ShioyaZ. en-aut-sei=Shioya en-aut-mei=Z. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=StrasserP. en-aut-sei=Strasser en-aut-mei=P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=SugiyamaS. en-aut-sei=Sugiyama en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=SumiK. en-aut-sei=Sumi en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=SuzukiK. en-aut-sei=Suzuki en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=TakeuchiY. en-aut-sei=Takeuchi en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=TanidaM. en-aut-sei=Tanida en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=TojoJ. en-aut-sei=Tojo en-aut-mei=J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=UedaK. en-aut-sei=Ueda en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=UetakeS. en-aut-sei=Uetake en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=XieX. H. en-aut-sei=Xie en-aut-mei=X. H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=YamadaM. en-aut-sei=Yamada en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=YamamotoS. en-aut-sei=Yamamoto en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=YamazakiT. en-aut-sei=Yamazaki en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=YamuraK. en-aut-sei=Yamura en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=YoshidaM. en-aut-sei=Yoshida en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=YoshiokaT. en-aut-sei=Yoshioka en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=YotsuzukaM. en-aut-sei=Yotsuzuka en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= affil-num=1 en-affil=Graduate School of Science, University of Tokyo kn-affil= affil-num=2 en-affil=High Energy Accelerator Research Organization kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=Institute of Science and Technology, Niigata University kn-affil= affil-num=5 en-affil=Graduate School of Science, Nagoya University kn-affil= affil-num=6 en-affil=Graduate School of Science, Nagoya University kn-affil= affil-num=7 en-affil=Graduate School of Science, Nagoya University kn-affil= affil-num=8 en-affil=Graduate School of Science and Engineering, Ibaraki University kn-affil= affil-num=9 en-affil=High Energy Accelerator Research Organization 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, Nagoya University kn-affil= affil-num=12 en-affil=High Energy Accelerator Research Organization kn-affil= affil-num=13 en-affil=Department of Chemistry, Laboratory for Advanced Spectroscopy and Imaging Research (LASIR), University of British Columbia kn-affil= affil-num=14 en-affil=High Energy Accelerator Research Organization kn-affil= affil-num=15 en-affil=High Energy Accelerator Research Organization kn-affil= affil-num=16 en-affil=High Energy Accelerator Research Organization kn-affil= affil-num=17 en-affil=High Energy Accelerator Research Organization kn-affil= affil-num=18 en-affil=Graduate School of Science, Nagoya University kn-affil= affil-num=19 en-affil=Kobayashi-Maskawa Institute for the Origin of Particles and the Universe, Nagoya University kn-affil= affil-num=20 en-affil=Graduate School of Science, Nagoya University kn-affil= affil-num=21 en-affil=Japan Atomic Energy Agency (JAEA) kn-affil= affil-num=22 en-affil=Graduate School of Science and Engineering, Ibaraki University kn-affil= affil-num=23 en-affil=Graduate School of Science, University of Tokyo kn-affil= affil-num=24 en-affil=High Energy Accelerator Research Organization kn-affil= affil-num=25 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=26 en-affil=High Energy Accelerator Research Organization kn-affil= affil-num=27 en-affil=Graduate School of Science and Engineering, Ibaraki University kn-affil= affil-num=28 en-affil=Research Center of Advanced Particle Physics, Kyushu University kn-affil= affil-num=29 en-affil=High Energy Accelerator Research Organization kn-affil= affil-num=30 en-affil=Department of Physics and Astronomy, University of Victoria kn-affil= affil-num=31 en-affil=High Energy Accelerator Research Organization kn-affil= affil-num=32 en-affil=Graduate School of Science, University of Tokyo kn-affil= affil-num=33 en-affil=High Energy Accelerator Research Organization kn-affil= affil-num=34 en-affil=Graduate School of Science and Engineering, Ibaraki University kn-affil= affil-num=35 en-affil=Graduate School of Science, University of Tokyo kn-affil= affil-num=36 en-affil=Institute of Science and Technology, Niigata University kn-affil= affil-num=37 en-affil=High Energy Accelerator Research Organization kn-affil= affil-num=38 en-affil=Faculty of Science, Kyushu University kn-affil= affil-num=39 en-affil=High Energy Accelerator Research Organization kn-affil= affil-num=40 en-affil=Graduate School of Science, Nagoya University kn-affil= affil-num=41 en-affil=Graduate School of Science, Nagoya University kn-affil= affil-num=42 en-affil=Kobayashi-Maskawa Institute for the Origin of Particles and the Universe, Nagoya University kn-affil= affil-num=43 en-affil=Faculty of Science, Kyushu University kn-affil= affil-num=44 en-affil=Faculty of Science, Kyushu University kn-affil= affil-num=45 en-affil=Faculty of Science, Kyushu University kn-affil= affil-num=46 en-affil=Graduate School of Science, Nagoya University, Nagoya kn-affil= affil-num=47 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=48 en-affil=School of Physics, Peking University kn-affil= affil-num=49 en-affil=Faculty of Science, Kyushu University kn-affil= affil-num=50 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=51 en-affil=High Energy Accelerator Research Organization kn-affil= affil-num=52 en-affil=Institute of Science and Technology, Niigata University kn-affil= affil-num=53 en-affil=High Energy Accelerator Research Organization kn-affil= affil-num=54 en-affil=Research Center of Advanced Particle Physics, Kyushu University kn-affil= affil-num=55 en-affil=Graduate School of Science, Nagoya University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=1 article-no= start-page=89 end-page=111 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=Retract problem and a subset admitting complete Boolean algebra structure of monoidally distributive posets en-subtitle= kn-subtitle= en-abstract= kn-abstract=In [3], Hovey and Palmieri proved many interesing results around the Bousfield lattice of the stable homotopy caregory of spectra. In [4], the author, Shimomura and Tatehara defined monoidally distributive posets as a generalization of the Bousfield lattice. In this paper, we consider the retract problem and a subset admitting complete Boolean algebra structure of monoidally distributive posets. In the last section, we see that some results in [3] are given by our results in this paper. en-copyright= kn-copyright= en-aut-name=KatoRyo en-aut-sei=Kato en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Core Studies, Kochi University of Technology kn-affil= en-keyword=Bousfield lattice kn-keyword=Bousfield lattice en-keyword=Monoidal poset kn-keyword=Monoidal poset en-keyword=Retract problem kn-keyword=Retract problem END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=1 article-no= start-page=63 end-page=75 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=The Dijkgraaf-Witten invariants from second Chern classes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Given a 3-cocycle ψ in the cohomology of a finite group G, we can define the Dijkgraaf-Witten invariant of closed 3-manifolds. In this paper, we focus on the case where ψ is a 3-cocycle systematically transferred from the second Chern class of a complex representation of G, and show some procedures for computing the invariant, and clarify its topological interpretation under some conditions. en-copyright= kn-copyright= en-aut-name=NosakaTakefumi en-aut-sei=Nosaka en-aut-mei=Takefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Mathematics, Tokyo Institute of Technology kn-affil= en-keyword=Group cohomology kn-keyword=Group cohomology en-keyword=3-manifold kn-keyword=3-manifold en-keyword=Chern classes kn-keyword=Chern classes en-keyword=splitting principle kn-keyword=splitting principle END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=10 article-no= start-page=1421 end-page=1430 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260515 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mycobacterium intracellulare Infection in a Japanese Patient with Signal Transducer and Activator of Transcription-3 Gain-of-function Syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Signal transducer and activator of transcription-3 (STAT3) gain-of-function (GOF) syndrome predisposes patients to autoimmunity diseases. Yet, nontuberculous mycobacterial (NTM) infections have rarely been described. We herein report a teenage Japanese patient with genetically confirmed STAT3-GOF syndrome who developed Mycobacterium intracellulare disease. Combination antimycobacterial chemotherapy reduced the bacterial burden; however, the refractory NTM infection relapsed after initiation of adjunctive tofacitinib therapy. The present case demonstrates that host-directed therapy must be combined with prolonged antimycobacterial regimens to control drug-resistant NTM in patients with inborn errors of immunity. en-copyright= kn-copyright= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SoejimaYoshiaki en-aut-sei=Soejima en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokumasuKazuki en-aut-sei=Tokumasu en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiraiYoji en-aut-sei=Hirai en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawaguchiMarina en-aut-sei=Kawaguchi en-aut-mei=Marina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=NakamotoKenta en-aut-sei=Nakamoto en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UdaKazuhiro en-aut-sei=Uda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=HasegawaKousei en-aut-sei=Hasegawa en-aut-mei=Kousei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=14 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=inborn errors of immunity kn-keyword=inborn errors of immunity en-keyword=Mycobacterium avium complex kn-keyword=Mycobacterium avium complex en-keyword=nontuberculous mycobacteria kn-keyword=nontuberculous mycobacteria en-keyword=primary immunodeficiency syndrome kn-keyword=primary immunodeficiency syndrome en-keyword=signal transducer and activator of transcription-3 kn-keyword=signal transducer and activator of transcription-3 END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue=5 article-no= start-page=1142 end-page=1155.e6 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=Compound starch granule formation in grass seeds is associated with distinct temporal patterns of gene expression en-subtitle= kn-subtitle= en-abstract= kn-abstract=There is extensive interspecies variation in starch granule morphology in the endosperm of grass species, but the factors underpinning this variation are poorly understood. The two major granule morphology types among species are simple and compound granules, where simple granules arise from a single initiation per amyloplast, and compound granules form from multiple granule initiations. Here, we carried out an extensive survey of seed starch morphology, examining specimens from 105 species within the Pooideae using electron microscopy. This not only expanded our current knowledge of the diversity of starch granule types but also confirmed the homoplasy of simple and compound starch granules. We then selected species representing independent origins of simple (Brachyelytrum japonicum, Phaenosperma globosa, and Brachypodium distachyon) and compound granules (Nardus stricta, Melica altissima, and Calamagrostis brachytricha) for analysis of starch structure and gene expression. There were no clear patterns in starch content, amylopectin structure, or amylose content that could distinguish the two granule types. However, comparative transcriptomics over seed development revealed gene expression patterns associated with granule type, most notably increasing expression of STARCH SYNTHASE 3a (SS3a), STARCH BRANCHING ENZYME 1 (SBE1), and limit dextrinases (LDAs) between 3 and 9 days post anthesis in species with compound granules. Mutation of these genes in rice, which natively produces compound granules, resulted in altered granule shape and/or size. Our work highlights differences in gene expression that could contribute to natural variation in granule morphology within the Pooideae while providing important new starch phenotype and gene expression datasets that can be widely used to study endosperm development. en-copyright= kn-copyright= en-aut-name=Watson-LazowskiAlexander en-aut-sei=Watson-Lazowski en-aut-mei=Alexander kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FeikeDoreen en-aut-sei=Feike en-aut-mei=Doreen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NgaiQi Yang en-aut-sei=Ngai en-aut-mei=Qi Yang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EschLara en-aut-sei=Esch en-aut-mei=Lara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujitaNaoko en-aut-sei=Fujita en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsushimaRyo en-aut-sei=Matsushima en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SmithAlison M. en-aut-sei=Smith en-aut-mei=Alison M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SeungDavid en-aut-sei=Seung en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=John Innes Centre, Norwich Research Park kn-affil= affil-num=2 en-affil=John Innes Centre, Norwich Research Park kn-affil= affil-num=3 en-affil=John Innes Centre, Norwich Research Park kn-affil= affil-num=4 en-affil=John Innes Centre, Norwich Research Park kn-affil= affil-num=5 en-affil=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=John Innes Centre, Norwich Research Park kn-affil= affil-num=8 en-affil=John Innes Centre, Norwich Research Park kn-affil= en-keyword=amylopectin kn-keyword=amylopectin en-keyword=amylose kn-keyword=amylose en-keyword=endosperm kn-keyword=endosperm en-keyword=grasses kn-keyword=grasses en-keyword=starch kn-keyword=starch en-keyword=starch granule kn-keyword=starch granule en-keyword=transcriptomics kn-keyword=transcriptomics END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=524 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250322 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-term outcomes of salvage high-dose-rate brachytherapy for localized recurrence of prostate cancer following definitive radiation therapy: a retrospective analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Salvage high-dose-rate brachytherapy (HDR-BT) is a potential treatment for localized recurrence of prostate cancer following definitive radiation therapy. This study aimed to evaluate the long-term safety and efficacy of HDR-BT alone, without androgen deprivation therapy (ADT), in this patient population.
Methods We conducted a retrospective analysis of patients with prostate cancer who developed pathologically confirmed local recurrence after definitive radiation therapy and were treated with salvage HDR-BT alone at Kawasaki Medical School Hospital between 2007 and 2021. The prescribed HDR-BT dose was 22 Gy in 2 fractions. Biochemical relapse-free survival (bRFS), cause-specific survival (CSS), and overall survival (OS) were assessed using the Kaplan–Meier method. Adverse events were evaluated based on the Common Terminology Criteria for Adverse Events.
Results Thirty-five patients were included, with a median follow-up of 66.0 months (range, 8.1–169.1). The 5-year bRFS, CSS, and OS rates were 29.7%, 100%, and 89.3%, respectively. Biochemical recurrence occurred in 21 patients (60.0%). Grade 2 adverse events were reported in eight patients (22.9%), while two (5.7%) experienced grade 3 adverse events. All grade 3 adverse events occurred in patients who had HDR-BT as their initial definitive radiation therapy.
Conclusions Salvage HDR-BT without ADT is a safe and effective treatment option for localized prostate cancer recurrence after definitive radiation therapy. It provides excellent CSS rates with acceptable toxicity while potentially reducing the need for ADT. Further prospective studies are warranted to confirm these findings. en-copyright= kn-copyright= en-aut-name=WatanabeKenta en-aut-sei=Watanabe en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KamitaniNobuhiko en-aut-sei=Kamitani en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkedaNaoki en-aut-sei=Ikeda en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawataYujiro en-aut-sei=Kawata en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TokiyaRyoji en-aut-sei=Tokiya en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HayashiTakafumi en-aut-sei=Hayashi en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyajiYoshiyuki en-aut-sei=Miyaji en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TamadaTsutomu en-aut-sei=Tamada en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatsuiKuniaki en-aut-sei=Katsui en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Urology, Kawasaki Medical School kn-affil= affil-num=8 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=9 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= en-keyword=Prostate cancer kn-keyword=Prostate cancer en-keyword=Radiation therapy kn-keyword=Radiation therapy en-keyword=High kn-keyword=High en-keyword=Dose kn-keyword=Dose en-keyword=Rate brachytherapy kn-keyword=Rate brachytherapy en-keyword=Salvage therapy kn-keyword=Salvage therapy en-keyword=Biochemical recurrence kn-keyword=Biochemical recurrence en-keyword=Local recurrence kn-keyword=Local recurrence en-keyword=Androgen deprivation therapy kn-keyword=Androgen deprivation therapy en-keyword=Long kn-keyword=Long en-keyword=Term outcomes kn-keyword=Term outcomes en-keyword=Toxicity kn-keyword=Toxicity en-keyword=Cause kn-keyword=Cause en-keyword=Specific survival kn-keyword=Specific survival END start-ver=1.4 cd-journal=joma no-vol=301 cd-vols= no-issue=3 article-no= start-page=108273 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Taste receptor type 1 member 3 in osteoclasts regulates osteoclastogenesis via detection of glucose en-subtitle= kn-subtitle= en-abstract= kn-abstract=The taste system extends beyond the oral cavity, with various taste receptors found in extraoral organs. Mice deficient in the taste receptor type 1 (TAS1R) family member, TAS1R3, and fed a high-fat, high-sugar diet showed high bone mass without altering food consumption. However, the underlying mechanisms, including the cell types responsible for TAS1R3 expression, remain unclear. Here, we demonstrate the expression and function of TAS1R3 in osteoclasts, which are responsible for bone resorption. The expression of Tas1r3, but not Tas1r1 or Tas1r2, is evoked during osteoclast differentiation. Osteoclastogenesis-related genes were downregulated in TAS1R3-deficient mice, whereas the opposite phenotypes were elicited by TAS1R3 overexpression. Contrary to the common heterodimerization with TAS1R1 or TAS1R2, TAS1R3 formed a homodimer that functioned to detect glucose, enhance p38 phosphorylation, and induce osteoclastogenesis. These results provide novel insights into the role of TAS1R3 in bone metabolism and suggest that TAS1R3 may be a viable target for therapeutic agents in bone metabolic diseases. en-copyright= kn-copyright= en-aut-name=YoshimuraAnna en-aut-sei=Yoshimura en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsubaraTakuma en-aut-sei=Matsubara en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KodamaNao en-aut-sei=Kodama en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KakutaYoshimitsu en-aut-sei=Kakuta en-aut-mei=Yoshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YasudaKazuma en-aut-sei=Yasuda en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KaminumaOsamu en-aut-sei=Kaminuma en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HosomiShuhei en-aut-sei=Hosomi en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShinkawaHiroji en-aut-sei=Shinkawa en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YuanQuan en-aut-sei=Yuan en-aut-mei=Quan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawamotoTatsuo en-aut-sei=Kawamoto en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KokabuShoichiro en-aut-sei=Kokabu en-aut-mei=Shoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Division of Molecular Signaling and Biochemistry, Kyushu Dental University kn-affil= affil-num=2 en-affil=Division of Molecular Signaling and Biochemistry, Kyushu Dental University kn-affil= affil-num=3 en-affil=Division of Molecular Signaling and Biochemistry, Kyushu Dental University kn-affil= affil-num=4 en-affil=Laboratory of Structural Biology, Graduate School of Systems Life Sciences, Kyushu University kn-affil= affil-num=5 en-affil=Division of Molecular Signaling and Biochemistry, Kyushu Dental University kn-affil= affil-num=6 en-affil=Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Disease Model, Research Institute of Radiation Biology and Medicine, Hiroshima University kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=9 en-affil=Department of Hepatobiliary-Pancreatic Surgery, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=10 en-affil=State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University kn-affil= affil-num=11 en-affil=Division of Orofacial Functions and Orthodontics, Kyushu Dental University kn-affil= affil-num=12 en-affil=Division of Molecular Signaling and Biochemistry, Kyushu Dental University kn-affil= en-keyword=glucose kn-keyword=glucose en-keyword=osteoclasts kn-keyword=osteoclasts en-keyword=p38 kn-keyword=p38 en-keyword=TAS1R3 kn-keyword=TAS1R3 en-keyword=taste receptor kn-keyword=taste receptor END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=14404 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260217 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Boulder populations and orientation trends on asteroid Ryugu: implications for rubble-pile surface processes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Asteroid (162173) Ryugu is a spinning-top shaped, rubble-pile C-type asteroid with a surface dominated by boulders spanning a broad size-range. Using Hayabusa2 ONC-T mosaics for mapping, we present the most extensive global boulder dataset to date, representing an eleven-fold increase over the earliest survey and greater completeness than later AI-based estimates. Crucially, this work provides the first global boulder orientation dataset. The cumulative size-frequency distribution follows a power-law slope of − 2.665 ± 0.066 (boulders ≥ 3 m), indicating its fragmented nature. Boulder density is lower along the equatorial ridge, consistent with regolith accumulation during earlier YORP-driven spin-up and poleward migration of blocks during the present spin-down phase. Orientation analyses reveal systematic hemispheric trends in what we define as slope-breaker zones (i.e., regions of high slope differentials), with NW–SE alignment in the northern hemisphere and NE–SW in the southern hemisphere, but absent at the equatorial ridge and poles. We interpret these as reorientations that developed during downslope boulder migration, as despite ongoing spin-down, the current spin rate remains high enough to drive such motion. In addition, fresh craters exhibit locally heightened boulder densities, recording ongoing resurfacing by impact events that exhume buried subsurface boulders and segregate them from finer regolith via seismic shaking induced granular convection. Together, these results yield new insights into rubble-pile surface evolution, rotational dynamics, and impact-driven resurfacing, with boulder orientations providing critical evidence of spin-related downslope transport and establish a framework for comparative asteroid studies. en-copyright= kn-copyright= en-aut-name=RayAditya en-aut-sei=Ray en-aut-mei=Aditya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=VincentLisa M. en-aut-sei=Vincent en-aut-mei=Lisa M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuchiHiroshi en-aut-sei=Kikuchi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HemmiRyodo en-aut-sei=Hemmi en-aut-mei=Ryodo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OrmöJens en-aut-sei=Ormö en-aut-mei=Jens kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=International Research School of Planetary Sciences, Università G. d‘Annunzio kn-affil= affil-num=4 en-affil=Department of Earth Sciences, Utrecht University kn-affil= affil-num=5 en-affil=Gakushuin University kn-affil= affil-num=6 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=7 en-affil=Centro de Astrobiología (CAB), CSIC-INTA kn-affil= en-keyword=Asteroid Ryugu kn-keyword=Asteroid Ryugu en-keyword=Asteroidal surfaces kn-keyword=Asteroidal surfaces en-keyword=Regolith kn-keyword=Regolith en-keyword=Geological processes kn-keyword=Geological processes en-keyword=Impact processes kn-keyword=Impact processes END start-ver=1.4 cd-journal=joma no-vol=207 cd-vols= no-issue= article-no= start-page=106961 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=Effects of secondary hydrothermal fluids on gallium distribution and coordination in hot springs silica using Ga K-edge XANES en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gallium (Ga), a critical element in the electronics industry, is enriched in hot spring silica deposits (sinter) at concentrations comparable to, and in some cases greater than, bauxite, coal, and sphalerite deposits from which it is currently extracted. Focusing on well characterized Holocene and Pleistocene New Zealand sinters, we utilize synchrotron-X-ray fluorescence (sXRF) and Ga K-edge X-ray absorption near edge structure (XANES) spectroscopy to examine the spatial distribution of Ga as well as its changing coordination number. Ga+3 is the only observed oxidation state in the analyzed sinters. Gallium is predominantly found in tetrahedral coordination in sinter deposited from alkali chloride fluids, with analyses best matching Ga-aluminosilicate standards. However, Ga coordination is octahedral in sinter samples that have undergone alteration by acidic fluids/gases, associated with a change in hydrology from alkali-chloride to acid-sulfate fluid conditions. High Ga concentrations are found associated with both these coordination environments, with a heterogeneous distribution. Octahedral Ga is observed both as particles and in larger regions affected by Fe-rich fluid overprinting. The combined use of sXRF and XANES demonstrates an ability to fingerprint diagenesis and alteration in these complex geothermal settings where tetrahedral and octahedral Ga co-exist. The transition from tetrahedral to octahedral Ga also appears to mimic the inferred natural process forming lateritic bauxite deposits, where remobilized tetrahedral Ga is reconcentrated and adsorbed to oxides. A similar process may occur for sinter Ga enrichment, whereby introduced Ga in acidic conditions is adsorbed to oxide phases as the Fe-rich secondary fluids infiltrate porous sinter material. en-copyright= kn-copyright= en-aut-name=RoweM.C. en-aut-sei=Rowe en-aut-mei=M.C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=CampbellK.A. en-aut-sei=Campbell en-aut-mei=K.A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=StallardD.A. en-aut-sei=Stallard en-aut-mei=D.A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LyonB. en-aut-sei=Lyon en-aut-mei=B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LangendamA. en-aut-sei=Langendam en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KalininaE. en-aut-sei=Kalinina en-aut-mei=E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamanakaM. en-aut-sei=Yamanaka en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaR. en-aut-sei=Tanaka en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ChristopherT. en-aut-sei=Christopher en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=RuffS.W. en-aut-sei=Ruff en-aut-mei=S.W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NersezovaE. en-aut-sei=Nersezova en-aut-mei=E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OtaT. en-aut-sei=Ota en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HamiltonA. en-aut-sei=Hamilton en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=School of Environment, University of Auckland kn-affil= affil-num=2 en-affil=School of Environment, University of Auckland kn-affil= affil-num=3 en-affil=School of Environment, University of Auckland kn-affil= affil-num=4 en-affil=School of Environment, University of Auckland kn-affil= affil-num=5 en-affil=Australian Synchrotron Facility (Ansto) kn-affil= affil-num=6 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=7 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=8 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=9 en-affil=School of Chemical Sciences, University of Auckland kn-affil= affil-num=10 en-affil=Arizona State University, School of Earth And Space Exploration kn-affil= affil-num=11 en-affil=School of Environment, University of Auckland kn-affil= affil-num=12 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=13 en-affil=School of Environment, University of Auckland kn-affil= en-keyword=Hot springs kn-keyword=Hot springs en-keyword=New Zealand kn-keyword=New Zealand en-keyword=Gallium kn-keyword=Gallium en-keyword=Sinter kn-keyword=Sinter en-keyword=Synchrotron radiation kn-keyword=Synchrotron radiation en-keyword=Coordination number kn-keyword=Coordination number END start-ver=1.4 cd-journal=joma no-vol=236 cd-vols= no-issue= article-no= start-page=112768 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=An algorithm to calculate physical density of biomedical objects having 3 ≤ Zeff ≤ 20: an application study using clinical photon-counting computed tomography equipment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recently, photon-counting computed tomography (PC-CT) devices have become clinically available for X-ray diagnosis, and developments of analysis algorithms to generate various quantitative images have focused attention. This study proposes an algorithm to calculate the effective physical density (ρeff) of biological objects having an effective atomic number (Zeff) of 3–20. In our procedure, ρeff was determined when fitting the interaction cross sections (σs) to the measured linear attenuation coefficients (μs), which were determined from virtual monochromatic images (VMIs). In this process, the Zeff was analyzed in advance, and this information was fed back to the ρeff analysis. A key feature of our procedure is that it does not require calibration processes based on specific substances, which allow us to analyze any substance without making assumptions.
To validate the availability of the proposed algorithm, we conducted an experiment using a clinical PC-CT scanner. A multi-energy CT phantom, a water phantom, an in-house low-density phantom, food samples, and a chest phantom were scanned. The results showed that our procedure can calculate ρeff of water with an uncertainty of 4.5%. The academic significance of the present research results lies in demonstrating that the factors contributing to contrast, previously obtained from CT values, can be physically interpreted using information from Zeff and ρeff. This analysis cannot be performed with conventional single-energy CT scanners and is possible with PC-CT and dual-energy CT scanners. Our novel procedure is expected to provide useful additional information in X-ray diagnosis. 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=AsaharaTakashi en-aut-sei=Asahara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=MitaniMana en-aut-sei=Mitani en-aut-mei=Mana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=HigakiFumiyo en-aut-sei=Higaki en-aut-mei=Fumiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University kn-affil= affil-num=5 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=6 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=9 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= en-keyword=Computed tomography kn-keyword=Computed tomography en-keyword=Photon counting kn-keyword=Photon counting en-keyword=Physical density image kn-keyword=Physical density image en-keyword=Virtual monochromatic image kn-keyword=Virtual monochromatic image en-keyword=Diagnostic X-rays kn-keyword=Diagnostic X-rays END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=6 article-no= start-page=312 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Batch-Based VNF Deployment Mechanism for Privacy-Preserving Multi-Domain SFC Deployment Using Deep Reinforcement Learning en-subtitle= kn-subtitle= en-abstract= kn-abstract=Future 6G networks require higher performance and wider service coverage. Multi-domain Service Function Chain (SFC) deployment enables service provisioning across multiple network domains to meet these demands. However, when collaboration occurs among different network operators, privacy-preserving mechanisms are required to protect sensitive information such as internal topology and resource availability. Existing SIRM-based mechanisms, such as the Privacy-Preserving Deployment Mechanism (PPDM), address this challenge but suffer from structural limitations: PPDM performs whole-chain feasibility evaluation with extensive virtual occupation. This paper proposes a ℬ-Batch Sequential Deployment mechanism for privacy-preserving multi-domain SFC deployment. Instead of evaluating whole-chain feasibility at once, the proposed ℬ-Batch mechanism partitions each incoming SFC into fixed-size VNF batches and constructs a batch-level SIRM. This design confines virtual occupation to the current batch and reduces both its magnitude and duration while remaining fully compatible with the SIRM privacy model and the hierarchical multi-domain control architecture. A Deep Q-Network (DQN) is employed to learn substrate node selection policies based solely on SIRM-based state information, without exposing domain-internal topology or resource details. Simulation results on a three-domain AARNET substrate topology demonstrate that the proposed mechanism consistently improves deployment robustness under varying traffic intensities and SFC lengths, including short (3–6 VNFs), medium (6–9 VNFs), and long (9–12 VNFs) service chains. Compared with PPDM, the proposed ℬ-Batch mechanism achieves higher acceptance ratios under moderate-to-heavy traffic while reducing end-to-end delay and improving average substrate resource utilization. Node selection analysis further shows that smaller batch sizes preserve feasibility through compact node reuse, whereas larger batch sizes encourage broader substrate exploration. Overall, the proposed ℬ-Batch mechanism enhances feasibility preservation and deployment robustness in privacy-preserving multi-domain SFC orchestration. en-copyright= kn-copyright= en-aut-name=IrawanArif Indra en-aut-sei=Irawan en-aut-mei=Arif Indra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukushimaYukinobu en-aut-sei=Fukushima en-aut-mei=Yukinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Service Function Chain (SFC) kn-keyword=Service Function Chain (SFC) en-keyword=Virtual Network Embedding (VNE) kn-keyword=Virtual Network Embedding (VNE) en-keyword=privacy preservation kn-keyword=privacy preservation en-keyword=SIRM kn-keyword=SIRM en-keyword=Virtual Network Function (VNF) kn-keyword=Virtual Network Function (VNF) en-keyword=Deep Q-network (DQN) kn-keyword=Deep Q-network (DQN) END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=3 article-no= start-page=225 end-page=228 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=Determination of the Side Responsible for Bilateral Pneumothorax due to Pleural Communication en-subtitle= kn-subtitle= en-abstract= kn-abstract=Simultaneous bilateral spontaneous pneumothorax associated with pleuro-pleural communication is a rare but potentially life-threatening condition, most commonly occurring after major thoracic surgery. We report the case of an 81-year-old man with severe emphysema and a history of esophagectomy who presented with sudden-onset dyspnea. Chest computed tomography revealed bilateral pneumothorax with pleuro-pleural communication. Although bilateral chest tube drainage was performed, the primary side of air leakage could not be identified preoperatively. After induction of general anesthesia, a double-lumen endotracheal tube clamping test identified the right pleural cavity as the source of air leakage, thereby enabling appropriate thoracoscopic surgery. en-copyright= kn-copyright= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=NakajimaKumi en-aut-sei=Nakajima en-aut-mei=Kumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=TorigoeHidejiro en-aut-sei=Torigoe en-aut-mei=Hidejiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=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 and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=simultaneous bilateral spontaneous pneumothorax kn-keyword=simultaneous bilateral spontaneous pneumothorax en-keyword=pleuro-pleural communication kn-keyword=pleuro-pleural communication END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=3 article-no= start-page=219 end-page=223 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=Common Bile Duct Stone Formed Around an Ingested Fish Bone en-subtitle= kn-subtitle= en-abstract= kn-abstract=An 86-year-old man presented with epigastric pain. He had previously undergone distal gastrectomy with Roux-en-Y reconstruction. Computed tomography (CT) revealed a 32×17 mm common bile duct (CBD) stone with an internal 20 mm linear hyperdense component. Endoscopic removal was unsuccessful due to the size and impaction of the stone. Open choledochotomy retrieved multiple stones and a calcified fish bone, which was confirmed by infrared spectroscopy using the potassium bromide (KBr) wafer method. Although fish bone ingestion is relatively common, this case highlights that such foreign bodies can occasionally serve as a nidus for CBD stone formation, leading to unexpected and clinically significant pathologies. When CT demonstrates a linear high-attenuation intraductal structure, clinicians should suspect a bone fragment and follow a stepwise approach, considering early surgical intervention when endoscopic extraction is unsuccessful or likely to be challenging. en-copyright= kn-copyright= en-aut-name=HigashiKaitaro en-aut-sei=Higashi en-aut-mei=Kaitaro 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=OkabayashiTakehiro en-aut-sei=Okabayashi en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=4 en-affil=Department of 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 Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= en-keyword=common bile duct stone kn-keyword=common bile duct stone en-keyword=fish bone kn-keyword=fish bone en-keyword=Roux-en-Y kn-keyword=Roux-en-Y en-keyword=choledochotomy kn-keyword=choledochotomy END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=3 article-no= start-page=213 end-page=217 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=A Novel Flap Design to Reduce Urethral Complications in Anterolateral Thigh Phalloplasty: The Pipe Flap Technique en-subtitle= kn-subtitle= en-abstract= kn-abstract=Phalloplasty is one of the most challenging procedures in gender-affirming surgery, and urethral complications remain common despite numerous preventive efforts. No definitive solution has been established, and many patients still require subsequent corrective procedures. We designed a novel anterolateral thigh flap that creates a planned external fistula at the penile base to mitigate urethral complications. The fistula was closed in a second-stage procedure one year later, and the postoperative course was uneventful. We report a case of a transgender man treated with this two-stage “pipe flap” technique, resulting in satisfactory urinary function. This approach may offer a safe and less invasive option for mitigating urethral complications in phalloplasty. en-copyright= kn-copyright= en-aut-name=ImaiToshiro en-aut-sei=Imai en-aut-mei=Toshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeToshiyuki en-aut-sei=Watanabe en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeShiho en-aut-sei=Watanabe en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HayashiMasanobu en-aut-sei=Hayashi en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NambaYuzaburo en-aut-sei=Namba en-aut-mei=Yuzaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Plastic and Reconstructive Surgery, National Hospital Organization Tokyo Medical Center kn-affil= affil-num=4 en-affil=Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Gender Center, Okayama University Hospital kn-affil= en-keyword=phalloplasty kn-keyword=phalloplasty en-keyword=surgical flaps kn-keyword=surgical flaps en-keyword=transgender persons kn-keyword=transgender persons END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=3 article-no= start-page=203 end-page=212 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=Evaluation of Bone Mineral Density and Bone Structure in the Cervical and Thoracic Spine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dropped head syndrome, which has been increasingly reported in recent years, requires correction of cervical kyphosis and may require long-range fixation extending from the cervical to the thoracic spine. Assessing vertebral bone structure may be important for preventing instrumentation failure in the upper thoracic spine, which is a potential complication of surgery. In this study, we evaluated volumetric bone mineral density, trabecular bone porosity, and cortical calcification in the cervical and upper thoracic spine using three-dimensional (3D) trabecular structure measurement software. The study included 79 patients with cervical spine disorders who underwent various surgical procedures and preoperative imaging, including dual-energy X-ray absorptiometry and computed tomography (CT) scans from C3 to Th3. Quantitative analysis using specialized software assessed volumetric bone mineral density and trabecular and cortical bone parameters, and statistical analyses were performed to examine correlations between imaging metrics and indicators of bone fragility. Two-dimensional CT evaluation revealed different trends between cancellous and cortical bone in the cervical and thoracic spine, suggesting that detailed 3D evaluation may also be important. en-copyright= kn-copyright= en-aut-name=AoyamaShingo en-aut-sei=Aoyama en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaTerumasa en-aut-sei=Ikeda en-aut-mei=Terumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NangoNobuhito en-aut-sei=Nango en-aut-mei=Nobuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotoKoji en-aut-sei=Goto 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 Orthopedic Surgery, Kindai University Hospital kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Kindai University Hospital kn-affil= affil-num=3 en-affil=Ratoc System Engineering Co., Ltd. kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Kindai University Hospital kn-affil= en-keyword=cervical spine kn-keyword=cervical spine en-keyword=volumetric bone mineral density kn-keyword=volumetric bone mineral density en-keyword=three-dimensional trabecular structure measurement kn-keyword=three-dimensional trabecular structure measurement END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=3 article-no= start-page=195 end-page=202 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=HIP COMPASS®: A Mechanical Intraoperative Navigation Guide Associated with Improved Revision-Free Implant Survivorship after Ceramic-on-Ceramic Total Hip Arthroplasty at Minimum 10-Year Follow-up en-subtitle= kn-subtitle= en-abstract= kn-abstract=HIP COMPASS® has demonstrated improved accuracy in intraoperative support for the acetabular component insertion angle. We assessed long-term revision-free implant survivorship following total hip arthroplasty (THA) using HIP COMPASS, with ≥10 years of follow-up. We retrospectively analyzed 210 hips of 186 patients who underwent cementless THA with ceramic-on-ceramic bearing couples, with or without HIP COMPASS. The mean follow-up duration was 10.8 years in the HIp COMPASS group and 12.7 years in the control group. Overall, 86.0% and 78.2% of cups were placed within Lewinnek’s safe zone with and without HIP COMPASS, respectively. Variability in radiographic inclination and anteversion was greater in the control group than in the HIP COMPASS group. Dislocation rates were 3.2% in the control group and 1.2% in the HIP COMPASS group, with no significant difference between groups. The control group had a significantly higher revision rate than the HIP COMPASS group (7.3% vs. 1.2%). Use of HIP COMPASS was associated with improved long-term revision-free implant survivorship over ≥ 10 years and more consistent acetabular component positioning at an appropriate insertion angle, which may contribute to stable initial fixation. en-copyright= kn-copyright= en-aut-name=TeiYoshiaki en-aut-sei=Tei en-aut-mei=Yoshiaki 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=KimuraKeishi en-aut-sei=Kimura en-aut-mei=Keishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=SudaKen en-aut-sei=Suda en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= affil-num=1 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=2 en-affil=Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=3 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=4 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=5 en-affil=Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=6 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=7 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= en-keyword=HIP COMPASS® kn-keyword=HIP COMPASS® en-keyword=survivorship kn-keyword=survivorship en-keyword=total hip arthroplasty kn-keyword=total hip arthroplasty en-keyword=ceramic-on-ceramic kn-keyword=ceramic-on-ceramic END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=3 article-no= start-page=185 end-page=193 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=Reducing Hesitation in Resuscitation: Educational Effects of a Female-Appearing Simulator in Basic Life Support Training en-subtitle= kn-subtitle= en-abstract= kn-abstract=Women are less likely than men to receive timely defibrillation during out-of-hospital cardiac arrest. We investigated whether using a simulator that is visually modified to resemble a female affects learners’ attitudes, knowledge, and performance in basic life support (BLS) training. In a BLS simulation training, first-year medical students (n=220) used a standard gender-neutral simulator (control group) or a modified simulator with a female-like appearance (intervention group). Pre- and post-training questionnaires concerning attitudes and knowledge plus a post-training skills evaluation assessed the students’ training outcomes. The intervention group initiated chest compressions significantly faster than the control group (33.1 vs. 39.8 sec, p<0.01) and achieved a significantly higher rate of correct AED pad placement (64.2% vs. 38.5%, p<0.01). While performing the resuscitation on the female-appearing manikin, the intervention group showed significantly greater increases in self-efficacy (p<0.01) and larger decreases in discomfort about removing the patient’s clothes (p<0.01). They were also significantly more likely to recognize that chest compressions can be performed (p=0.016) and AED pads can be applied (p=0.015) without removing the patient’s underwear. Using a female-appearing simulator in BLS training was thus associated with faster chest compression initiation, more accurate AED pad placement, and improved gender-sensitive attitudes and knowledge. en-copyright= kn-copyright= en-aut-name=KuboTakuya en-aut-sei=Kubo en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KosakiYoshinori en-aut-sei=Kosaki en-aut-mei=Yoshinori 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=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=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, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Emergency, Critical Care and Disaster Medicine, 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=resuscitation kn-keyword=resuscitation en-keyword=basic life support kn-keyword=basic life support en-keyword=female simulator kn-keyword=female simulator en-keyword=medical education kn-keyword=medical education en-keyword=gender bias kn-keyword=gender bias END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=3 article-no= start-page=179 end-page=184 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=Oral Eicosapentaenoic Acid and Paclitaxel-Associated Peripheral Neuropathy: A Retrospective Study at Okayama University Hospital en-subtitle= kn-subtitle= en-abstract= kn-abstract=This retrospective study investigated whether eicosapentaenoic acid (EPA) reduces paclitaxel-associated chemotherapy-induced peripheral neuropathy (CIPN) and acute neuropathic pain in dyslipidemic cancer patients. The medical records of cancer patients treated with paclitaxel or nab-paclitaxel at Okayama University Hospital between January 2018 and December 2022 were reviewed. Patients receiving concomitant therapy for dyslipidemia were categorized as EPA users or non-EPA users. Numbness and pain severity were extracted from medical records. The primary endpoint was the change from baseline in Common Terminology Criteria for Adverse Events (CTCAE) grade for peripheral neuropathy and pain; groups were analyzed using the Mann–Whitney U test. Of 184 eligible patients, 18 received EPA. Bleeding events were more frequent in the EPA group; however, changes in numbness and pain did not differ significantly between groups at any time point. Overall, EPA did not show a preventive effect on paclitaxel-associated CIPN or acute neuropathic pain. Future studies should evaluate EPA in combination with other neuroprotective agents to better define its potential role in CIPN prevention. 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=KatayamaHideki en-aut-sei=Katayama en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= affil-num=1 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=eicosapentaenoic acid kn-keyword=eicosapentaenoic acid en-keyword=cancer patients kn-keyword=cancer patients en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=peripheral neuropathy kn-keyword=peripheral neuropathy en-keyword=cancer pain kn-keyword=cancer pain END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=3 article-no= start-page=169 end-page=178 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=Peripheral Blood T-Cell Receptor Repertoire and Host Immune Background in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=The association between peripheral blood T-cell receptor (TCR) repertoire and chemotherapy response remains unclear. We evaluated peripheral blood TCR repertoire and gut microbiota in 21 breast cancer patients receiving neoadjuvant chemotherapy (NAC) who were enrolled in the SBP-14 prospective cohort study between October 2019 and March 2022. We analyzed stool samples obtained pre-NAC and peripheral blood samples obtained pre- and post-NAC. The primary endpoint was the association between baseline peripheral blood TCR repertoire and treatment response. Eleven patients (52%) had hormone receptor-positive breast cancer. All patients received anthracyclines and taxanes, with anti-HER2 therapy for HER2-positive disease. TCR diversity (TCR alpha chain [TRA], p=0.095; TCR beta chain [TRB], p=0.051) and clonality (TRA, p=0.271; TRB, p=0.500) were not significantly associated with treatment response. Gut microbiota diversity was not correlated with TCR diversity (TRA: ρ=0.046, p=0.845; TRB: ρ=0.021, p=0.929); however, three bacterial orders (Erysipelotrichales, Bacillales, and Pasteurellales) were significantly associated with TCR repertoire. Baseline TCR repertoire was not associated with treatment response in this cohort of breast cancer patients. en-copyright= kn-copyright= en-aut-name=NakamuraYuki en-aut-sei=Nakamura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwamotoTakayuki en-aut-sei=Iwamoto en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KajiwaraYukiko en-aut-sei=Kajiwara en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HidaAkira en-aut-sei=Hida en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=MiyoshiYuichiro en-aut-sei=Miyoshi en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=IkedaMasahiko en-aut-sei=Ikeda en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=OgataRyohei en-aut-sei=Ogata en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KoikeYoshikazu en-aut-sei=Koike en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NomuraTsunehisa en-aut-sei=Nomura en-aut-mei=Tsunehisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TanakaKatsuhiro en-aut-sei=Tanaka en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakashimaKazutaka en-aut-sei=Nakashima en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamatsujiTomoki en-aut-sei=Yamatsuji en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TairaNaruto en-aut-sei=Taira en-aut-mei=Naruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=2 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=3 en-affil=Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=4 en-affil=Department of Pathology, Matsuyama Shimin 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 Endocrine Surgery, Kagawa Prefectural Center Hospital kn-affil= affil-num=7 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Breast and Thyroid Surgery, Fukuyama City Hospital kn-affil= affil-num=9 en-affil=Department of General Surgery, Kawasaki Medical School General Medical Center kn-affil= affil-num=10 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=11 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=12 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=13 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=14 en-affil=Department of General Surgery, Kawasaki Medical School General Medical Center kn-affil= affil-num=15 en-affil=Department of General Surgery, Kawasaki Medical School General Medical Center kn-affil= affil-num=16 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital kn-affil= en-keyword=TCR repertoire kn-keyword=TCR repertoire en-keyword=gut microbiota kn-keyword=gut microbiota en-keyword=neoadjuvant chemotherapy kn-keyword=neoadjuvant chemotherapy en-keyword=breast cancer kn-keyword=breast cancer END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=3 article-no= start-page=159 end-page=168 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=Self-Reported Adolescent Menstrual Symptoms and Delayed Gynecologic Consultation among Japanese Women with Endometriosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Endometriosis symptoms often first appear during adolescence, yet delays in seeking gynecologic consultation remain a persistent challenge worldwide. Despite growing international evidence, the specific patterns of symptom recognition and consultation delay among Japanese women — particularly in relation to self-monitoring behaviors and cultural barriers — remain poorly understood. This study aimed to provide foundational data to guide menstrual education and preconception care strategies by conducting a cross-sectional online survey with retrospective recall among women with endometriosis to assess menstrual characteristics and symptom patterns from adolescence to initial care seeking. The survey was conducted in Japan in January 2024 and enrolled 166 women with endometriosis and 200 controls. Participants reported current and adolescent menstrual characteristics, symptom recognition, analgesic and low-dose estrogen–progestin use, school/work impact, and age at first gynecologic consultation for menstrual problems. Women with endometriosis reported heavier bleeding, stronger pain, and greater school/work absence than controls, both currently and retrospectively. The median age at first recognition of heavy bleeding or school/work absence was 16 years, whereas consultation occurred at approximately 21-23 years, indicating a consultation delay of 5-6 years. Notably, while self-monitoring of symptoms was more frequent among women with endometriosis, it only modestly shortened consultation delays. This study provides evidence from Japan that consultation delay persists despite active self-monitoring of symptoms, highlighting the influence of educational and cultural barriers on health-seeking behavior. These findings underscore the importance of integrating menstrual education with clinical guidance to promote timely gynecologic consultation. en-copyright= kn-copyright= en-aut-name=IkedaTomoko en-aut-sei=Ikeda en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakatsukaMikiya en-aut-sei=Nakatsuka en-aut-mei=Mikiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Health Sciences, Okayama University kn-affil= en-keyword=endometriosis kn-keyword=endometriosis en-keyword=adolescence kn-keyword=adolescence en-keyword=menstrual disorders kn-keyword=menstrual disorders en-keyword=consultation delay kn-keyword=consultation delay en-keyword=health-seeking behavior kn-keyword=health-seeking behavior END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=18 article-no= start-page=1675 end-page=1687 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trisomy 8 alters chromatin conformations and activates Y chromosome genes in stem cells to drive a pre-leukemic state en-subtitle= kn-subtitle= en-abstract= kn-abstract=The mechanistic role of trisomy 8 in the development of myelodysplastic syndrome (MDS) remains poorly defined. Here, we generated a trisomy 8 mouse model by transferring a human chromosome 8 into murine embryonic stem cells and prospectively examined the effects on hematopoietic stem cells (HSC) by trisomy 8. The expression of inflammatory genes was enhanced, and hematopoietic programs mediated by transcription factors and polycomb repressive complex 2 (PRC2) were dysregulated in trisomy 8 HSC, which impaired their self-renewal and balanced differentiation. Trisomy 8 HSC altered the chromatin accessibility and conformations and activated Y chromosome genes, such as Uty/Kdm6c epigenetic modifier, which is known to demethylate histone H3K27me3 modification. The Uty gene facilitated the activation of PRC2-target and Runx1-target genes in leukemogenesis and drove the proliferation of human trisomy 8 leukemic cells. Since the RUNX1 gene is frequently mutated in patients with trisomy 8 MDS, its deletion attenuated the enhanced expression of inflammatory genes and mitigated the impaired self-renewal of trisomy 8 HSC in mice. Our findings reveal that trisomy 8 altered the transcriptional programs and chromatin conformations in HSC and drove a pre-malignant state through activating the expression of Uty, suggesting a route for the development of trisomy 8 MDS. en-copyright= kn-copyright= en-aut-name=BaiJie en-aut-sei=Bai en-aut-mei=Jie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ArakiKimi en-aut-sei=Araki en-aut-mei=Kimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurotakiDaisuke en-aut-sei=Kurotaki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Eerdunduleng en-aut-sei=Eerdunduleng en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SorinSupannika en-aut-sei=Sorin en-aut-mei=Supannika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HiramatsuKei en-aut-sei=Hiramatsu en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=HamashimaAi en-aut-sei=Hamashima en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IimoriMihoko en-aut-sei=Iimori en-aut-mei=Mihoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KikuchiKenta en-aut-sei=Kikuchi en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TerashimaMinoru en-aut-sei=Terashima en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KubotaSho en-aut-sei=Kubota en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KohrogiKensaku en-aut-sei=Kohrogi en-aut-mei=Kensaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HuangGang en-aut-sei=Huang en-aut-mei=Gang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OgawaMinetaro en-aut-sei=Ogawa en-aut-mei=Minetaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OshimuraMitsuo en-aut-sei=Oshimura en-aut-mei=Mitsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KazukiYasuhiro en-aut-sei=Kazuki en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SashidaGoro en-aut-sei=Sashida en-aut-mei=Goro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University kn-affil= affil-num=2 en-affil=Institute of Resource Development and Analysis, Kumamoto University kn-affil= affil-num=3 en-affil=Laboratory of Chromatin Organization in Immune Cell Development, International Research Center for Medical Sciences, Kumamoto University kn-affil= affil-num=4 en-affil=Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University kn-affil= affil-num=5 en-affil=Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University kn-affil= affil-num=6 en-affil=Department of Chromosome Biomedical Engineering, Integrated Medical Sciences, Graduate School of Medical Sciences, Tottori University kn-affil= affil-num=7 en-affil=Laboratory of Bioengineering, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences kn-affil= affil-num=8 en-affil=Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University kn-affil= affil-num=9 en-affil=Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University kn-affil= affil-num=10 en-affil=Laboratory of Chromatin Organization in Immune Cell Development, International Research Center for Medical Sciences, Kumamoto University kn-affil= affil-num=11 en-affil=Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University kn-affil= affil-num=12 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University kn-affil= affil-num=14 en-affil=Department of Cell Systems & Anatomy, Department of Pathology & Laboratory Medicine, UT Health San Antonio, Joe R. and Teresa Lozano Long School of Medicine, Mays Cancer Center at UT Health San Antonio kn-affil= affil-num=15 en-affil=Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University kn-affil= affil-num=16 en-affil=Chromosome Engineering Research Center, Tottori University kn-affil= affil-num=17 en-affil=Department of Chromosome Biomedical Engineering, Integrated Medical Sciences, Graduate School of Medical Sciences, Tottori University kn-affil= affil-num=18 en-affil=Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=3 article-no= start-page=e70104 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260429 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=VGLL3 Regulates DAPK2-Mediated Autophagy During Osteoblast Differentiation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vestigial-like family member 3 (VGLL3), a transcriptional cofactor of the TEA domain family, has been previously identified as a regulator of osteoblast differentiation. Building upon our previous findings, we investigated VGLL3 function in MC3T3-E1 osteoblasts using an integrated approach combining transcriptomic analysis and functional assays to identify its downstream effectors and explore associated autophagy mechanisms. RNA-seq analysis of Vgll3-knockdown (shVgll3) cells identified death-associated protein kinase 2 (DAPK2), a regulator of autophagy, as a downstream effector. Autophagic activity was examined using transmission electron microscopy and western blot analysis of LC3-II and p62 proteins. The effects of Dapk2 knockdown (shDapk2) on osteoblast differentiation were evaluated using qPCR, western blotting, alkaline phosphatase staining, and Alizarin Red staining. Rapamycin treatment was used to determine whether pharmacologic activation of autophagy could restore osteoblast function. Vgll3 knockdown significantly suppressed autophagic flux, as evidenced by fewer autophagic vacuoles, decreased LC3-II accumulation, and increased p62 expression. A comparable reduction in autophagic activity was observed in shDapk2 cells and was accompanied by impaired osteoblast differentiation. Rapamycin treatment partially restored autophagy and osteogenic differentiation in Vgll3-deficient cells. Finally, overexpression of DAPK2 partially rescued autophagic activity and osteogenic differentiation in shVgll3 cells, supporting its role as a key downstream functional effector. FOXM1 was further implicated as a potential transcriptional regulator contributing to DAPK2 expression. Collectively, our findings suggest that VGLL3 may influence osteogenic differentiation in osteoblasts, potentially involving DAPK2-associated autophagy. en-copyright= kn-copyright= en-aut-name=HeYuhan en-aut-sei=He en-aut-mei=Yuhan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WengYao en-aut-sei=Weng en-aut-mei=Yao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SitosariHeriati en-aut-sei=Sitosari en-aut-mei=Heriati kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhengYilin en-aut-sei=Zheng en-aut-mei=Yilin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=QuYaxin en-aut-sei=Qu en-aut-mei=Yaxin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkegameMika en-aut-sei=Ikegame en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamuraHirohiko en-aut-sei=Okamura en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Biology, Faculty of Dentistry, Universitas Gadjah Mada kn-affil= affil-num=5 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=autophagy kn-keyword=autophagy en-keyword=bone metabolism kn-keyword=bone metabolism en-keyword=death-associated protein kinase 2 kn-keyword=death-associated protein kinase 2 en-keyword=osteoblast differentiation kn-keyword=osteoblast differentiation en-keyword=vestigial-like 3 kn-keyword=vestigial-like 3 END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=3 article-no= start-page=419 end-page=427 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Predictors for Recurrences Within One Year Following Radical Nephrectomy for Non-metastatic Renal Cell Carcinomas en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: This study aimed to identify predictors of rapid recurrence following radical nephrectomy for non-metastatic renal cell carcinomas.
Patients and Methods: Patients with non-metastatic renal cell carcinoma who underwent radical nephrectomy between 2014 and 2024 at Okayama University Hospital were included. Rapid recurrence was defined as local or distant metastasis occurring within one year after radical nephrectomy, whereas recurrences occurring beyond one year were classified as non-rapid.
Results: Among a total of 194 patients, 37 (19%) experienced recurrence during a median follow-up of 37 months, with 16 (43%) being classified as experiencing rapid recurrence. The multivariate Cox hazard model revealed that microscopic venous invasion and a size of 60 mm or larger were predictors of rapid recurrence (hazard ratio=4.1, 95% confidence interval=1.5-11.4, p=0.006, and hazard ratio=8.0, 95% confidence interval=2.6-25.0, p<0.001, respectively). Dividing the entire cohort into four groups based on the presence of the two risk factors (0, 1: venous invasion, 1: tumor size, and 2), the median PFS was not estimable, 87, 67, and 7 months, respectively (p<0.001).
Conclusion: Microscopic venous invasion and tumor size of 60 mm or larger were identified as independent predictors of rapid recurrence following radical nephrectomy for non-metastatic renal cell carcinoma. en-copyright= kn-copyright= en-aut-name=BEKKUKENSUKE en-aut-sei=BEKKU en-aut-mei=KENSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KAWADATATSUSHI en-aut-sei=KAWADA en-aut-mei=TATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TOMINAGAYUSUKE en-aut-sei=TOMINAGA en-aut-mei=YUSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=KATAYAMASATOSHI en-aut-sei=KATAYAMA en-aut-mei=SATOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IWATATAKEHIRO en-aut-sei=IWATA en-aut-mei=TAKEHIRO 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=ARAKIMOTOO en-aut-sei=ARAKI en-aut-mei=MOTOO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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= en-keyword=Renal cell carcinoma kn-keyword=Renal cell carcinoma en-keyword=adjuvant therapy kn-keyword=adjuvant therapy en-keyword=radical nephrectomy kn-keyword=radical nephrectomy en-keyword=early recurrence kn-keyword=early recurrence en-keyword=metastases kn-keyword=metastases END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=1 end-page=17 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Afatinib Overcomes Osimertinib Resistance via Egfr V804F Mutation in a Syngeneic Egfr-Mutant Lung Cancer Mouse Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osimertinib is the standard first-line treatment for advanced EGFR-mutant non-small cell lung cancer. However, acquired resistance invariably develops, and identifying novel resistance pathways is clinically important as a substantial portion remains undefined. We used an immunocompetent syngeneic lung cancer mouse model harboring an Egfr exon 19 deletion (mDEL tumors) to establish acquired resistance. Osimertinib-resistant tumors were generated in vivo using a drug-holiday/re-challenge protocol. The resistance mechanism was identified using Sanger sequencing, receptor tyrosine kinase arrays, and western blotting. Egfr V804F knock-in cells were generated using CRISPR/Cas9, and their sensitivity to osimertinib and afatinib was assessed in vitro and in vivo. We established two distinct osimertinib-resistant tumor lines in a syngeneic lung cancer mouse model (mDEL OsiR #1/#3). The analysis revealed an on-target secondary Egfr V804F mutation (corresponding to human EGFR V802F) in both tumor lines. Importantly, Egfr V804F knock-in cells demonstrated significant osimertinib resistance, with a 5.7–10.5-fold increase in in vitro IC50 (mean, 8.2-fold), but remained highly sensitive to afatinib. Furthermore, afatinib effectively overcame osimertinib resistance in the V804F knock-in cell-derived mouse model. Consistently, afatinib treatment resulted in marked tumor shrinkage and suppression of EGFR signaling in the established mDEL OsiR #1/#3 in vivo. These findings establish secondary Egfr V804F/EGFR V802F as an on-target osimertinib resistance mechanism, providing a preclinical rationale for evaluating afatinib in biomarker-selected patients harboring this alteration. en-copyright= kn-copyright= en-aut-name=TanakaTakaaki en-aut-sei=Tanaka en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujitaniMasato en-aut-sei=Fujitani en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaokaMasataka en-aut-sei=Taoka en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShimomuraIwao en-aut-sei=Shimomura en-aut-mei=Iwao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=MoriShunta en-aut-sei=Mori en-aut-mei=Shunta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= en-aut-name=NishimuraTomoka en-aut-sei=Nishimura en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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=12 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=13 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=14 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=15 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=16 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=17 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=18 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=19 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=20 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=21 ORCID= en-aut-name=KatayamaRyohei en-aut-sei=Katayama en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 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=23 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= affil-num=12 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= affil-num=14 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= affil-num=15 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= affil-num=16 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= affil-num=17 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=19 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= affil-num=20 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= affil-num=22 en-affil=Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research kn-affil= affil-num=23 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= en-keyword=afatinib kn-keyword=afatinib en-keyword=EGFR-mutant NSCLC kn-keyword=EGFR-mutant NSCLC en-keyword=exon 19 deletion kn-keyword=exon 19 deletion en-keyword=osimertinib resistance kn-keyword=osimertinib resistance en-keyword=V802F (human EGFR)/V804F (murine Egfr) kn-keyword=V802F (human EGFR)/V804F (murine Egfr) END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=3 article-no= start-page=102635 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=Epidemiological and molecular characteristics of human-biting ticks in areas endemic to Japanese spotted fever: a prospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tick-borne diseases (TBDs) have become a great health concern worldwide. This study aimed to clarify the pathogenic and potentially pathogenic microorganisms carried by ticks that bite humans and to assess the risk of acquiring tick-borne infections in regions endemic for Japanese spotted fever. Tick specimens were prospectively collected from patients who presented with tick bites at 10 medical institutions in the Hiroshima, Okayama, and Kagawa prefectures, Japan between May 2023 and December 2024. The evaluated parameters included the estimated bite location, date of bite, patient age, tick species identification, and presence of TBD-associated pathogens in the collected ticks. Overall, 191 ticks were collected from 181 patients. Among patients with known sex, females were slightly more prevalent than males, and 45.9% of the patients were aged ≥ 70 years. Seasonal distribution demonstrated a peak incidence from April to July, with the highest number of cases observed in June (29.3%). Amblyomma testudinarium was the predominant species, accounting for 152 (79.6%) ticks, followed by Haemaphysalis hystricis (7.3%) and Haemaphysalis longicornis (6.8%). Nymphs represented the majority (83.8%), whereas adults and larvae accounted for 14.6% and 1.0%, respectively. A total of 27 ticks (14.1%) carried Rickettsia species, including two identified species (Rickettsia tamurae and Rickettsia monacensis) and one unclassified Rickettsia species. However, molecular analysis did not detect any known human pathogenic organisms, including Ehrlichia and Anaplasma species, Francisella tularensis, or Rickettsia japonica. Further epidemiological data regarding the abundance of tick-borne pathogens will provide valuable surveillance information with significant clinical utility for disease diagnosis and management. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SunamiHiroshi en-aut-sei=Sunami en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanoYasuhiro en-aut-sei=Nakano en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamotoKenta en-aut-sei=Nakamoto en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkazawaHidemasa en-aut-sei=Akazawa en-aut-mei=Hidemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HidaniYoshimi en-aut-sei=Hidani en-aut-mei=Yoshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KidaKouji en-aut-sei=Kida en-aut-mei=Kouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsurumiGo en-aut-sei=Tsurumi en-aut-mei=Go 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 General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Sumiyoshi Fujii 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 General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Numakuma Hospital kn-affil= affil-num=7 en-affil=Okayama Prefectural Institute for Environmental Science and Public Health kn-affil= affil-num=8 en-affil=Okayama Prefectural Institute for Environmental Science and Public Health kn-affil= affil-num=9 en-affil= kn-affil= en-keyword=Epidemiology kn-keyword=Epidemiology en-keyword=Japanese spotted fever kn-keyword=Japanese spotted fever en-keyword=Rickettsia species kn-keyword=Rickettsia species en-keyword=Tick bite kn-keyword=Tick bite en-keyword=Tick-borne disease kn-keyword=Tick-borne disease END start-ver=1.4 cd-journal=joma no-vol=40 cd-vols= no-issue=3 article-no= start-page=1570 end-page=1576 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260428 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Donor Cirrhosis Outcome Risk Estimator (CORE) Score on Recipient Outcomes Following Living-donor Liver Transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Several studies have investigated predictive factors for outcomes of living-donor liver transplantation (LDLT). However, few have examined the clinical significance of the Cirrhosis Outcome Risk Estimator (CORE) score on prognosis following LDLT. This study aimed to investigate the impact of donor CORE scores in predicting the outcomes of patients undergoing LDLT.
Patients and Methods: This single-center retrospective study included 362 adult LDLT recipients at our Institution between January 1998 and December 2024. Patient and graft survival rates were compared between the groups with low (≤0.05) and high (>0.05) CORE scores. Subsequently, multivariate analyses were performed to investigate prognostic factors for survival, including the CORE score.
Results: Patients in the group with a low CORE score had significantly better survival (p=0.001; 5-year, 85.3% vs. 76.2%) and graft survival (p=0.001; 5-year, 84.1% vs. 74.6%) than those with a high CORE score. Multivariate analyses identified the CORE score (>0.05) as an independent predictor of patient survival (hazard ratio=1.70, 95% confidence interval=1.01-2.62, p=0.018) and graft survival (hazard ratio=1.66, 95% confidence interval=1.07-2.57, p=0.024).
Conclusion: This study demonstrated the clinical significance of donor CORE scores in recipient outcomes after LDLT. Assessment of the donor CORE score may be useful for evaluating the quality of liver grafts and estimating recipient outcomes. en-copyright= kn-copyright= en-aut-name=TAKAGIKOSEI en-aut-sei=TAKAGI en-aut-mei=KOSEI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FUJITOMOKAZU en-aut-sei=FUJI en-aut-mei=TOMOKAZU kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YASUIKAZUYA en-aut-sei=YASUI en-aut-mei=KAZUYA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NISHIYAMATAKEYOSHI en-aut-sei=NISHIYAMA en-aut-mei=TAKEYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NAGAIYASUO en-aut-sei=NAGAI en-aut-mei=YASUO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OKADANAOHIRO en-aut-sei=OKADA en-aut-mei=NAOHIRO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YOKOYAMASHOHEI en-aut-sei=YOKOYAMA en-aut-mei=SHOHEI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FUJIWARATOSHIYOSHI en-aut-sei=FUJIWARA en-aut-mei=TOSHIYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Living-donor liver transplantation kn-keyword=Living-donor liver transplantation en-keyword=donor kn-keyword=donor en-keyword=recipient kn-keyword=recipient en-keyword=survival outcomes kn-keyword=survival outcomes en-keyword=Cirrhosis Outcome Risk Estimator score kn-keyword=Cirrhosis Outcome Risk Estimator score en-keyword=CORE kn-keyword=CORE END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=22 article-no= start-page=3694 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognosis Prediction Model After Upfront Surgery for Resectable Pancreatic Ductal Adenocarcinoma: A Multicenter Study (OS-HBP-2) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Upfront surgery (UFS) remains the standard treatment for patients with resectable pancreatic ductal adenocarcinoma (PDAC). We aimed to investigate the prognostic factors for survival after UFS in patients with resectable PDAC and to develop a prognostic prediction model. Methods: This multicenter, retrospective study included 603 patients who underwent UFS for resectable PDAC between January 2013 and December 2017. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival (OS). We constructed a prognostic prediction model for OS after UFS. An internal validation was performed to evaluate the discriminative performance of the model. Results: The 1-, 3-, and 5-year OS rates were 83.7%, 48.2%, and 37.5%, respectively. The Cox proportional hazards model showed that tumor size > 2 cm (hazard ratio [HR] 1.50, p = 0.001); tumor contact with the portal and superior mesenteric veins of ≤180° (HR 1.47, p = 0.003); carbohydrate antigen 19-9 levels of 40 to 500 U/mL (HR 1.59, p = 0.002) and ≥500 U/mL (HR 2.16, p < 0.001); and a modified Glasgow Prognostic Score of two (HR 1.56, p = 0.038) were predictors associated with OS. The prognostic prediction model for 5-year OS demonstrated an area under the curve of 0.68. The calibration plots indicate a concordance index of 0.63. Conclusions: We identified the preoperative prognostic factors for OS and developed a prognostic prediction model to estimate OS in patients undergoing UFS for resectable PDAC. Our model may be useful and internally validated for predicting OS. en-copyright= kn-copyright= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiokiMasayoshi en-aut-sei=Hioki en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=KojimaToru en-aut-sei=Kojima en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EndoYoshikatsu en-aut-sei=Endo en-aut-mei=Yoshikatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NobuokaDaisuke en-aut-sei=Nobuoka en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SuiKenta en-aut-sei=Sui en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=InagakiMasaru en-aut-sei=Inagaki en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShinouraSusumu en-aut-sei=Shinoura en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KimuraMasashi en-aut-sei=Kimura en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=AokiHideki en-aut-sei=Aoki en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Surgery, Fukuyama City Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Surgery, Okayama Saiseikai General Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Himeji Red Cross Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, Fukuyama City Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, Kagawa Prefectural Hospital kn-affil= affil-num=10 en-affil=Department of Surgery, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=11 en-affil=Department of Surgery, Tsuyama Chuo Hospital kn-affil= affil-num=12 en-affil=Department of Surgery, Matsuyama Shimin Hospital kn-affil= affil-num=13 en-affil=Department of Surgery, Tenwakai Matsuda 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 Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=pancreatic cancer kn-keyword=pancreatic cancer en-keyword=resectable kn-keyword=resectable en-keyword=upfront Surgery kn-keyword=upfront Surgery en-keyword=outcomes kn-keyword=outcomes END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=1 end-page=13 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=Atezolizumab + Chemotherapy in Older Patients With Lung Cancer in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pivotal phase 3 trials leading to the approvals of atezolizumab─chemotherapy combinations for non-small cell and extensive-stage small cell lung cancer (NSCLC and ES-SCLC) had strict eligibility criteria. J-TAIL-2 was a prospective, observational study in Japan that evaluated atezolizumab regimens for advanced NSCLC/ES-SCLC, including patients ineligible for global trials. The primary endpoint was 12-month overall survival (OS); safety and efficacy in subgroups defined by age, ECOG PS and/or G8 score, and creatinine clearance were key secondary endpoints. As of February 3, 2023, 1217 patients were treated in clinical practice based on Japanese labeling/treatment guidelines. Patients received atezolizumab with either carboplatin and nab-paclitaxel (atezo + CnP), carboplatin/cisplatin and pemetrexed (atezo + PP), or bevacizumab and carboplatin and paclitaxel (atezo + bev + CP) in the NSCLC cohort (n = 814) or with carboplatin and etoposide (atezo + CE) in the ES-SCLC cohort (n = 403). Overall, 53.5% were ≥ 70 years old, and 11.8% had ECOG PS ≥ 2; median G8 scores were 13 (NSCLC cohort) and 12 (ES-SCLC). Patients < 70 and ≥ 70 years had similar median (m)OS and progression-free survival (mPFS) across treatment regimens. Patients with ECOG PS < 2 and G8 score ≥ median had the highest mOS/PFS vs. patients with ECOG PS ≥ 2 and G8 score 0.5 log2 fold change) and linked to clinical outcomes reported in J-TAIL-2. IL-6, MUC-16, and KRT-19 were associated with shorter progression-free survival across multiple regimens. Granzyme A and B, immune activation markers, were elevated in responders who received atezolizumab + CnP and atezolizumab + bev + CP. High levels of baseline immune stimulation proteins were associated with irAEs across regimens. Protein expression changes were varied and regimen-dependent in subgroup analyses including older patients and those with EGFR-mutant tumors. These data warrant further investigation across different cancer types and atezolizumab-containing regimens to determine their relevance to efficacy and irAE occurrence of atezolizumab combination therapy. en-copyright= kn-copyright= en-aut-name=GotoYasushi en-aut-sei=Goto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishioMakoto en-aut-sei=Nishio en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OsoegawaAtsushi en-aut-sei=Osoegawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuchiEiki en-aut-sei=Kikuchi en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KimuraHideharu en-aut-sei=Kimura en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimizuJunichi en-aut-sei=Shimizu en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= en-aut-name=YoshinoIchiro en-aut-sei=Yoshino en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MisumiToshihiro en-aut-sei=Misumi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WatanabeYasutaka en-aut-sei=Watanabe en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KatakamiNobuyuki en-aut-sei=Katakami en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KisoharaAkira en-aut-sei=Kisohara en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamaguchiMasafumi en-aut-sei=Yamaguchi en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KurokiHirotaka en-aut-sei=Kuroki en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= en-aut-name=AshimuraHisao en-aut-sei=Ashimura en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TanakaMisa en-aut-sei=Tanaka en-aut-mei=Misa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=GemmaAkihiko en-aut-sei=Gemma en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Kanazawa University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Tohoku University Hospital kn-affil= affil-num=9 en-affil=Department of Thoracic Oncology, Kansai Medical University kn-affil= affil-num=10 en-affil=Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital kn-affil= affil-num=11 en-affil=Department of Data Science, National Cancer Center Hospital East kn-affil= affil-num=12 en-affil=Department of Thoracic Oncology, Saitama Cancer Center kn-affil= affil-num=13 en-affil=Department of Pulmonary Medicine and Medical Oncology Takarazuka City Hospital Takarazuka Japan kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Kasukabe Medical Center kn-affil= affil-num=15 en-affil=Department of Thoracic Oncology, NHO Kyushu Cancer Center kn-affil= affil-num=16 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=17 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=18 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=19 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=20 en-affil=Nippon Medical School kn-affil= en-keyword=atezolizumab kn-keyword=atezolizumab en-keyword=biomarker kn-keyword=biomarker en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=plasma protein kn-keyword=plasma protein en-keyword=small cell lung cancer kn-keyword=small cell lung cancer END start-ver=1.4 cd-journal=joma no-vol=195 cd-vols= no-issue= article-no= start-page=110231 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=Biliverdin supplementation in perfusate and preservation solution attenuates ischemia-reperfusion injury in a rat donation-after-circulatory-death heart transplantation model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Heart transplantation faces a persistent donor shortage; therefore, hearts from donation after circulatory death have become a feasible option despite unavoidable warm ischemia and subsequent ischemia-reperfusion injury. Biliverdin, an endogenous bile pigment with strong antioxidant and anti-inflammatory properties, has shown protective effects against ischemia-reperfusion injury in several organ transplantation models. Whether biliverdin attenuates warm ischemic injury in donation after circulatory death heart transplantation remains unclear. This study evaluated biliverdin supplementation in the perfusate and preservation solution in a rat donation after circulatory death model.
Methods: Circulatory death was induced under deep anesthesia, and warm ischemia was maintained for 18 minutes, including the mandatory 5-minute stand-off period. Donor hearts were then flushed and subsequently cold-stored in the same biliverdin-supplemented extracellular-type trehalose–containing Kyoto solution, whereas control grafts received extracellular-type trehalose–containing Kyoto without biliverdin at both stages before heterotopic transplantation. Grafts were assessed at 3 and 24 hours after reperfusion (n = 6 per group). Evaluations included early graft recovery, myocardial injury markers, histological and ultrastructural changes, and inflammatory and stress-response gene expression.
Results: Biliverdin significantly improved early graft recovery, shortening reanimation time and increasing left ventricular fractional shortening at 24 hours. Serum troponin I levels were lower in biliverdin-treated grafts. Biliverdin also reduced histological injury and inflammatory cell infiltration. Ultrastructural analysis showed preserved mitochondrial architecture and ultrastructural integrity. Early proinflammatory gene expression was suppressed.
Conclusion: Biliverdin supplementation in the perfusate and preservation solution attenuates ischemia-reperfusion injury in the experimental rat donation after circulatory death heart transplantation model. These findings provide proof of concept for further mechanistic and translational evaluation of biliverdin for myocardial protection in donation after circulatory death. en-copyright= kn-copyright= en-aut-name=TokiokaKohei en-aut-sei=Tokioka en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirayamaTakahiro en-aut-sei=Hirayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=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=AgetaKohei en-aut-sei=Ageta en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IgawaTakuro en-aut-sei=Igawa en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AokageToshiyuki en-aut-sei=Aokage en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology kn-affil= affil-num=9 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=20260603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Classification of hypotony maculopathy based on optical coherence tomography findings and risk factors for visual outcomes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose To classify hypotony maculopathy (HM) using optical coherence tomography (OCT) findings and to investigate the associations among morphological types, clinical factors, and visual outcomes.
Methods We retrospectively reviewed 60 eyes that developed HM after trabeculectomy. HM was classified according to the distribution and configuration of chorioretinal undulations on OCT B-scans. Between-group comparisons were performed, and factors associated with the morphological classification and logMAR best-corrected visual acuity (BCVA) at 3 months after HM onset (3-month BCVA) were determined.
Results HM was classified into three OCT-based types by categorizing chorioretinal undulations as folds (U-shaped troughs) or spikes (V-shaped troughs): Type 1, folds only on vertical scans; Type 2, folds on both vertical and horizontal scans; Type 3, folds on both scans, with spikes. Axial length in Type 3 was significantly longer than that in Type 2 (P = 0.034). Subfoveal choroidal thickness was significantly thinner in Type 3 than in Types 1 and 2 (both P < 0.001). Minimum intraocular pressure (IOP) was significantly higher in Type 1 than in Types 2 and 3 (P < 0.001 and P = 0.003, respectively), with no difference between Types 2 and 3. In multivariable analysis using Type 1 as the reference group, minimum IOP was significantly associated with Type 2 (P = 0.001). For Type 3, both minimum IOP (P = 0.03) and subfoveal choroidal thickness (P = 0.02) showed significant associations. The 3-month BCVA was significantly worse in Type 3 than in Types 1 and 2 (P < 0.001 and P = 0.007, respectively). Chorioretinal spikes and preoperative BCVA were significantly associated with 3-month BCVA (both P < 0.001). Exploratory receiver operating characteristic analysis assessed the discriminative ability of subfoveal choroidal thickness for the presence of chorioretinal spikes (AUC = 0.876). A thickness of 195.0 μm was identified as a candidate cutoff value (sensitivity 92.3% and specificity 72.3%).
Conclusions In HM following TLE, chorioretinal spikes and preoperative BCVA are significantly associated with the 3-month BCVA. In HM, a thin subfoveal choroid (< 195.0 μm), may be associated with chorioretinal spikes, suggesting the need for careful postoperative IOP and OCT monitoring. en-copyright= kn-copyright= en-aut-name=KanzakiYuki en-aut-sei=Kanzaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMiyuki en-aut-sei=Fujiwara en-aut-mei=Miyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiwaraRie en-aut-sei=Fujiwara en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkamotoSara en-aut-sei=Okamoto en-aut-mei=Sara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MitsuiNaruka en-aut-sei=Mitsui en-aut-mei=Naruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HosokawaMio Morizane en-aut-sei=Hosokawa en-aut-mei=Mio Morizane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HayashiJunko en-aut-sei=Hayashi en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MasudaYuki en-aut-sei=Masuda en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AkatsukaRiku en-aut-sei=Akatsuka en-aut-mei=Riku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TsujiAkihiro en-aut-sei=Tsuji en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Hypotony maculopathy kn-keyword=Hypotony maculopathy en-keyword=Optical coherence tomography kn-keyword=Optical coherence tomography en-keyword=Trabeculectomy kn-keyword=Trabeculectomy en-keyword=Chorioretinal spike kn-keyword=Chorioretinal spike en-keyword=Choroidal thickness kn-keyword=Choroidal thickness en-keyword=Visual outcomes kn-keyword=Visual outcomes END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=3 article-no= start-page=104848 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=Predictors of therapeutic response and pain after near-infrared photoimmunotherapy in head and neck cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Near-infrared photoimmunotherapy (NIR-PIT) has been approved by the Japanese national health insurance for approximately five years, and clinical experience has steadily accumulated. However, reports analyzing treatment outcomes and pain-related factors remain limited. This study aimed to identify predictors of therapeutic response and pain following NIR-PIT.
Methods: This retrospective cohort study included 25 patients who underwent NIR-PIT for head and neck cancer between January 2021 and June 2025. Lesion diameter and thickness were evaluated in relation to complete response (CR), and the frequency and predictors of post-treatment pain were assessed.
Results: Among 22 evaluable patients, eight achieved CR. Lesions with a shorter longest diameter and thinner thickness were significantly associated with higher CR rates (p = 0.011 and p = 0.024). Moderate-to-severe pain (Numerical Rating Scale ≥4) occurred in 18 of 48 treatment cycles (37.5%) but was significantly less frequent in patients with a history of reconstructive surgery (p = 0.017).
Conclusions: NIR-PIT demonstrated particularly favorable efficacy for short, thin lesions, suggesting that early introduction of treatment may be associated with improved therapeutic outcomes. A history of reconstructive surgery was associated with reduced post-treatment pain, highlighting the importance of individualized treatment and pain management strategies in head and neck cancer patients undergoing NIR-PIT. en-copyright= kn-copyright= en-aut-name=MatsumotoJunya en-aut-sei=Matsumoto en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MakinoTakuma en-aut-sei=Makino en-aut-mei=Takuma 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=FujimotoShohei en-aut-sei=Fujimoto en-aut-mei=Shohei 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 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= en-keyword=Near-infrared photoimmunotherapy kn-keyword=Near-infrared photoimmunotherapy en-keyword=Head and neck cancer kn-keyword=Head and neck cancer en-keyword=Treatment response kn-keyword=Treatment response en-keyword=Tumor size kn-keyword=Tumor size en-keyword=Tumor thickness kn-keyword=Tumor thickness en-keyword=Pain kn-keyword=Pain END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=5671446 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=Arthroscopically Confirmed Complete Healing of Anterior Cruciate Ligament Avulsion Fracture Following Four‐Corner Pullout Repair Using Ultrahigh‐Molecular‐Weight Polyethylene Tapes: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a case of tibial insertion avulsion fracture of the anterior cruciate ligament (ACL). A 10-year-old boy who fell from a skateboard was diagnosed with a tibial insertion avulsion fracture of the ACL and was treated arthroscopically. The avulsed fragment was provisionally fixed with guide pins inserted into its four corners, and the lateral view was checked to avoid penetration of the growth plate. Two ultrahigh-molecular-weight polyethylene tapes were passed through the ACL just above its tibial insertion, pulled through the four-corner bone tunnels in an X-shaped configuration, and tightened. The patient was immobilized for 3 weeks, and partial weight bearing was initiated at 4 weeks. Bone union was confirmed at 6 months using plain radiographs, and second-look arthroscopy and implant removal were performed 8 months postoperatively. During arthroscopy, complete union with smooth continuity of the articular cartilage at the fracture site and a stable ACL were observed. The patient had a full knee range of motion and no pain at the final follow-up. en-copyright= kn-copyright= en-aut-name=KoharaToshiki en-aut-sei=Kohara en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=MiyazawaShinichi en-aut-sei=Miyazawa en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FurumatsuTakayuki en-aut-sei=Furumatsu en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YokoyamaYusuke en-aut-sei=Yokoyama en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TamuraMasanori en-aut-sei=Tamura en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawadaKoki en-aut-sei=Kawada en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HasegawaTsubasa en-aut-sei=Hasegawa en-aut-mei=Tsubasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery , NHO Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery , Japanese Red Cross Okayama Hospital kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences 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=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Switchable photoluminescence of europium(iii) complexes with chromonylhydrazones en-subtitle= kn-subtitle= en-abstract= kn-abstract=Europium(III) complexes bearing 4-hydroxy- or 4-methyl-N′-((6-methyl-4-oxo-4H-chromen-3-yl)methylene)benzohydrazide (HL1 or HL2) showed characteristic EuIII 5D0 → 7FJ (J = 0–4) luminescence both in acetonitrile and in solid states with relatively high Φtot values. The luminescence was quenched not only by adding triethylamine in acetonitrile, but also by heating the solid sample, and recovered by adding perchloric acid in solution or by diffusion of HCl vapor to the resulting solid sample. en-copyright= kn-copyright= en-aut-name=KameiAsahi en-aut-sei=Kamei en-aut-mei=Asahi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaitoDaisuke en-aut-sei=Saito en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakaharaKazuma en-aut-sei=Takahara en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NoseKeito en-aut-sei=Nose en-aut-mei=Keito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=YoshidaMasaki en-aut-sei=Yoshida en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatoMasako en-aut-sei=Kato en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SuzukiTakayoshi en-aut-sei=Suzuki en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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 Science, Hokkaido University kn-affil= affil-num=3 en-affil=Graduate School of Science, University of Hyogo kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Department of Chemistry, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Science, The University of Osaka kn-affil= affil-num=7 en-affil=School of Biological and Environmental Sciences, Kwansei Gakuin University kn-affil= affil-num=8 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=19 cd-vols= no-issue=3 article-no= start-page=491 end-page=498 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260317 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful management and 10-year survival of a rectal neuroendocrine tumor with rare systemic metastases via a non-portal venous pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metastatic neuroendocrine tumors (NETs) typically involve the liver and lymph nodes. Metastases in the orbit, heart, and ovary are rare and present unique clinical challenges. We report a woman who was 70 years old at the time of initial presentation with liver metastases from a rectal neuroendocrine tumor. Following a right hepatectomy for liver metastases, she remained free of hepatic recurrence for 10 years. Notably, four years after the right hepatectomy, she developed new metastases in the left orbit, right ventricle, and left ovary, with diplopia as the sole clinical symptom. This clinical course suggests a distinct metastatic pathway associated with the lower rectum that bypasses the portal circulation, consistent with the dual drainage system of the rectal region. Management involved a strategic multimodal approach that includes systemic therapy with everolimus and lanreotide as well as targeted surgical resectioning of the cardiac and ovarian lesions. The orbital lesion achieved a complete response through systemic therapy alone, preserving visual function. Currently, 10 years after the initial treatment, the patient maintains an excellent performance status (ECOG PS 0) while receiving peptide receptor radionuclide therapy (PRRT). This case demonstrates that recognizing atypical metastatic pathways and employing strategic multimodal therapies can achieve long-term survival and functional preservation in rectal NETs. en-copyright= kn-copyright= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=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=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TerasawaHiroyuki en-aut-sei=Terasawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KuiseTakashi en-aut-sei=Kuise en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama Red Cross Hospital kn-affil= affil-num=9 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=Rectal neuroendocrine tumor kn-keyword=Rectal neuroendocrine tumor en-keyword=Rare metastases kn-keyword=Rare metastases en-keyword=Multimodal treatment kn-keyword=Multimodal treatment END start-ver=1.4 cd-journal=joma no-vol=2026 cd-vols= no-issue=1 article-no= start-page=8863202 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=Selective ARID1A Loss Restricted to the Undifferentiated Component of a Mismatch Repair‐Deficient Gastric Carcinoma: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mismatch repair-deficient (dMMR) gastric carcinomas often harbor ARID1A alteration, but a sharply demarcated undifferentiated/rhabdoid component with selective ARID1A loss is uncommon and may create a diagnostic dilemma. An 80-year-old man underwent esophagogastroduodenoscopy for anemia, which revealed a circumferential Borrmann Type 3 lesion in the gastric body, and distal gastrectomy was performed. Histologically, the tumor was composed predominantly of undifferentiated carcinoma with focal rhabdoid features and a minute well-differentiated adenocarcinoma component, with an abrupt transition between the two. Immunohistochemistry showed loss of nuclear MLH1 and PMS2 in both components, whereas loss of ARID1A expression was confined to the undifferentiated component; SMARCB1 (INI1), SMARCA2 (BRM), and SMARCA4 (BRG1) were retained. EBER in situ hybridization was negative. Because gene-level testing, MSI testing, and MLH1 promoter methylation analysis were not performed, the molecular basis of the dMMR phenotype and ARID1A loss could not be determined. The restricted scope of molecular testing limits the ability to draw broad or generalizable conclusions and to fully establish clinicopathological correlations. The value of this report is, therefore, not mechanistic proof but recognition of a practical morphologic-immunophenotypic observation: When a gastric carcinoma shows a sharply demarcated shift from differentiated to undifferentiated/rhabdoid morphology, dMMR should be considered, and selective ARID1A loss in the undifferentiated component may be associated with dedifferentiation. These findings should be interpreted with caution as preliminary, hypothesis-generating observations that require validation in larger studies with more extensive molecular profiling. en-copyright= kn-copyright= en-aut-name=OmoteRika en-aut-sei=Omote en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamanoRyosuke en-aut-sei=Hamano en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaShinya en-aut-sei=Otsuka en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Diagnostic Pathology, NHO Fukuyama Medical Center kn-affil= affil-num=2 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=3 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pathology, Okayama University Hospital kn-affil= en-keyword=ARID1A kn-keyword=ARID1A en-keyword=carcinoma kn-keyword=carcinoma en-keyword=DNA mismatch repair deficiency kn-keyword=DNA mismatch repair deficiency en-keyword=rhabdoid features kn-keyword=rhabdoid features en-keyword=stomach neoplasms kn-keyword=stomach neoplasms en-keyword=SWI/SNF complex kn-keyword=SWI/SNF complex en-keyword=undifferentiated kn-keyword=undifferentiated END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=4 article-no= start-page=829 end-page=838 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Differences in drug efficacy and prognosis between primary and metastatic sites for de novo stage IV breast cancer: an exploratory analysis of a phase III trial, JCOG1017 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Breast cancer is a highly heterogeneous disease, with biological factors like estrogen receptor, progesterone receptor, and HER2 receptor differing between primary and metastatic sites, potentially affecting treatment response.
This exploratory analysis aims to differentiate drug efficacy and long-term prognosis between these sites in stage IV breast cancer.
Methods Patients from JCOG1017, a phase III trial evaluating the role of primary tumor resection, who received primary systemic therapy (PST) were evaluated at three months. In this analysis, treatment response was assessed separately in primary and metastatic sites. Patients were categorized into four groups: discordant I (primary non-PD, metastatic PD), concordant I (both PD), discordant II (primary PD, metastatic non-PD), and concordant II (both non-PD).
Results Among 271 patients, overall discordance proportion of treatment response between primary and metastatic sites was 25.1%. Group distribution was 24.7% (discordant I), 9.6% (concordant I), 0.4% (discordant II), and 65.3% (concordant II). Discordance was more frequent in luminal (28.9%), triple-negative (25.0%), and luminal-HER2 (22.0%) subtypes than in HER2-enriched (11.1%). Survival analysis showed prognostic differences: concordant II, with both sites non-PD, demonstrated the most favorable outcome compared with discordant I (HR 0.556; 95% confidence interval, 0.396–0.782).
Conclusions One-fourth of patients exhibited discordant responses between primary and metastatic sites in early treatment phases. These discrepancies were associated with survival differences, emphasizing the importance of evaluating both primary and metastatic lesions when assessing efficacy and determining treatment strategies in de novo stage IV breast cancer. en-copyright= kn-copyright= en-aut-name=TanakaKiyo en-aut-sei=Tanaka en-aut-mei=Kiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimomuraAkihiko en-aut-sei=Shimomura en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshitobiMakoto en-aut-sei=Ishitobi en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamanakaTakashi en-aut-sei=Yamanaka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsukiokiTakahiro en-aut-sei=Tsukioki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwataHiroji en-aut-sei=Iwata en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujisawaTomomi en-aut-sei=Fujisawa en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SasakiKeita en-aut-sei=Sasaki en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SadachiRyo en-aut-sei=Sadachi en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KajikawaRiku en-aut-sei=Kajikawa en-aut-mei=Riku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SakaiTakehiko en-aut-sei=Sakai en-aut-mei=Takehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SagaraYasuaki en-aut-sei=Sagara en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShigematsuHideo en-aut-sei=Shigematsu en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OzakiYukinori en-aut-sei=Ozaki en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NozawaKazuki en-aut-sei=Nozawa en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SudoKazuki en-aut-sei=Sudo en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 ORCID= en-aut-name=TerataKaori en-aut-sei=Terata en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IshibaToshiyuki en-aut-sei=Ishiba en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=FukudaHaruhiko en-aut-sei=Fukuda en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 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=22 ORCID= affil-num=1 en-affil=Department of Breast Surgery, Toranomon Hospital kn-affil= affil-num=2 en-affil=Department of Breast and Medical Oncology, National Center for Global Health and Medicine kn-affil= affil-num=3 en-affil=Department of Breast Surgery, Osaka Habikino Medical Center kn-affil= affil-num=4 en-affil=Department of Breast Surgery, Kanagawa Cancer Center 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 Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=7 en-affil=Department of Breast Oncology, Aichi Cancer Center kn-affil= affil-num=8 en-affil=Department of Breast Oncology, Gunma Prefectural Cancer Center kn-affil= affil-num=9 en-affil=Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=10 en-affil=Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=11 en-affil=Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=12 en-affil=Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=13 en-affil=Department of Breast Surgery, Sagara Hospital kn-affil= affil-num=14 en-affil=Department of Breast Surgery, Hiroshima University Hospital kn-affil= affil-num=15 en-affil=Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=16 en-affil=Department of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=17 en-affil=Department of Medical Oncology, National Cancer Center Hospital kn-affil= affil-num=18 en-affil=Department of General Internal Medicine, National Cancer Center Hospital East kn-affil= affil-num=19 en-affil=Department of Breast and Endocrine Surgery, Akita University Hospital kn-affil= affil-num=20 en-affil=Department of Breast Surgery, Institute of Science Tokyo Hospital kn-affil= affil-num=21 en-affil=Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=22 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=Discordance of treatment response between primary and metastatic sites kn-keyword=Discordance of treatment response between primary and metastatic sites en-keyword=De novo stage IV breast cancer kn-keyword=De novo stage IV breast cancer en-keyword=Primary systemic therapy kn-keyword=Primary systemic therapy en-keyword=Overall survival kn-keyword=Overall survival END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=3 article-no= start-page=528 end-page=536 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical complete response and predictive factors in HER2-positive early breast cancer treated with neoadjuvant chemotherapy aimed at omission of surgery: an exploratory analysis of the JCOG1806 trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose The JCOG1806 trial (jRCTs031190129) is underway to evaluate the omission of surgery in patients with human epidermal growth factor receptor (HER2)-positive early breast cancer who have a clinical complete response (cCR) after primary systemic therapy (PST). We aimed to assess the cCR rate in this trial and identify predictive factors.
Methods HER2-positivity was defined as an immunohistochemistry (IHC) score of 3 + or in situ hybridization-positivity. A cCR was defined as the absence of detectable lesions upon palpation, contrast-enhanced magnetic resonance imaging, and ultrasonography; biopsy-based confirmation was optional in hormone receptor (HR)-negative cases and mandatory in HR-positive cases. Multivariate logistic regression analyses were used to identify predictors of a cCR.
Results The cCR rate was 57.6% (196/340 patients; 95% confidence interval [CI]: 52.2–63.0%). Strongly estrogen-receptor (ER)-positive tumors (≥ 10%) were significantly less likely to have a cCR than ER-negative tumors (odds ratio [OR], 0.41; 95% CI: 0.20–0.81). IHC 3 + tumors had higher cCR rates than IHC 1 + or 2 + tumors (OR, 2.19; 95% CI: 1.01–4.74). Compared with histological grade I tumors, cCR odds were higher in grade II (OR: 2.92; 95% CI: 1.07–7.93) and III (OR: 4.90; 95% CI: 1.76–13.7) tumors. Among patients without a cCR patients undergoing surgery, 22.2% were diagnosed with ypT0 tumors upon analysis of surgical specimens.
Conclusion ER-negativity, an IHC score of 3 + , and a higher histological grade were independent predictors of a cCR. Identifying these features may improve the feasibility and safety of surgery omission for patients with HER2-positive early breast cancer. en-copyright= kn-copyright= en-aut-name=ShigematsuHideo en-aut-sei=Shigematsu en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujisawaTomomi en-aut-sei=Fujisawa en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwataHiroji en-aut-sei=Iwata en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshibaToshiyuki en-aut-sei=Ishiba en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OzakiYukinori en-aut-sei=Ozaki en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakaiTakehiko en-aut-sei=Sakai en-aut-mei=Takehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SagaraYasuaki en-aut-sei=Sagara en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimomuraAkihiko en-aut-sei=Shimomura en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SudoKazuki en-aut-sei=Sudo en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TerataKaori en-aut-sei=Terata en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=NozawaKazuki en-aut-sei=Nozawa en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SasakiKeita en-aut-sei=Sasaki en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MitomeNoriko en-aut-sei=Mitome en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SadachiRyo en-aut-sei=Sadachi en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ShibataTaro en-aut-sei=Shibata en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 ORCID= affil-num=1 en-affil=Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University Hospital kn-affil= affil-num=2 en-affil=Gunma Prefectural Cancer Center kn-affil= affil-num=3 en-affil=Aichi Cancer Center kn-affil= affil-num=4 en-affil=Graduate School of Medical Sciences, Nagoya City University kn-affil= affil-num=5 en-affil=Institute of Science Tokyo Hospital kn-affil= affil-num=6 en-affil=Cancer Institute Hospital of the Japanese Foundation for Cancer Research kn-affil= affil-num=7 en-affil=Cancer Institute Hospital of the Japanese Foundation for Cancer Research kn-affil= affil-num=8 en-affil=Hakuaikai Sagara Hospital kn-affil= affil-num=9 en-affil=National Center for Global Health and Medicine kn-affil= affil-num=10 en-affil=National Cancer Center Hospital kn-affil= affil-num=11 en-affil=Akita University Hospital kn-affil= affil-num=12 en-affil=National Cancer Center Hospital East kn-affil= affil-num=13 en-affil=Graduate School of Medical Sciences, Nagoya City University kn-affil= affil-num=14 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=15 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=16 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=17 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=18 en-affil=Okayama University Hospital kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Primary systemic therapy kn-keyword=Primary systemic therapy en-keyword=HER2 kn-keyword=HER2 en-keyword=cCR kn-keyword=cCR en-keyword=Omission of surgery kn-keyword=Omission of surgery END start-ver=1.4 cd-journal=joma no-vol=208 cd-vols= no-issue=6 article-no= start-page=2124 end-page=2133 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260415 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Decreased renal function predicts severe cytokine release syndrome after CAR-T-cell therapy for large B-cell lymphoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cytokine release syndrome (CRS) remains a major toxicity of chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL), and robust pre-infusion predictors are needed for risk-adapted management. We retrospectively analysed LBCL patients in the Japanese nationwide registry who underwent CD19 CAR-T-cell therapy between 2019 and 2024. Among 900 patients (median age 62 years), cumulative incidences of CRS within 30 days after infusion were 75.0% for any grade, 20.8% for grade ≥ 2 and 14.0% for grade ≥ 3. In multivariable analysis, lower estimated glomerular filtration rate (eGFR) (adjusted hazard ratio [aHR] 1.108 per 10 mL/min per 1.73 m2 decrease; 95% confidence interval [CI] 1.015–1.209; p = 0.022), higher ferritin (aHR 1.006 per 100 ng/mL; 95% CI 1.001–1.010; p = 0.016), C-reactive protein (CRP) (aHR 1.142 per mg/dL; 95% CI 1.091–1.195; p < 0.001) and lactate dehydrogenase (LDH) (aHR 1.073 per 100 U/L; 95% CI 1.008–1.142; p = 0.028) independently predicted grade ≥ 2 CRS. We then built a four-factor CRS pre-infusion risk evaluation model, cytokine release syndrome-pre-infusion risk evaluation (CRS-PRE), that stratified grade ≥ 2 CRS risk into low, intermediate and high groups with incidences of 2.8%, 26.0% and 50.0% respectively. Decreased eGFR, a surrogate of host renal reserve, with elevated ferritin, CRP and LDH emerged as predictors of high-grade CRS. The CRS-PRE may facilitate risk-adapted monitoring and intervention in clinical practice. en-copyright= kn-copyright= en-aut-name=AraiYasuyuki en-aut-sei=Arai en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=JoTomoyasu en-aut-sei=Jo en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoTakayuki en-aut-sei=Sato en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakuraiMasatoshi en-aut-sei=Sakurai en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=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=KataokaKeisuke en-aut-sei=Kataoka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 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=16 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=17 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=18 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=19 ORCID= en-aut-name=KatoMotohiro en-aut-sei=Kato en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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, Graduate School of Medicine, Kyoto University kn-affil= affil-num=2 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=5 en-affil=Department of Hematology, Toranomon Hospital kn-affil= affil-num=6 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University 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=Division of Clinical 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 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=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=14 en-affil=Department of Hematology, Chiba University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology, Hokkaido University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology, Osaka Metropolitan University Hospital kn-affil= affil-num=17 en-affil=Department of Hematology, Kanazawa University Hospital kn-affil= affil-num=18 en-affil=Department of Hematology, Institute of Science Tokyo Hospital 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=Department of Pediatrics, The University of Tokyo kn-affil= affil-num=21 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=22 en-affil=Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital kn-affil= en-keyword=chimeric antigen receptor T-cell therapy kn-keyword=chimeric antigen receptor T-cell therapy en-keyword=cytokine release syndrome kn-keyword=cytokine release syndrome en-keyword=estimated glomerular filtration rate kn-keyword=estimated glomerular filtration rate en-keyword=large B-cell lymphoma kn-keyword=large B-cell lymphoma END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue= article-no= start-page=148 end-page=159 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=Behavioral effects of a chronic envy-like stress paradigm in mice using an adjacent cage model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Social comparison and envy are significant psychosocial stressors in humans and are known to be involved in the onset and persistence of psychiatric disorders. However, animal models capable of experimentally reproducing the effects of indirect social comparison without physical contact are limited. In this study, we used a newly developed "adjacent-cage paradigm" to investigate whether chronic vicarious exposure to conspecifics in different environments induces envy-like stress in mice.
Methods: Male C57BL/6 N mice served as observers, while demonstrator mice were assigned to one of four conditions: (1) an environment enriched with objects, (2) an igloo, (3) a tube, or (4) social isolation. Observers were continuously exposed to these adjacent cages for 21 days. Subsequently, a comprehensive battery of behavioral tests was conducted to assess general health, anxiety-like behavior, spatial memory, social behavior, and depression-like behavior.
Results: In the objects condition, a decrease in time spent in the light compartment of the light/dark box indicated an increase in anxiety-like behavior. In the isolation condition, the mean duration per social interaction was shortened, suggesting a qualitative change in social behavior. The igloo condition resulted in reduced immobility time in the forced swim test, suggesting a possible alteration in stress coping behavior. Furthermore, increased nociceptive sensitivity was observed in the hot plate test under both the objects and isolation conditions.
Conclusion: Although the envy-like stress paradigm did not affect many behavioral indices, it did cause condition-dependent and limited behavioral changes. This suggests that the paradigm may serve as a novel model for capturing psychological and context-dependent social stress, which differs from conventional physical stress models. Elucidating the neural basis of this paradigm is expected to contribute to the understanding of how social comparison affects mental health in modern society. en-copyright= kn-copyright= en-aut-name=UenoHiroshi en-aut-sei=Ueno en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaYoshihiro en-aut-sei=Tanaka en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitanoEriko en-aut-sei=Kitano en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriSachiko en-aut-sei=Mori en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MurakamiShinji en-aut-sei=Murakami en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WaniKenta en-aut-sei=Wani en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkamotoMotoi en-aut-sei=Okamoto en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=2 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=8 en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= en-keyword=envy-like stress kn-keyword=envy-like stress en-keyword=social comparison kn-keyword=social comparison en-keyword=psychosocial stress kn-keyword=psychosocial stress en-keyword=mouse model kn-keyword=mouse model en-keyword=anxiety-like behavior kn-keyword=anxiety-like behavior END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=pcag052 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cytokinin receptor AHK3 influences leaf size by modulating trans-zeatin-type cytokinin levels in xylem en-subtitle= kn-subtitle= en-abstract= kn-abstract=Trans-zeatin (tZ)-type cytokinins (CKs) are predominantly synthesized in roots, transported to the shoot via the xylem, and coordinate diverse physiological processes in aerial organs. Within this process, the regulation of CK biosynthesis by nitrate signaling via nodule inception-like protein 7, as well as the loading of tZ-type CKs into the xylem by ATP-binding cassette transporter G14, have been well studied. However, the roles of other components remain unclear. Here, we show that CK perception and degradation in roots, as mediated by Arabidopsis histidine kinase 3 (AHK3) and CK oxidase/dehydrogenase 4 (CKX4), modulate root-to-shoot tZ-type cytokinin transport in response to nitrate. Grafting experiments demonstrate that root-specific AHK3 deficiency systemically increases the leaf blade area through long-distance signals of root-derived tZ-type CKs, perceived by shoot-expressed AHK3. Transcriptome and hormonome analyses reveal that root-specific AHK3 deficiency reduces CKX4 expression in roots, elevating tZ-type CK levels in roots and xylem sap and thereby enhancing the leaf CK response. Transfer experiments manipulating root nitrate levels show that root-specific AHK3 deficiency promotes the leaf blade area in a manner dependent on both nitrate and root-derived tZ-type CK signaling. Moreover, both nitrate signals and root-expressed AHK3 are required for maximal CKX4 induction in roots, and root-specific CKX4 deficiency enhances the leaf blade area in a nitrate-dependent manner. These findings reveal a novel mechanism in which an AHK3–CKX4 module governs xylem transport of tZ-type CKs, fine-tuning leaf size according to root nitrate status. en-copyright= kn-copyright= en-aut-name=MondenKota en-aut-sei=Monden en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiTakamasa en-aut-sei=Suzuki en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KojimaMikiko en-aut-sei=Kojima en-aut-mei=Mikiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakebayashiYumiko en-aut-sei=Takebayashi en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamiyaTakehiro en-aut-sei=Kamiya en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KibaTakatoshi en-aut-sei=Kiba en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakakibaraHitoshi en-aut-sei=Sakakibara en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakagawaTsuyoshi en-aut-sei=Nakagawa en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HachiyaTakushi en-aut-sei=Hachiya en-aut-mei=Takushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=College of Bioscience and Biotechnology, Chubu University kn-affil= affil-num=3 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=4 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=5 en-affil=Graduate School of Agricultural and Life Sciences, Tokyo University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=8 en-affil=Department of Molecular and Functional Genomics, Interdisciplinary Centerfor Science Research, Shimane University kn-affil= affil-num=9 en-affil=Department of Molecular and Functional Genomics, Interdisciplinary Centerfor Science Research, Shimane University kn-affil= en-keyword=Arabidopsis thaliana kn-keyword=Arabidopsis thaliana en-keyword=cytokinin kn-keyword=cytokinin en-keyword=micrografting kn-keyword=micrografting en-keyword=nitrate signal kn-keyword=nitrate signal en-keyword=trans-zeatin kn-keyword=trans-zeatin END start-ver=1.4 cd-journal=joma no-vol=49 cd-vols= no-issue=3 article-no= start-page=496 end-page=502 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260314 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bortezomib Induces Apoptosis via Upregulation of Abhd4 in Peripheral Nerve Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bortezomib, a first-in-class proteasome inhibitor, is widely used to treat multiple myeloma and other hematological malignancies. Despite its therapeutic efficacy, bortezomib causes peripheral neuropathy (PN) in approximately 20–30% of patients, often leading to dose reduction or discontinuation. Preventive or therapeutic approaches to bortezomib-induced PN are currently unavailable, as its precise mechanism remains unclear. In this study, we compared the effects of bortezomib and the second-generation proteasome inhibitor carfilzomib on peripheral nerve cells to identify candidate molecules involved in PN development. Transcriptome profiling of differentiated F11 cells, a hybridoma of a rat embryonic dorsal root ganglion and mouse neuroblastoma cell line N18TG2, revealed that bortezomib selectively upregulated α/β-hydrolase containing domain 4 (Abhd4), whereas carfilzomib did not. This finding was confirmed by quantitative RT-PCR and immunoblotting, which demonstrated consistent increases in Abhd4 mRNA and protein levels following bortezomib treatment. Functional analysis further revealed that Abhd4 overexpression promoted early apoptosis, suggesting a mechanistic link between bortezomib-induced Abhd4 elevation and neuronal vulnerability. Therefore, these results suggest that Abhd4 represents a candidate molecular signature associated with bortezomib-induced PN. Although further in vivo validation is needed, these findings warrant further investigation of Abhd4 as a potential contributor to bortezomib-induced PN. en-copyright= kn-copyright= en-aut-name=KonishiYusuke en-aut-sei=Konishi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OmuraTomohiro en-aut-sei=Omura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IjichiTakeshi en-aut-sei=Ijichi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=HayakawaRyunosuke en-aut-sei=Hayakawa en-aut-mei=Ryunosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=ItoharaKotaro en-aut-sei=Itohara en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=Education and Research Center for Clinical Pharmacy, Kobe Pharmaceutical University kn-affil= affil-num=6 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=7 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=8 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= en-keyword=bortezomib kn-keyword=bortezomib en-keyword=carfilzomib kn-keyword=carfilzomib en-keyword=peripheral neuropathy kn-keyword=peripheral neuropathy en-keyword=multiple myeloma kn-keyword=multiple myeloma en-keyword=proteasome inhibitor kn-keyword=proteasome inhibitor END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=3 article-no= start-page=643 end-page=650 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=Post Hoc Analysis of Frailty and Tracheostomy Risk in Older Patients Intubated and in an Intensive Care Unit in Japan: An Inverse Association in Older Patients with Advanced Age en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: This post hoc analysis of a prospectively collected intensive care unit (ICU) cohort examined the association between frailty and the likelihood of tracheostomy in older Japanese patients (aged ≥65 years). Frailty, a condition of increased vulnerability to stressors, is common among older patients in the ICU and may influence clinical decision-making and outcomes. We aimed to explore whether baseline frailty is associated with the likelihood of receiving tracheostomy in older patients in the ICUs.
Methods: We analyzed data from a multicenter prospective study conducted from November 2019 to April 2020 at 17 hospitals in Japan. Patients aged ≥65 years, admitted directly from the emergency department, and requiring mechanical ventilation, were included. After excluding early deaths (≤5 days) or treatment-limit cases, 363 patients with intubation remained. Frailty was assessed using the Clinical Frailty Scale (CFS), with primary cutoff CFS ≥4. The primary outcome was the occurrence of tracheostomy during ICU stay. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using generalized linear models with a Poisson distribution, adjusted for age, sex, Charlson Comorbidity Index, and Acute Physiology and Chronic Health Evaluation II score.
Results: Among 363 patients, patients with frailty (CFS ≥4) had a significantly lower adjusted risk of having tracheostomy than did those with less frailty (CFS <4) (adjusted RR: 0.40; 95% CI: 0.27-0.61). In patients aged ≥75 years, the adjusted RR for CFS ≥4 was 0.32 (95% CI: 0.20-0.50), indicating a pronounced reduction in tracheostomy use among patients with frailty.
Conclusions: Frailty (CFS ≥4) was independently associated with a lower likelihood of tracheostomy, particularly in patients aged ≥75 years. en-copyright= kn-copyright= en-aut-name=UmedaTakehide en-aut-sei=Umeda en-aut-mei=Takehide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HongoTakashi en-aut-sei=Hongo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InabaMototaka en-aut-sei=Inaba en-aut-mei=Mototaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=AriyasuYoshinori en-aut-sei=Ariyasu en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= affil-num=3 en-affil= kn-affil= affil-num=4 en-affil= kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil= kn-affil= en-keyword=frailty kn-keyword=frailty en-keyword=respiration kn-keyword=respiration en-keyword=tracheostomy kn-keyword=tracheostomy en-keyword=critical care outcomes kn-keyword=critical care outcomes en-keyword=aged kn-keyword=aged END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=5 article-no= start-page=e70314 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=Survey to Document the Adverse Reactions After Human Papillomavirus Vaccination Among Japanese Female Youth at a University en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim: Concerns about possible adverse events remain a critical barrier in implementing human papillomavirus (HPV) vaccination among Japanese youth. This study aimed to understand the time course of adverse events experienced by HPV vaccine recipients.
Methods: An online questionnaire survey was given to students, faculty, and staff aged 18–26 years, at Okayama University Hospital, who received the HPV vaccine. The survey gathered information on the number of HPV vaccine doses received, prevaccination health conditions, adverse reactions within 2 h and between 2 h and 7 days postvaccination, menstrual irregularities after vaccination, reasons for getting vaccinated, feelings before and after vaccination, and factors providing reassurance during vaccination. Prevalence of symptoms was expressed as numbers and percentages, and analyses were performed using Chi-squared or Fisher's exact tests.
Results: Responses were obtained from 299 participants, yielding a 75% response rate. Approximately 60% participants reported local pain, 30% swelling, and 4% fever. Most symptoms resolved on the vaccination day itself or the following day, although some persisted for 3–7 days. Over 80% participants rated their pain between 0 and 3 on numerical rating scale of 0–10. While 60% experienced anxiety before vaccination, 90% reported no anxiety afterward.
Conclusions: Our study presents one of the first comprehensive accounts of post-HPV vaccination adverse events and their time course, and underpins the importance of disseminating detailed information about vaccine-associated adverse reactions to encourage greater vaccine uptake. en-copyright= kn-copyright= en-aut-name=HiguchiChigusa en-aut-sei=Higuchi en-aut-mei=Chigusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=IwasakiYoshiaki en-aut-sei=Iwasaki en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Educational and Research Management Field, Health Management Department, Okayama University kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=1Educational and Research Management Field, Health Management Department, Okayama University kn-affil= affil-num=4 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine kn-affil= en-keyword=anxiety kn-keyword=anxiety en-keyword=human papillomavirus vaccine kn-keyword=human papillomavirus vaccine en-keyword=Japanese youth kn-keyword=Japanese youth en-keyword=questionnaire kn-keyword=questionnaire en-keyword=survey kn-keyword=survey END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=3 article-no= start-page=e105091 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Septic Arthritis of the Temporomandibular Joint Complicated by Dislocation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Septic arthritis of the temporomandibular joint (SATMJ) is a rare but potentially serious condition, and standardized diagnostic and therapeutic strategies have not been established. We present the case of a 70-year-old man who developed acute right temporomandibular joint (TMJ) pain, swelling, mandibular deviation, and inability to achieve mouth closure. Computed tomography and magnetic resonance imaging revealed right TMJ dislocation, joint effusion, degenerative changes, and anterior disc displacement with effusion. Aspiration of the joint yielded neutrophil-predominant purulent fluid, although bacterial cultures were negative. The patient was treated empirically with intravenous ceftriaxone followed by oral clindamycin and amoxicillin, resulting in rapid symptom resolution, and the dislocation spontaneously reduced without surgical intervention. No recurrence was observed during three months of follow-up. This case highlights the diagnostic challenges associated with culture-negative SATMJ, supports the role of early empirical antibiotic therapy, and suggests that chronic joint instability due to habitual dislocation may predispose the TMJ to infection. en-copyright= kn-copyright= en-aut-name=KanemotoHideka en-aut-sei=Kanemoto en-aut-mei=Hideka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=5 ORCID= affil-num=1 en-affil=Department of Oral Surgery, Kochi Health Sciences Center kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine kn-affil= en-keyword=antibiotics kn-keyword=antibiotics en-keyword=culture-negative infection kn-keyword=culture-negative infection en-keyword=joint dislocation kn-keyword=joint dislocation en-keyword=septic arthritis kn-keyword=septic arthritis en-keyword=temporomandibular joint kn-keyword=temporomandibular joint END start-ver=1.4 cd-journal=joma no-vol=38 cd-vols= no-issue=3 article-no= start-page=e70128 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260227 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effectiveness and Safety of Enteroscopy-Assisted ERP-Guided Versus EUS-Guided Pancreatic Duct Drainage for Pancreaticojejunostomy Strictures: A Multicenter Observational Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Enteroscopy-assisted endoscopic retrograde pancreatography-guided pancreatic duct drainage (eERP-PDD) and endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD) are minimally invasive alternatives to surgery for pancreaticojejunostomy stricture (PJS); however, comparative data remain limited. We compared the effectiveness and safety of these approaches and identified factors associated with technical failure.
Methods: This multicenter retrospective study included 88 patients (111 procedures) who underwent endoscopic intervention for PJS at 13 Japanese tertiary centers. We compared clinical outcomes between eERP-PDD and EUS-PDD. The primary outcome was technical success; secondary outcomes included clinical success, procedure time, and adverse events (AEs). Propensity-score overlap weighting was used to adjust for baseline differences.
Results: As initial treatment, 77 patients underwent eERP-PDD and 11 underwent EUS-PDD. After adjustment, EUS-PDD achieved higher technical success (eERP-PDD, 28% vs. EUS-PDD, 71%; p = 0.012) and clinical success (22% vs. 71%; p = 0.003), with shorter procedure time (76 min vs. 41 min; p = 0.001). AE incidence was higher with EUS-PDD before adjustment (5% vs. 27%; p = 0.039) but comparable after adjustment (7% vs. 29%; p = 0.15); all AEs resolved with conservative management. Age < 75 years, male sex, and main pancreatic duct (MPD) diameter ≥ 5 mm were independently associated with eERP-PDD failure.
Conclusions: EUS-PDD demonstrated higher technical and clinical success than eERP-PDD for PJS, with comparable safety after adjustment. An MPD diameter ≥ 5 mm was associated with eERP-PDD failure. An MPD-based algorithm is proposed: eERP-PDD for MPD < 5 mm with EUS-PDD as salvage, and EUS-PDD for MPD ≥ 5 mm. This algorithm is hypothesis-generating and requires prospective validation. en-copyright= kn-copyright= en-aut-name=OtaShogo en-aut-sei=Ota en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShiomiHideyuki en-aut-sei=Shiomi en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=KanoMasataka en-aut-sei=Kano en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimataniMasaaki en-aut-sei=Shimatani en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujitaNaoki en-aut-sei=Fujita en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KamadaHideki en-aut-sei=Kamada en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UenoSaori en-aut-sei=Ueno en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OguraTakeshi en-aut-sei=Ogura en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakenakaMamoru en-aut-sei=Takenaka en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NagaoKae en-aut-sei=Nagao en-aut-mei=Kae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SakaiArata en-aut-sei=Sakai en-aut-mei=Arata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShintaniShuhei en-aut-sei=Shintani en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=InatomiOsamu en-aut-sei=Inatomi en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KitagawaKoh en-aut-sei=Kitagawa en-aut-mei=Koh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=NakanoRyota en-aut-sei=Nakano en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KoizumiMitsuhito en-aut-sei=Koizumi en-aut-mei=Mitsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ImamuraYoshiki en-aut-sei=Imamura en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhnoAkihisa en-aut-sei=Ohno en-aut-mei=Akihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=FujimoriNao en-aut-sei=Fujimori en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=TamuraTakaaki en-aut-sei=Tamura en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MiyagaharaTsukasa en-aut-sei=Miyagahara en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=NakajimaMikio en-aut-sei=Nakajima en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KitanoMasayuki en-aut-sei=Kitano en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= affil-num=1 en-affil=Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical University kn-affil= affil-num=2 en-affil=Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical University kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center kn-affil= affil-num=6 en-affil=Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Neurology, Kagawa University kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Neurology, Kagawa University kn-affil= affil-num=9 en-affil=Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University kn-affil= affil-num=10 en-affil=Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University kn-affil= affil-num=12 en-affil=Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Shiga University of Medical Science kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Shiga University of Medical Science kn-affil= affil-num=16 en-affil=Department of Gastroenterology, Nara Medical University kn-affil= affil-num=17 en-affil=Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical University kn-affil= affil-num=18 en-affil=Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=21 en-affil=Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=22 en-affil=Second Department of Internal Medicine, Wakayama Medical University kn-affil= affil-num=23 en-affil=Department of Gastroenterology, National Hospital Organization Beppu Medical Center kn-affil= affil-num=24 en-affil=Emergency and Critical Care Center, Tokyo Metropolitan Hiroo Hospital kn-affil= affil-num=25 en-affil=Second Department of Internal Medicine, Wakayama Medical University kn-affil= en-keyword=endoscopic ultrasound-guided pancreatic duct drainage kn-keyword=endoscopic ultrasound-guided pancreatic duct drainage en-keyword=enteroscopy-assisted endoscopic retrograde pancreatography-guided pancreatic duct drainage kn-keyword=enteroscopy-assisted endoscopic retrograde pancreatography-guided pancreatic duct drainage en-keyword=main pancreatic duct diameter kn-keyword=main pancreatic duct diameter en-keyword=pancreaticojejunostomy stricture kn-keyword=pancreaticojejunostomy stricture en-keyword=propensity score overlap weighting kn-keyword=propensity score overlap weighting END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=3 article-no= start-page=100926 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=Potential Immune Microenvironment Biomarkers in SCLC: J-TAIL-2 Observational Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Effective predictors of response to atezolizumab plus carboplatin/etoposide (CE) therapy in extensive-stage SCLC (ES-SCLC) remain limited. This exploratory analysis from J-TAIL-2 aimed to identify markers of survival benefit with atezolizumab plus CE therapy in ES-SCLC.
Methods: J-TAIL-2 (ClinicalTrials.gov ID, NCT04501497) was a multicenter observational study that enrolled patients receiving atezolizumab plus CE (ES-SCLC cohort) in clinical practice in Japan per local label and treatment guidelines. In this exploratory analysis, the association of CD8+ tumor-infiltrating lymphocyte (TIL) density and SCLC subtypes (SCLC-A [ASCL1 dominant], SCLC-N [NEUROD1 dominant], SCLC-P [ASCL1/NEUROD1 double-negative with POU2F3 expression], and SCLC-O [ASCL1/NEUROD1 double-negative not otherwise specified]) with overall survival (OS) and progression-free survival (PFS) was evaluated. SCLC subtyping was performed by immunohistochemistry.
Results: SCLC samples (n = 100; data cutoff, February 3, 2023) were categorized as SCLC-A (73%), SCLC-N (16%), SCLC-P (8%), and SCLC-O (3%). Among 96 patients who received first-line atezolizumab plus CE, median age was 72 (range, 39–87) years and 81% were male. Furthermore, 56 patients were classified into the CD8+ TIL-high subgroup and 40 into the TIL-low subgroup. Median (m)PFS with atezolizumab plus CE was 6.1 months (95% confidence interval [CI]: 4.5–7.5) in the TIL-high versus 4.4 months (95% CI: 4.0–5.1) in the TIL-low subgroup (p = 0.01); mOS was 18.4 (95% CI: 11.8–not estimable) versus 10.8 months (95% CI: 7.7–16.2; p = 0.04). mOS and mPFS were not significantly different between SCLC subtypes but were numerically shorter in the SCLC-N group.
Conclusions: CD8+ TIL density is a potential biomarker of clinical benefit in ES-SCLC and may facilitate patient selection for atezolizumab combination therapy. en-copyright= kn-copyright= en-aut-name=ShirasawaMasayuki en-aut-sei=Shirasawa en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishioMakoto en-aut-sei=Nishio en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OsoegawaAtsushi en-aut-sei=Osoegawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuchiEiki en-aut-sei=Kikuchi en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KimuraHideharu en-aut-sei=Kimura en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GotoYasushi en-aut-sei=Goto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuJunichi en-aut-sei=Shimizu en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyauchiEisaku en-aut-sei=Miyauchi en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige 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=MisumiToshihiro en-aut-sei=Misumi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YatabeYasushi en-aut-sei=Yatabe en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YoshidaTatsuya en-aut-sei=Yoshida en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KashimaJumpei en-aut-sei=Kashima en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OkiMasahide en-aut-sei=Oki en-aut-mei=Masahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AshimuraHisao en-aut-sei=Ashimura en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KobayashiYuki en-aut-sei=Kobayashi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TanakaMisa en-aut-sei=Tanaka en-aut-mei=Misa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=GemmaAkihiko en-aut-sei=Gemma en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Kanazawa University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Thoracic Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Tohoku University Hospital kn-affil= affil-num=10 en-affil=Department of Thoracic Oncology, Kansai Medical University kn-affil= affil-num=11 en-affil=International University of Health and Welfare Narita Hospital kn-affil= affil-num=12 en-affil=Department of Data Science, National Cancer Center Hospital East kn-affil= affil-num=13 en-affil=Department of Diagnostic Pathology, National Cancer Center Hospital kn-affil= affil-num=14 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=15 en-affil=Department of Diagnostic Pathology, National Cancer Center Hospital kn-affil= affil-num=16 en-affil=Department of Respiratory Medicine, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=18 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=19 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=20 en-affil=Nippon Medical School kn-affil= en-keyword=Small cell kn-keyword=Small cell en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Atezolizumab kn-keyword=Atezolizumab en-keyword=Chemotherapy kn-keyword=Chemotherapy en-keyword=Immune microenvironment kn-keyword=Immune microenvironment END start-ver=1.4 cd-journal=joma no-vol=117 cd-vols= no-issue=5 article-no= start-page=1260 end-page=1272 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260227 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=TGF-β Inhibitor Potentiates Osimertinib-Induced Anti-Tumor Immunity in Egfr-Mutant Lung Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immunotherapy for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) remains challenging. We previously found that EGFR-tyrosine kinase inhibitors induced antitumor immunity but also triggered immunosuppressive cytokines, including transforming growth factor-β (TGF-β), in Egfr-mutant lung cancer. Here, we investigate whether TGF-β inhibition potentiates osimertinib-induced antitumor immunity using a syngeneic mouse model of Egfr-mutated lung cancer, with cancer cells subcutaneously transplanted into wild-type C57BL/6J mice. We evaluated the antitumor effect of the combination therapy with osimertinib and either nintedanib (an indirect TGF-β inhibitor) or vactosertib (a specific TGF-β type I receptor kinase inhibitor). Changes in the tumor microenvironment during treatment were assessed using immunohistochemical staining, western blot analysis, and flow cytometry. We found that TGF-β expression was upregulated in the tumor treated with osimertinib. Nintedanib monotherapy showed no significant antitumor effect, whereas osimertinib combined with nintedanib significantly potentiates the antitumor effect compared with osimertinib monotherapy in vivo. Crucially, no additive effect of nintedanib on osimertinib monotherapy was observed in vitro. Combination therapy with osimertinib and nintedanib significantly increased effector T cells (CD8+CD44+CD62L−) and Granzyme B+ areas and decreased CD206+ cells, while significantly decreasing TGF-β and SMAD2/3 expression. Similar effects were observed with vactosertib but not with a vascular endothelial growth factor receptor 2 inhibitor. In conclusion, combination therapy with osimertinib and TGF-β inhibitors potentiates osimertinib-induced antitumor immunity. These findings highlight a novel therapeutic strategy for EGFR-mutated NSCLC and warrant further clinical investigation. en-copyright= kn-copyright= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=TaokaMasataka en-aut-sei=Taoka en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriShunta en-aut-sei=Mori en-aut-mei=Shunta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaTakaaki en-aut-sei=Tanaka en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishimuraTomoka en-aut-sei=Nishimura en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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=10 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=11 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=12 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=13 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=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, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Center for Comprehensive Genomic 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=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital 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, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 kn-keyword=EGFR en-keyword=lung cancer kn-keyword=lung cancer en-keyword=nintedanib kn-keyword=nintedanib en-keyword=osimertinib kn-keyword=osimertinib en-keyword=TGF-β kn-keyword=TGF-β END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=3 article-no= start-page=e0339600 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Early administration of renin–angiotensin system inhibitors improves survival and cardiac remodeling in heart failure with preserved ejection fraction en-subtitle= kn-subtitle= en-abstract= kn-abstract=Heart failure with preserved ejection fraction (HFpEF) is a major cardiovascular disease that accounts for 50% of all cases of heart failure. Patients with HFpEF have limited therapeutic options because of the complex pathogenesis of this disease. Decreased nitric oxide (NO) levels and increased renin–angiotensin system (RAS) activity may be associated with HFpEF pathogenesis. However, whether soluble guanylate cyclase (sGC) stimulators and RAS inhibitors protect against HFpEF remains unclear. This study aimed to evaluate the preventive effects of RAS inhibitors captopril (Cap) and/or sacubitril/valsartan (Sac/Val) and sGC stimulator vericiguat (Ver) on HFpEF progression. HFpEF was induced in 8-week-old male Wistar rats through intake of L-arginine methyl ester and a high-fat diet. Results showed that the survival rate after 8 weeks of treatment was 100% in the normal diet (Cont group), Cap, and Sac/Val groups, whereas it was approximately 20% in the HFpEF and Ver groups. No significant differences in the left ventricular systolic function were found. In addition, histochemistry revealed that myocardial hypertrophy and interstitial fibrosis obviously increased in the HFpEF group but not in the Cap and Sac/Val groups compared with the Cont group. Furthermore, RNA sequencing analysis showed that the expression of genes related to inflammatory response, hypertrophy, and extracellular matrix–receptor interaction increased in the HFpEF group and decreased in the Cap and Sac/Val groups. In conclusion, early administration of Cap or Sac/Val may reduce the risk of developing HFpEF by inhibiting the RAS pathway rather than the NO-sGC-cGMP pathway. en-copyright= kn-copyright= en-aut-name=KonoYuka en-aut-sei=Kono en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SonodaKunihiro en-aut-sei=Sonoda en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhtakeKazuo en-aut-sei=Ohtake en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtaAkinobu en-aut-sei=Ota en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoShusei en-aut-sei=Yamamoto en-aut-mei=Shusei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakayamaHinako en-aut-sei=Nakayama en-aut-mei=Hinako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FukuokaTaketo en-aut-sei=Fukuoka en-aut-mei=Taketo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaiYuki en-aut-sei=Kawai en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TagoHaruka en-aut-sei=Tago en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeNobuhisa en-aut-sei=Watanabe en-aut-mei=Nobuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SatoIkumi en-aut-sei=Sato en-aut-mei=Ikumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HirohataSatoshi en-aut-sei=Hirohata en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KitamoriKazuya en-aut-sei=Kitamori en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=WatanabeShogo en-aut-sei=Watanabe en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Collage of Human Life and Environment, Kinjo Gakuin University kn-affil= affil-num=3 en-affil=School of Pharmacy, Faculty of Pharmaceutical Science, Josai University kn-affil= affil-num=4 en-affil=Collage of Human Life and Environment, Kinjo Gakuin University kn-affil= affil-num=5 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=11 en-affil=Academic Field of Health Science, Okayama University kn-affil= affil-num=12 en-affil=Academic Field of Health Science, Okayama University kn-affil= affil-num=13 en-affil=Collage of Human Life and Environment, Kinjo Gakuin University kn-affil= affil-num=14 en-affil=Academic Field of Health Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue= article-no= start-page=1759690 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260309 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of a generative AI agent for family support in implementing family-based treatment for children and adolescents with anorexia nervosa en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Family-based treatment (FBT) is a first-line psychotherapy for children and adolescents with anorexia nervosa (AN). However, families must understand the principles of FBT, provide meal support, and manage their children's pathological behaviors. Difficulties occur outside clinic hours when it is impossible to consult professionals. This “support gap” increases caregivers’ psychological distress and threatens their treatment continuity. To the best of our knowledge, this is the first domain-specific generative artificial intelligence (AI) agent designed to provide situation-specific, FBT-concordant advice and psychological support.
Methods: The system integrates three components: (1) an FBT-specific knowledge base constructed from treatment manuals, family guides, guideline-compliant resources, and a clinical Q&A corpus; (2) a multistage natural language processing pipeline using Retrieval-Augmented Generation (RAG), with intent and sentiment analyses; and (3) safety guardrails that prohibit unsolicited numerical goals or direct hospitalization recommendations and standardized escalation to clinicians. When strong negative emotions are detected, empowerment messages are dynamically incorporated to maintain caregivers’ confidence. Six clinicians with expertise with pediatric mental health authored queries that simulated common FBT-related concerns and evaluated each response for clinical appropriateness and safety, and classified problems as information insufficiency, not FBT concordant, or escalation insufficiency.
Results: Of the 477 queries, 57.0% were FBT-related, 24.5% were general AN, 16.5% were parental psychological distress, and 1.8% were related to other topics. The clinically appropriate response rate was 91.6% (437/477), including 92.3% for FBT-related questions, 88.0% for general knowledge, 93.7% for psychological distress, and 100.0% for other questions. Clinically inappropriate responses (8.4%) were mainly attributable to information insufficiency; not FBT concordant (1.8% of FBT-related responses) and escalation insufficiency (0.6% of all dialogs) rarely occurred.
Discussion: In this expert review, the safety-gated RAG system predominantly generated FBT-concordant responses that provided meal-level guidance and empathic empowerment-oriented support to families. By proceduralizing complex FBT concepts and presenting multiple response options for pathological behaviors, the system translates FBT principles into practical guidance supporting refeeding adherence, preserving family self-efficacy, and suggesting that domain-specific AI may help bridge structural limitations in FBT. Usability studies and randomized controlled trials are warranted to determine their impact on caregiver burden, self-efficacy, treatment adherence, and clinical outcomes. en-copyright= kn-copyright= en-aut-name=HanzawaMana en-aut-sei=Hanzawa en-aut-mei=Mana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkadaAyumi en-aut-sei=Okada en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaChie en-aut-sei=Tanaka en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShigeyasuYoshie en-aut-sei=Shigeyasu en-aut-mei=Yoshie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiiChikako en-aut-sei=Fujii en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HoriuchiMakiko en-aut-sei=Horiuchi en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiharaAkiko en-aut-sei=Sugihara en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakeuchiKoichi en-aut-sei=Takeuchi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakaharaRyuichi en-aut-sei=Nakahara en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatayamaHideki en-aut-sei=Katayama en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Hospital Medical Center for Children kn-affil= affil-num=2 en-affil=Department of Medical Informatics and Clinical Support Technology Development, Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital Medical Center for Children kn-affil= affil-num=4 en-affil=Department of Pediatrics, Okayama University Hospital Medical Center for Children kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama University Hospital Medical Center for Children kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Hospital Medical Center for Children kn-affil= affil-num=7 en-affil=Clinical Psychology Section, Department of Medical Support, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pediatrics, Okayama University Hospital Medical Center for Children kn-affil= affil-num=9 en-affil=Life Natural Science and Technology, Graduate School of Environmental, Okayama University kn-affil= affil-num=10 en-affil=Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Palliative and Supportive Care, Okayama University Hospital kn-affil= affil-num=12 en-affil=NEC Corporation kn-affil= affil-num=13 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Pediatrics, Okayama University Hospital Medical Center for Children kn-affil= en-keyword=anorexia nervosa kn-keyword=anorexia nervosa en-keyword=caregiver burden kn-keyword=caregiver burden en-keyword=family support kn-keyword=family support en-keyword=family-based treatment kn-keyword=family-based treatment en-keyword=generative AI agent kn-keyword=generative AI agent en-keyword=large language model kn-keyword=large language model en-keyword=retrieval-augmented generation kn-keyword=retrieval-augmented generation END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Unraveling the structural features of Dion–Jacobson-type layered perovskite-related material HCa2Nb3O10·1.5H2O en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hydrated layered oxides are widely encountered, yet the presence of disordered interlayer water often complicates crystal structure determination from laboratory X-ray diffraction. Here, we report the crystal structure of the Dion–Jacobson-type layered perovskite-related material HCa2Nb3O10·1.5H2O, solved from synchrotron X-ray diffraction data by combining direct methods in reciprocal space, Le Bail whole-pattern fitting, and Rietveld refinement. The hydrate crystallizes in a tetragonal structure with space group P42212 (a = 7.7070(5) Å, c = 32.4870(3) Å). Incorporation of partially occupied interlayer water-oxygen sites on the (110) plane at z = 0 and 1/2 successfully reproduces the low-angle 00l reflections while preserving the Ca2Nb3O10 framework. The resulting crystallographic model explicitly resolves the arrangement of interlayer water molecules and provides a robust structural foundation for band-structure calculations as well as for the rational design of hydration-controlled intercalation, exfoliation, and composite materials based on layered perovskite-related materials. en-copyright= kn-copyright= en-aut-name=ZhangZihao en-aut-sei=Zhang en-aut-mei=Zihao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanoJun en-aut-sei=Kano en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoritaShu en-aut-sei=Morita en-aut-mei=Shu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShimokawaHiromu en-aut-sei=Shimokawa en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OsadaMinoru en-aut-sei=Osada en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Institute of Materials and Systems for Sustainability (IMaSS), Nagoya 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=Department of Materials Chemistry and Institute of Materials and Systems for Sustainability (IMaSS), Nagoya University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=408 cd-vols= no-issue= article-no= start-page=117938 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=Tip position estimation of a 3-DOF soft mechanism using artificial muscles with optical fibers en-subtitle= kn-subtitle= en-abstract= kn-abstract=McKibben-type pneumatic artificial muscles (PAMs) are lightweight and flexible soft actuators with a high power-to-weight ratio, and have been widely applied to rehabilitation devices, power-assist systems, and soft robotic mechanisms. By integrating sensing functions into PAMs, their usability and controllability can be enhanced, enabling the development of more practical and advanced soft mechanisms. We previously proposed a smart artificial muscle (SAM) by integrating an optical fiber into the braided sleeve of a McKibben-type PAM, which enables displacement estimation by measuring optical bending loss. The SAM is compatible with conventional PAM fabrication processes; however, the sensor output exhibits strong nonlinearity and time dependency. In this study, an LSTM-based state estimation framework is extended from a single SAM to a three-degree-of-freedom soft mechanism composed of multiple SAMs, where strong nonlinear coupling and mutual interference arise among actuators. In the proposed framework, the LSTM model jointly processes time-series data of multi-channel optical sensor outputs and applied pressures of the three SAMs, along with past estimated states as inputs. This structure enables the model to capture nonlinear coupling, hysteresis, and time-dependent behavior, allowing estimation of the tip position of the soft mechanism. Experimental results demonstrate that the proposed method accurately captures complex nonlinear dynamics and mutual mechanical interference among multiple SAMs, achieving accurate tip position estimation. These results indicate that SAMs with integrated sensing and actuation capabilities, combined with machine-learning-based estimation, provide an effective approach for state estimation of multi-DOF soft robotic mechanisms. en-copyright= kn-copyright= en-aut-name=OkadaRikimaru en-aut-sei=Okada en-aut-mei=Rikimaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WakimotoShuichi en-aut-sei=Wakimoto en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TodaYuichiro en-aut-sei=Toda en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiuraShun en-aut-sei=Miura en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamaguchiDaisuke en-aut-sei=Yamaguchi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KandaTakefumi en-aut-sei=Kanda en-aut-mei=Takefumi 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=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Pneumatic artificial muscle kn-keyword=Pneumatic artificial muscle en-keyword=Smart artificial muscle kn-keyword=Smart artificial muscle en-keyword=Soft mechanism kn-keyword=Soft mechanism en-keyword=State estimation kn-keyword=State estimation en-keyword=Long short-term memory kn-keyword=Long short-term memory END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=5 article-no= start-page=530 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260428 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Photosynthetic Response of Larix gmelinii var. japonica Saplings After Exogenous Glutathione Foliar Application en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sapling survival and growth depend on photosynthetic assimilates. Therefore, improving physiological performance during early stages may enhance subsequent performance and nursery production. This study evaluated whether exogenous oxidized glutathione (GSSG), reported to enhance photosynthesis, improves the photosynthetic, physiological, and growth-related traits of Larix gmelinii var. japonica saplings. Sixteen saplings were assigned to four treatments: GSSG, 5-aminolevulinic acid, Hyponex, and a water control. Photosynthetic, nitrogen-related, and growth traits were measured before treatment and at 3, 6, 13, and 31 days after treatment, and biomass was assessed after three months. The GSSG treatment showed no difference in the net CO2 assimilation rate (Amax) compared with the control, but exhibited a significantly earlier peak at 6 days than the other treatments. This response was supported by the stability of GSSG-treated saplings against photoinhibition (Fv/Fm) and a tendency toward greater resilience to midday light stress (ΦPSII). Enhanced photosynthetic performance was associated with reduced carbon and nitrogen fluctuations and was accompanied by numerically greater root and stem biomass in the 2024 terminal shoots. Although fertilization effects were generally weak and transient, GSSG elicited notable responses, suggesting that the immediate enhancement of photosynthesis underlies its impact. However, its antioxidant properties under stressful conditions warrant further investigation. en-copyright= kn-copyright= en-aut-name=RahayuResa Sri en-aut-sei=Rahayu en-aut-mei=Resa Sri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshizukaWataru en-aut-sei=Ishizuka en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NaritaAyu en-aut-sei=Narita en-aut-mei=Ayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyataRie en-aut-sei=Miyata en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=KonHirokazu en-aut-sei=Kon en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyazakiYuko en-aut-sei=Miyazaki en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil= Forestry Research Institute, Hokkaido Research Organization kn-affil= affil-num=3 en-affil= Forestry Research Institute, Hokkaido Research Organization kn-affil= affil-num=4 en-affil= Forestry Research Institute, Hokkaido Research Organization kn-affil= affil-num=5 en-affil= Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil= Forestry Research Institute, Hokkaido Research Organization kn-affil= affil-num=7 en-affil= Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=exogenous glutathione kn-keyword=exogenous glutathione en-keyword=foliar fertilizer kn-keyword=foliar fertilizer en-keyword=Larix gmelinii var. japonica kn-keyword=Larix gmelinii var. japonica en-keyword=photosystem II quantum yield kn-keyword=photosystem II quantum yield en-keyword=photosynthetic rate kn-keyword=photosynthetic rate END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=181 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=Hypernatremia during the first week of life in very preterm infants and neurodevelopmental outcomes at 3 to 4 years of age: a cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Hypernatremia is a common electrolyte disorder in both term and preterm infants. Previous studies have suggested a correlation between hypernatremia and short-term complications in preterm infants, such as intraventricular hemorrhage and chronic lung disease. However, the relationship between hypernatremia and neurodevelopmental outcomes is less well understood. This study aimed to assess the association between hypernatremia during the first week of life and neurodevelopmental outcomes at 3–4 years of age in very preterm infants.
Methods This single-center, retrospective cohort study analyzed data from preterm infants born at less than 32 weeks of gestation between 2010 and 2020. Infants with peak whole blood sodium levels > 145 mEq/L during the first week of life were included in the hypernatremia group and those with ≤ 145 mEq/L in the non-hypernatremia group. The primary outcome was neurodevelopmental impairment (NDI) at 3–4 years of age, defined as developmental impairment (developmental quotient < 70), cerebral palsy, hearing impairment, or visual impairment. Secondary outcomes were the components of the primary outcome. We conducted Poisson regression analyses with robust variance, adjusting for perinatal confounders.
Results Of 272 infants with neurodevelopmental data, 82 and 190 infants were in the hypernatremia and non-hypernatremia groups, respectively. The median (interquartile range) gestational age and birth weight were 26.4 (25.1–28.0) and 28.7 (26.6–30.3) weeks and 860 (670–1062) and 997 (778–1264) g for infants in the hypernatremia and non-hypernatremia groups, respectively. Infants in the hypernatremia group had a greater incidence of NDI (29.3% vs. 14.7%, adjusted risk ratio [RR] 1.75, 95% CI 1.08–2.84) and cerebral palsy (8.5% vs. 1.6%, adjusted RR 5.5, 95% CI 1.72–17.63) than those in the non-hypernatremia group.
Conclusions Hypernatremia during the first week of life was associated with an increased risk of NDI at 3–4 years of age in very preterm infants. en-copyright= kn-copyright= en-aut-name=MurakamiMichiko en-aut-sei=Murakami en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TamaiKei en-aut-sei=Tamai en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=TakeuchiAkihito en-aut-sei=Takeuchi en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraMakoto en-aut-sei=Nakamura en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=KageyamaMisao en-aut-sei=Kageyama en-aut-mei=Misao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Division of Neonatology, NHO Okayama Medical Center 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=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Division of Neonatology, NHO Okayama Medical Center kn-affil= affil-num=5 en-affil=Division of Neonatology, NHO Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Division of Neonatology, NHO Okayama Medical Center kn-affil= en-keyword=Hypernatremia kn-keyword=Hypernatremia en-keyword=Development kn-keyword=Development en-keyword=Very preterm kn-keyword=Very preterm en-keyword=Cerebral palsy kn-keyword=Cerebral palsy END start-ver=1.4 cd-journal=joma no-vol=40 cd-vols= no-issue=6 article-no= start-page=e70582 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260528 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Risk Factors for Waiting List Mortality in Lung Transplant Candidates With Post‐Hematopoietic Stem Cell Transplantation Non‐Infectious Pulmonary Complications en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Late-onset non-infectious pulmonary complications (LONIPCs) following hematopoietic stem cell transplantation (HSCT) are a known indication for need of lung transplantation. This study aimed to clarify the clinical characteristics of patients with LONIPCs after HSCT who were registered for lung transplantation and reveal the risk factors for waiting list mortality.
Methods: We retrospectively reviewed the clinical data of patients with LONIPCs after allogeneic HSCT who were referred to Okayama University Hospital and registered in the Japan Organ Transplant Network for deceased-donor lung transplantation between 2005 and 2023. Pediatric patients aged <18 years at the time of registration were excluded.
Results: Thirty-four patients were included in this study. Notably, two distinct phenotypic groups were identified: One with a bronchiolitis obliterans pattern on high-resolution computed tomography and a mixed ventilatory defect, and the other with a pleuroparenchymal fibroelastosis pattern and a restrictive ventilatory defect. The median waiting duration for a deceased-donor lung transplant was 662 days, and 16 patients died during the waiting period. The cumulative incidence of waiting list mortality was 20.6% (95% confidence interval [CI], 8.9%–35.6%) at 1 year and 46.1% (95% CI, 27.8%–62.7%) at 3 years. A history of pneumothorax, greater dyspnea on exertion, and higher serum Krebs von den Lungen-6 levels were associated with an increased risk of waiting list mortality.
Conclusion: In patients with LONIPCs after HSCT, a history of pneumothorax may be a marker of a poor prognosis and could serve as a criterion for referral of lung transplantation. en-copyright= kn-copyright= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SenooSatoru en-aut-sei=Senoo en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MakimotoSatoko en-aut-sei=Makimoto en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaganoTomohiro en-aut-sei=Nagano en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=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= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=Department of Radiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=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= en-keyword=hematopoietic stem cell transplantation kn-keyword=hematopoietic stem cell transplantation en-keyword=late-onset non-infectious pulmonary complications kn-keyword=late-onset non-infectious pulmonary complications en-keyword=lung transplantation kn-keyword=lung transplantation en-keyword=pneumothorax kn-keyword=pneumothorax END start-ver=1.4 cd-journal=joma no-vol=53 cd-vols= no-issue=3 article-no= start-page=e2025GL118991 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260129 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sound Velocities of FeO‐Bearing Ringwoodite and Majorite: Implication for Martian Mantle Seismic Profiles en-subtitle= kn-subtitle= en-abstract= kn-abstract=Compressional and shear wave velocities (Vp, Vs) of candidate Martian deep-mantle minerals, FeO-rich ringwoodite ((Mg0.66Fe0.34)2SiO4) and majorite (Mg0.75Fe0.10Al0.26Ca0.07Si0.84O3), were measured up to 25 GPa and 700 K using Brillouin light scattering coupled with externally-heated diamond anvil cells. Thermoelastic modeling of our results and literature data along a representative areotherm showed that Vp and Vs of FeO-bearing ringwoodite are approximately 7.5% and 11.0% higher than that of the majorite. Our results reveal that velocity profiles of these Martian deep-mantle minerals are more sensitive to variations in the ringwoodite/majorite (Mg/Si) ratio than to thermal and FeO chemical perturbations. Our best-fit velocity model to a recent seismic model by Samuel et al. (2023, https://doi.org/10.1038/s41586-023-06601-8) indicates the Martian mantle contains approximately 67 vol.% ringwoodite and 33 vol.% majorite, suggesting a ringwoodite-rich aggregate in the Martian lowermost solid mantle. The ringwoodite-majorite mantle likely co-evolved with the FeO and other incompatible elements in the molten silicate layer above the Martian core-mantle boundary. en-copyright= kn-copyright= en-aut-name=LiLuo en-aut-sei=Li en-aut-mei=Luo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RyuYoung Jay en-aut-sei=Ryu en-aut-mei=Young Jay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhangDongzhou en-aut-sei=Zhang en-aut-mei=Dongzhou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CharitonStella en-aut-sei=Chariton en-aut-mei=Stella kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=PrakapenkaVitali B. en-aut-sei=Prakapenka en-aut-mei=Vitali B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LinJung‐Fu en-aut-sei=Lin en-aut-mei=Jung‐Fu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Earth and Planetary Sciences, Jackson School of Geosciences, The University of Texas at Austin kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=GeoSoilEnviroCARS, University of Chicago kn-affil= affil-num=4 en-affil=GeoSoilEnviroCARS, University of Chicago kn-affil= affil-num=5 en-affil=GeoSoilEnviroCARS, University of Chicago kn-affil= affil-num=6 en-affil=GeoSoilEnviroCARS, University of Chicago kn-affil= affil-num=7 en-affil=Department of Earth and Planetary Sciences, Jackson School of Geosciences, The University of Texas at Austin kn-affil= en-keyword=sound velocity kn-keyword=sound velocity en-keyword=ringwoodite kn-keyword=ringwoodite en-keyword=majorite kn-keyword=majorite en-keyword=Martian mantle kn-keyword=Martian mantle en-keyword=FeO-rich kn-keyword=FeO-rich END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=3 article-no= start-page=86 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=Immediate and delayed effects of thermal stress on fever-associated seizures in children: A time-stratified case-crossover study in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study aimed to examine the non-linear and delayed effects of thermal stress, measured by the hourly Universal Thermal Climate Index (UTCI), on the risk of pediatric fever-associated seizures (FAS). We conducted a time-stratified case-crossover study in Okayama, Japan (May 2015–March 2023), analyzing 3,201 ambulance-attended FAS cases in children younger than 7 years. Using a distributed lag non-linear model (DLNM) with a 144-h lag, we estimated the association between UTCI and FAS. The analysis revealed a bimodal exposure–response relationship. Moderate Cold Stress (10th percentile, –1.6 °C) was associated with a significant cumulative odds ratio (OR) of 2.22 (95% CI: 1.22–4.06). Risk also increased at the upper range of No Thermal Stress (24.2 °C; cumulative OR 2.74, 95% CI: 1.63–4.63), extending into Moderate Heat Stress (28.7 °C; cumulative OR 2.26, 95% CI: 1.33–3.84). These effects were primarily delayed to 72–96 h for Moderate Cold and reached a peak around 100 h for Moderate Heat. Strong Heat Stress showed immediate but non-significant risk patterns. These findings suggest that infection-mediated pathways likely drive the observed bimodal risk pattern, demonstrate the utility of high-resolution bioclimatic indices, and can inform the development of temperature-specific public health alerts. en-copyright= kn-copyright= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamuraYuka en-aut-sei=Yamamura en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UraguchiKensuke en-aut-sei=Uraguchi en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 ORCID= affil-num=1 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Time-stratified Case-crossover study kn-keyword=Time-stratified Case-crossover study en-keyword=Thermal stress kn-keyword=Thermal stress en-keyword=Fever-associated seizures kn-keyword=Fever-associated seizures en-keyword=Universal Thermal Climate Index (UTCI) kn-keyword=Universal Thermal Climate Index (UTCI) en-keyword=Climate change kn-keyword=Climate change en-keyword=Pediatric emergency kn-keyword=Pediatric emergency END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=骨骼筋再生における筋衞星細胞TRPV2の役割 kn-title=TRPV2 in muscle satellite cells is crucial for skeletal muscle remodelling　 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=CHENYANZHU en-aut-sei=CHEN en-aut-mei=YANZHU kn-aut-name=陈彦竹 kn-aut-sei=陈 kn-aut-mei=彦竹 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=p53搭載腫瘍溶解アデノウイルスは、マクロピノサイトーシスを介して膵癌関連膵星細胞にアポトーシスを誘導する　 kn-title=p53-armed oncolytic adenovirus induces apoptosis in pancreatic cancer-associated stellate cells via macropinocytosis en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NISHIYAMATakeyoshi en-aut-sei=NISHIYAMA en-aut-mei=Takeyoshi kn-aut-name=西山岳芳 kn-aut-sei=西山 kn-aut-mei=岳芳 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=疾病負担の長期的な傾向を明らかにするため、グローバル疾病負担研究2019および世界保健機関死亡データベースを用いた世界レベル、地域レベル、国レベルにおける国際疫学研究 kn-title=Long-term trends in disease burden at global, regional, and national levels: findings from the Global Burden of Disease Study 2019 and the World Health Organization Mortality Database en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=VU THI QUYNH en-aut-sei=VU THI QUYNH en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=口腔扁平上皮癌におけるNeurokinin 3 Receptorの機能的役割とFezolinetantの抗腫瘍効果の検討 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=FUKUSHIMAKiho en-aut-sei=FUKUSHIMA en-aut-mei=Kiho kn-aut-name=福嶋輝保 kn-aut-sei=福嶋 kn-aut-mei=輝保 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=cr.26-0288 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=Tailored Management of Anomalous Systemic Arterial Supply to the Basal Segment of the Lung: A Case Report and Literature Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=INTRODUCTION: Parenchyma-preserving strategies for anomalous systemic arterial supply to the basal segment of the lung have gained increasing attention. However, pulmonary infarction of the preserved lung has been reported, and clear criteria for selecting the optimal treatment have yet to be established. We report 2 cases in which detailed preoperative imaging informed tailored management—right posterior basal segmentectomy in 1 patient and endovascular embolization of the aberrant artery in the other—both without postoperative complications. A review of the relevant literature is also provided, with an emphasis on potential selection criteria.
CASE PRESENTATION: Case 1: A 20-year-old asymptomatic woman was referred after an abnormal screening chest radiograph. CT demonstrated an aberrant artery arising from the abdominal aorta supplying the right posterior basal segment (S10) with a large intravascular thrombus. The pulmonary artery showed hypoplasia limited to A10, while the other branches were normal, and no parenchymal congestion was identified. Following resection of the aberrant artery, robot-assisted right S10 segmentectomy was performed. The postoperative course was uneventful, and the patient was discharged on POD 6. Case 2: A 27-year-old woman was incidentally diagnosed on CT for an unrelated indication. An aberrant artery arising from the descending thoracic aorta supplied the left basal segment. Pulmonary arterial branches were preserved, with only minimal congestion in S9-10. Angiography revealed no evidence of an arteriovenous fistula. As surgical lung resection was considered unnecessary, coil embolization of the aberrant artery was performed. No complications occurred, and the patient was discharged on day 3 after the procedure.
CONCLUSIONS: In patients with anomalous systemic arterial supply to the basal segment of the lung, when pulmonary arterial branches are preserved and background parenchymal congestion is minimal, parenchyma-sparing approaches should be considered. en-copyright= kn-copyright= en-aut-name=MoriShunsuke en-aut-sei=Mori en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomitaKoji en-aut-sei=Tomita en-aut-mei=Koji 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=NakajimaKumi en-aut-sei=Nakajima en-aut-mei=Kumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=TorigoeHidejiro en-aut-sei=Torigoe en-aut-mei=Hidejiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=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= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=anomalous systemic arterial supply kn-keyword=anomalous systemic arterial supply en-keyword=basal lung segment kn-keyword=basal lung segment en-keyword=segmentectomy kn-keyword=segmentectomy en-keyword=endovascular embolization kn-keyword=endovascular embolization en-keyword=pulmonary infarction kn-keyword=pulmonary infarction END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=1 article-no= start-page=105 end-page=119 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=Programmable synthesis of alkaloidal frameworks integrating Michael acceptor generates covalent probes for targeting POLE3 in HBV replication en-subtitle= kn-subtitle= en-abstract= kn-abstract=The growing need for effective HBV treatments and lead compounds with novel mechanisms prompted us to explore synthetic strategies for generating skeletally diverse alkaloidal Michael acceptors. Our approach uniquely embeds Michael acceptors directly within multicyclic alkaloid-inspired frameworks, exploiting the azepinoindole scaffold—a privileged structure in indole alkaloids. A single-step assembly between the versatile intermediate 13 with methyl propiolate 14 or its derivatives enabled the rapid and divergent synthesis of six alkaloidal Michael acceptors (15–20). This strategy facilitated systematic diversification of three-dimensional functional group arrangements and precise tuning of the electronic and steric properties of the embedded α,β-unsaturated carbonyl moieties. The optimal hit 15 inhibited hepatitis B surface antigen (HBsAg) production with an IC50 of 2.48 μM and significantly reduced levels of covalently closed circular DNA (cccDNA), the master template of HBV. Unlike existing nucleoside/nucleotide-based anti-HBV drugs that primarily inhibit reverse transcription, the alkaloidal Michael acceptor 15 suppressed both cccDNA and relaxed circular DNA (rcDNA) levels, suggesting a potential pathway toward a functional HBV cure. Our study also streamlined the target identification by leveraging the covalent binding properties of the Michael acceptors and the operational simplicity of biotin- or fluorescent-tag attachment via a pre-installed alkyne moiety. Competitive pull-down experiments identified several potential target proteins, involving DNA polymerase epsilon subunit 3 (POLE3). Notably, the alkaloidal Michael acceptor 15 was demonstrated to covalently modify Cys51 in POLE3, providing new insights into virus–host interactions and opening novel avenues for targeted anti-HBV therapies. This approach represents a significant advance beyond traditional screening methods and underscores the potential of skeletally diverse alkaloidal Michael acceptors in antiviral drug development. en-copyright= kn-copyright= en-aut-name=KanekoNobuto en-aut-sei=Kaneko en-aut-mei=Nobuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HimenoMisao en-aut-sei=Himeno en-aut-mei=Misao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiYuhi en-aut-sei=Kobayashi en-aut-mei=Yuhi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanifujiRyo en-aut-sei=Tanifuji en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KubotaHiroki en-aut-sei=Kubota en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MizoguchiHaruki en-aut-sei=Mizoguchi en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MuroiMakoto en-aut-sei=Muroi en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SuzukiTakehiro en-aut-sei=Suzuki en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugiyamaMasaya en-aut-sei=Sugiyama en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=DohmaeNaoshi en-aut-sei=Dohmae en-aut-mei=Naoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OsadaHiroyuki en-aut-sei=Osada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KidoTaketomo en-aut-sei=Kido en-aut-mei=Taketomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MiyajimaAtsushi en-aut-sei=Miyajima en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OguriHiroki en-aut-sei=Oguri en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Science, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Developmental Medical Sciences, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Chemistry, Graduate School of Science, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Chemistry, Graduate School of Science, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology kn-affil= affil-num=6 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Centre for Sustainable Resource Science, RIKEN kn-affil= affil-num=8 en-affil=Centre for Sustainable Resource Science, RIKEN kn-affil= affil-num=9 en-affil=Department of Viral Pathogenesis and Control, National Institute of Global Health and Medicine, Japan Institute for Health Security kn-affil= affil-num=10 en-affil=Centre for Sustainable Resource Science, RIKEN kn-affil= affil-num=11 en-affil=Centre for Sustainable Resource Science, RIKEN kn-affil= affil-num=12 en-affil=Laboratory of Cell Growth and Differentiation, Institute for Quantitative Biosciences, The University of Tokyo kn-affil= affil-num=13 en-affil=Laboratory of Cell Growth and Differentiation, Institute for Quantitative Biosciences, The University of Tokyo kn-affil= affil-num=14 en-affil=Department of Chemistry, Graduate School of Science, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue= article-no= start-page=9 end-page=20 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260531 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=見方・考え方で学びと思考をつなぐ教授法 数学的な見方・考え方により数学的活動と思考を融合する en-subtitle= kn-subtitle= en-abstract= kn-abstract=　「個別最適な学び」「協働的な学び」の提案に注目が集まっている。これらは全教科教育に当てはまることである。これらを算数の改革・改善の喫緊の課題のように主張するする人が多い。本当の課題は大局的に改訂された算数・数学の資質・能力（2017）の育成にあると考える。「主体的・対話的で深い学び」に重点を置く授業公開を見ることが流行している。ところが、「主体的で、対話的な深い学び」を、資質・能力と結びつけた事例研究は見られない。「数学的に考える」を育成するには、「数学的な見方・考え方」と「数学的活動」を3者一体的に連動させるべきである。この理念は教材構成、授業構成まで具体化されていない。そこで、具体的にどのようにシステムを構想すればよいのか､その一端を検討する。 en-copyright= kn-copyright= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=黒﨑東洋郎 kn-aut-sei=黒﨑 kn-aut-mei=東洋郎 aut-affil-num=1 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=森川唯 kn-aut-sei=森川 kn-aut-mei=唯 aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=岡山大学名誉教授 affil-num=2 en-affil= kn-affil=倉敷市立玉島南小学校 en-keyword=数学的な見方・考え方 kn-keyword=数学的な見方・考え方 en-keyword=数学的活動 kn-keyword=数学的活動 en-keyword=数学的に考える kn-keyword=数学的に考える en-keyword=連鎖 kn-keyword=連鎖 END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260531 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=巻頭⾔ en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=中川征樹 kn-aut-sei=中川 kn-aut-mei=征樹 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡⼭⼤学算数・数学教育学会 END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=3 article-no= start-page=921 end-page=930 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260520 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Verification of Relationship Between Multiplicatively Weighted Voronoi Diagram and Huff Model: A Case Study on Order Assignment in E-Commerce en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study examines the relationship between a multiplicatively weighted (MW-) Voronoi diagram and the Huff model. A mathematical comparison demonstrates that the models are structurally equivalent when the Huff model is deterministic and the distance decay parameter λ takes a specific value. This theoretical finding was empirically validated using real-world e-commerce order assignment data. The experiments demonstrate the distinct strengths of each model. The Huff model enables the flexible balancing of competing objectives through parameter adjustment, whereas the MW-Voronoi diagram provides geometric clarity in the interpretation of territories. We conclude that the selection of the two models should be guided by the problem objectives, depending on whether probabilistic flexibility or deterministic spatial partitioning is required. en-copyright= kn-copyright= en-aut-name=KawamotoTakaki en-aut-sei=Kawamoto en-aut-mei=Takaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HasuikeTakashi en-aut-sei=Hasuike en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Industrial and Management Systems Engineering, School of Creative Science and Engineering, Waseda University kn-affil= en-keyword=multiplicatively weighted Voronoi diagram kn-keyword=multiplicatively weighted Voronoi diagram en-keyword=Huff model kn-keyword=Huff model en-keyword=order assignment algorithm kn-keyword=order assignment algorithm END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=1 article-no= start-page=ra.2025-0153 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=Current Status of Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: An International Perspective Including Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Middle meningeal artery embolization (MMAE) for chronic subdural hematoma (CSDH) is gaining global prevalence as a minimally invasive treatment aimed at serving as an adjunct to or method of avoiding surgery; however, its optimal positioning remains unclear. This study outlines the current status of MMAE in Japan, Germany, and the United States based on nationwide survey reports, recently published consensus guidelines, and meta-analyses including randomized controlled trials (RCTs) reported in the New England Journal of Medicine (NEJM; EMBOLISE, STEM, and MAGIC-MT) and examines its efficacy and limitations. Real-world clinical data from Japan, Germany, and the United States indicate that MMAE is primarily used as an adjunctive therapy following surgery for older and high-risk or recurrent cases, or as a stand-alone therapy in selected cases to safely reduce the risk of recurrence and reoperation. While a multidisciplinary consensus statement takes a cautious stance that limits MMAE to recurrent or inoperable cases such as those at high risk associated with interrupting antithrombotic medication, the Society of Vascular and Interventional Neurology guidelines published after the RCTs strongly recommend the concurrent use of MMAE with standard therapy in de novo cases. Meta-analyses integrating the 3 NEJM trials and other RCTs showed that MMAE suppressed recurrence and reoperation versus standard treatment, with particularly pronounced effects in the nonsurgical (conservative treatment) group; however, the additive effect was limited in the surgical adjunct group. No improvement in functional outcomes (modified Rankin Scale score) was observed. Cost-effectiveness analyses suggest that, while MMAE reduces reoperations, routine implementation for all cases is difficult to justify economically because of high procedural costs, indicating the need to narrow the indication to populations at high risk of recurrence. In conclusion, although MMAE is an effective treatment option, the current evidence does not support its uniform introduction in all patients with CSDH. Thus, it is necessary to individualize and adapt the indications for specific patient subgroups, such as those at high risk of recurrence or those for whom surgery is difficult. Finally, we propose a pragmatic treatment strategy for MMAE stratified by disease stage (de novo vs. recurrent) and clinical severity to guide the individualized selection of adjunctive and stand-alone embolization. en-copyright= kn-copyright= en-aut-name=KawakamiMasato en-aut-sei=Kawakami en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugiuKenji en-aut-sei=Sugiu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiramatsuMasafumi en-aut-sei=Hiramatsu en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=KimuraRyu en-aut-sei=Kimura en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SoutomeYuta en-aut-sei=Soutome en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujitaJuntaro en-aut-sei=Fujita en-aut-mei=Juntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HirataYuichi en-aut-sei=Hirata en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BabaFukiko en-aut-sei=Baba en-aut-mei=Fukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=middle meningeal artery embolization kn-keyword=middle meningeal artery embolization en-keyword=chronic subdural hematoma kn-keyword=chronic subdural hematoma en-keyword=current status kn-keyword=current status END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=48 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Adverse events of romidepsin versus tucidinostat for peripheral T-cell lymphoma: a pharmacovigilance study using the Japanese adverse drug event report database en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of lymphomas with poor prognosis, particularly in patients with relapsed or refractory (R/R) disease. Romidepsin and tucidinostat are histone deacetylase inhibitors used to treat R/R PTCL. No head-to-head post-marketing surveillance studies have compared adverse events (AEs) between the two agents. In this brief report, the AE profiles of romidepsin and tucidinostat were compared using the Japanese Adverse Drug Event Report (JADER) database to facilitate their differentiation and promote the management of AEs.
Methods We conducted a descriptive analysis using data from the JADER database from April 2018 to July 2025. The reported AEs for romidepsin and tucidinostat were extracted and classified according to preferred terms (PTs) and system organ classes (SOCs). Reporting odds ratios with 95% confidence intervals were calculated to compare the AE profiles between the groups.
Results In total, 998,397 reports were analysed for all drugs, including 323 for romidepsin and 753 for tucidinostat. Compared with all drugs, both agents showed significant disproportionality signals in four SOCs: Blood and lymphatic system disorders; General disorders and administration site conditions; Investigations; and Neoplasms benign, malignant and unspecified. Romidepsin exhibited additional significant signals in six SOCs: Cardiac disorders, Eye disorders, Gastrointestinal disorders, Immune system disorders, Infections and infestations, and Metabolism and nutrition disorders. Direct comparison between the two agents revealed broader AE profiles for romidepsin, with AEs more frequently reported in eight SOCs, whereas tucidinostat showed AEs in only two SOCs. Romidepsin was associated with AEs more frequently reported in several PTs, including atrial fibrillation and gastrointestinal toxicities, such as constipation, tumour lysis syndrome, hepatotoxicity, and peripheral neuropathy, which was consistent with the results at the SOC level. In contrast, several significant PTs for tucidinostat were observed in General disorders and administration site conditions and Investigations.
Conclusions The Japanese real-world pharmacovigilance analysis showed differences in the AE profiles between romidepsin and tucidinostat. These differences in safety profiles may be useful for treatment selection and AE management in routine clinical practice among patients with R/R PTCL. Further studies are warranted to confirm these findings and better characterise the safety profiles of these agents. en-copyright= kn-copyright= en-aut-name=TakatsuNao en-aut-sei=Takatsu en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoJun en-aut-sei=Matsumoto en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkaYurie en-aut-sei=Oka en-aut-mei=Yurie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakaiTomonori en-aut-sei=Sakai en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwataNaohiro en-aut-sei=Iwata en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigashionnaTsukasa en-aut-sei=Higashionna en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=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= affil-num=1 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Clinical Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Clinical Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Romidepsin kn-keyword=Romidepsin en-keyword=Tucidinostat kn-keyword=Tucidinostat en-keyword=Adverse event kn-keyword=Adverse event en-keyword=JADER kn-keyword=JADER en-keyword=Pharmacovigilance kn-keyword=Pharmacovigilance END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=3 article-no= start-page=e113430 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=Protocol for an open-label, randomised, controlled trial to evaluate the efficacy and safety of sotatercept add-on therapy compared with pulmonary vasodilator-based standard of care for pulmonary vasodilator-resistant pulmonary arterial hypertension associated with unrepaired congenital shunts (atrial septal defect, ventricular septal defect or patent ductus arteriosus), including Eisenmenger syndrome: the SuMILE trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Eisenmenger syndrome and pulmonary arterial hypertension (PAH) due to unrepaired congenital shunts, including atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA), remain life-threatening conditions despite advances in congenital heart disease (CHD) care. In this population, vasodilator-based therapies effective in other forms of PAH have shown limited benefit, and no disease-modifying treatment has been established. Sotatercept, an activin-signalling inhibitor, improved exercise capacity and haemodynamics in phase 2/3 PAH trials; however, patients with unrepaired CHD, including Eisenmenger syndrome, were excluded. The efficacy and safety of sotatercept in this population remain unknown.
Methods and analysis The SuMILE trial is a prospective, exploratory, multicentre, open-label, randomised, controlled trial conducted at 11 Japanese tertiary centres. 36 adults with vasodilator-resistant PAH due to unrepaired ASD, VSD or PDA, including Eisenmenger syndrome, will be randomised 2:1 to sotatercept add-on therapy plus vasodilator-based PAH therapy versus vasodilator-based PAH therapy alone. Sotatercept will be administered subcutaneously every 3 weeks in accordance with label-approved dose-modification rules for haemoglobin and platelet changes. The primary endpoint is the change in 6-min walk distance from baseline to week 24. Key clinical events will be independently adjudicated. Secondary endpoints include all-cause mortality or lung transplantation; pulmonary hypertension-related hospitalisation or initiation of parenteral prostacyclin and changes in WHO functional class, N-terminal pro-brain natriuretic peptide and emPHasis-10. Exploratory endpoints include genotype, right heart catheterisation and cardiac MRI parameters. The primary analysis will use ANCOVA, adjusting for baseline 6-min walk distance and randomisation stratum in the intention-to-treat population.
Ethics and dissemination The protocol has been reviewed and approved by the certified central review board (Kyushu University Hospital Clinical Ethics Review Board) and participating institutions. Written informed consent will be obtained from all participants. Findings will be disseminated through peer-reviewed journals, scientific conferences and trial registries.
Trial registration number Japan Registry of Clinical Trials no. 1071250069; ClinicalTrials.gov NCT07356778. Protocol version and date: V.1.3; 23 October 2025 en-copyright= kn-copyright= en-aut-name=YoshidaKeimei en-aut-sei=Yoshida en-aut-mei=Keimei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HosokawaKazuya en-aut-sei=Hosokawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiraideTakahiro en-aut-sei=Hiraide en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TaniguchiYu en-aut-sei=Taniguchi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AdachiShiro en-aut-sei=Adachi en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InamiTakumi en-aut-sei=Inami en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanishiNaohiko en-aut-sei=Nakanishi en-aut-mei=Naohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KataokaMasaharu en-aut-sei=Kataoka en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SatohTaijyu en-aut-sei=Satoh en-aut-mei=Taijyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TatebeShunsuke en-aut-sei=Tatebe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShinkeToshiro en-aut-sei=Shinke en-aut-mei=Toshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TomitaHideshi en-aut-sei=Tomita en-aut-mei=Hideshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AkazawaYusuke en-aut-sei=Akazawa en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HigakiTakashi en-aut-sei=Higaki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TagawaKoshiro en-aut-sei=Tagawa en-aut-mei=Koshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IshikitaAyako en-aut-sei=Ishikita en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=AsakawaSoshun en-aut-sei=Asakawa en-aut-mei=Soshun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=AbeKohtaro en-aut-sei=Abe en-aut-mei=Kohtaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=3 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Division of Cardiovascular Medicine, Kobe University Hospital kn-affil= affil-num=7 en-affil=Department of Cardiology, Nagoya University Hospital kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Kyorin University School of Medicine kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=10 en-affil=The Second Department of Internal Medicine, University of Occupational and Environmental Health kn-affil= affil-num=11 en-affil=Department of Medical Science and Innovation, SiRIUS Institute of Medical Research, Tohoku University kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Division of Cardiology, Department of Medicine, Showa Medical University Hospital kn-affil= affil-num=14 en-affil=Periatric Heart Disease and Adult Congenital Heart Disease Center, Showa Medical University Hospital kn-affil= affil-num=15 en-affil=Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Pediatric and Adolescent Therapeutic and Developmental Education, Ehime University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Center for Clinical and Translational Research, Kyushu University Hospital kn-affil= affil-num=18 en-affil=Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=19 en-affil=Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=20 en-affil=Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of caffeine on life-history traits on the red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nowadays, addressing insect pest infestation effectively requires environmentally sound and sustainable pest control methods that minimize environmental pollution. Caffeine (1, 3, 7-trimethylxanthine), a plant-derived secondary metabolite, has insecticidal, hormonal and antifeedant properties, making it a promising and more sustainable alternative for pest management. In this study, the red flour beetle Tribolium castaneum Herbst (Coleoptera: Tenebrionidae), a serious stored pest, was used to investigate the effects of different caffeine concentrations on life-history traits. We applied two delivery methods: 1) oral exposure through a caffeine–sucrose solution for adults, and 2) dietary incorporation of caffeine powder mixed with wheat flour and brewer’s yeast for adults and their larvae. To evaluate the effect of caffeine on life-history traits, adult longevity, pupation rate, larval period, pupal weight, adult body size and food consumption were examined. Results revealed higher caffeine concentrations (> 1%) significantly reduced longevity, delayed pupation, decreased pupal number, pupal weight and adult body size in both males and females. Lower caffeine concentration (0.01%) increased pupal number but resulted in lower offspring quality, such as smaller pupal weight and adult size. The results show that caffeine has negative effects on life-history traits of T. castaneum, suggesting its potential use as a natural pesticide in caffeine-based sustainable pest-management programs and integrated pest management (IPM). en-copyright= kn-copyright= en-aut-name=NaingShine Shane en-aut-sei=Naing en-aut-mei=Shine Shane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuuraTeruhisa en-aut-sei=Matsuura en-aut-mei=Teruhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= affil-num=1 en-affil=Okayama University (Graduate School of Environmental, Life, Natural Science and Technology) kn-affil= affil-num=2 en-affil=Okayama University (Graduate School of Environmental, Life, Natural Science and Technology) kn-affil= affil-num=3 en-affil=Okayama University (Graduate School of Environmental, Life, Natural Science and Technology) kn-affil= en-keyword=Insect growth kn-keyword=Insect growth en-keyword=Life-history trait kn-keyword=Life-history trait en-keyword=Longevity kn-keyword=Longevity en-keyword=Pupal weight kn-keyword=Pupal weight en-keyword=Body size kn-keyword=Body size END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=3 article-no= start-page=e70554 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=An Atypical Surgical Case of Lung Cancer With Unilateral Absence of the Pulmonary Artery, With Only the Superior Branch Remaining en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 69-year-old woman was referred to our department for an abnormal shadow on chest radiography. Contrast-enhanced computed tomography (CT) revealed a solid nodule in the right lower lobe and defects in the branches of the middle and lower lobes of the pulmonary artery (PA). Furthermore, collateral circulation had developed via the right internal thoracic, bronchial, intercostal, inferior phrenic, and subdiaphragmatic arteries. The solid nodule was diagnosed as adenocarcinoma by CT-guided biopsy. The day before surgery, embolization was performed using interventional radiology (IVR) to mitigate the risk of bleeding during thoracotomy, resulting in minimal intraoperative bleeding during the subsequent right middle and lower lobectomies with lymph node dissection (ND2a-1). UAPA is a rare congenital abnormality characterized by unilateral pulmonary artery agenesis. The presence of recurrent infections, extensive intrathoracic adhesions, and developed collateral circulation may pose challenges during surgical procedures. en-copyright= kn-copyright= en-aut-name=OkadaKazuhiro en-aut-sei=Okada en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=RyukoTsuyoshi en-aut-sei=Ryuko en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=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 Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=interventional radiology kn-keyword=interventional radiology en-keyword=lung cancer kn-keyword=lung cancer en-keyword=unilateral absence of the pulmonary artery kn-keyword=unilateral absence of the pulmonary 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=20260426 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Counterion condensation, ion pairing and scattering properties of carboxymethyl cellulose with mono- and di-valent ions en-subtitle= kn-subtitle= en-abstract= kn-abstract=We study the scattering and conductometric properties of a semiflexible polyelectrolyte, carboxymethyl cellulose (CMC), with monovalent and divalent counterions in aqueous media without added salts. The scattering patterns for the magnesium salts of CMC display a broad shoulder instead of the scattering peak observed for the monovalent salts. This suggests weaker electrostatic repulsion between chains and a consequent loss of local order. The result is consistent with conductivity measurements, which reveal that the effective charge of the backbone for MgCMC is approximately half that of NaCMC. The decrease in charge density agrees with Oosawa–Manning condensation, which expects the charge density to be inversely proportional to the counterion valence. Alkali metal counterions show large differences in ion-pair formation but only a weak effect in counterion condensation. We suggest that paired ions are a subset of condensed ions. A review of different methods to evaluate counterion condensation, including potentiometry, osmometry and viscosity-based methods is presented. Qualitative agreement between these methods is found and possible reasons for the discrepancies are discussed. en-copyright= kn-copyright= en-aut-name=GharehTapehElmira Abbasi en-aut-sei=GharehTapeh en-aut-mei=Elmira Abbasi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeTakaichi en-aut-sei=Watanabe en-aut-mei=Takaichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HorkayFerenc en-aut-sei=Horkay en-aut-mei=Ferenc kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HouCan en-aut-sei=Hou en-aut-mei=Can kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LopezCarlos G. en-aut-sei=Lopez en-aut-mei=Carlos G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HohenschutzMax en-aut-sei=Hohenschutz en-aut-mei=Max kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Materials Science and Engineering Department, The Pennsylvania State 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=Section on Quantitative Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health kn-affil= affil-num=4 en-affil=Institute of Physical Chemistry, RWTH Aachen University kn-affil= affil-num=5 en-affil=Materials Science and Engineering Department, The Pennsylvania State University kn-affil= affil-num=6 en-affil=Institute of Physical Chemistry, RWTH Aachen University kn-affil= en-keyword=Polyelectrolyte kn-keyword=Polyelectrolyte en-keyword=Counterion condensation kn-keyword=Counterion condensation en-keyword=Carboxymethyl cellulose kn-keyword=Carboxymethyl cellulose en-keyword=SAXS kn-keyword=SAXS en-keyword=Conductivity kn-keyword=Conductivity en-keyword=Ion pairing kn-keyword=Ion pairing END start-ver=1.4 cd-journal=joma no-vol=53 cd-vols= no-issue= article-no= start-page=15 end-page=27 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260331 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=『青と緑』から『波』への実験的手法の考察―色彩と語りの融合― en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=小野和子 kn-aut-sei=小野 kn-aut-mei=和子 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院社会文化科学研究科博士前期課程修了生 END start-ver=1.4 cd-journal=joma no-vol=138 cd-vols= no-issue=1 article-no= start-page=7 end-page=9 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2024 Incentive Award of the Okayama Medical Association in Cancer Research (2024 Hayashibara Prize and Yamada Prize) kn-title=令和６年度岡山医学会賞　がん研究奨励賞（林原賞・山田賞） en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MukoharaFumiaki en-aut-sei=Mukohara en-aut-mei=Fumiaki kn-aut-name=向原史晃 kn-aut-sei=向原 kn-aut-mei=史晃 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, 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　腫瘍微小環境学 END start-ver=1.4 cd-journal=joma no-vol=138 cd-vols= no-issue=1 article-no= start-page=1 end-page=3 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2024 Incentive Award of the Okayama Medical Association in Neuroscience (2024 Niimi Prize) kn-title=令和６年度岡山医学会賞　脳神経研究奨励賞（新見賞） en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HosomotoKakeru en-aut-sei=Hosomoto en-aut-mei=Kakeru kn-aut-name=細本翔 kn-aut-sei=細本 kn-aut-mei=翔 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, 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　脳神経外科学 END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=3 article-no= start-page=e70500 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=Early sedation intensity and psychological outcomes in critically ill adults en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Long-term psychological impairment is a major concern for intensive care unit (ICU) survivors. Early deep sedation during mechanical ventilation has been associated with poor short-term outcomes and mortality after ICU discharge; however, its relationship with psychological outcomes remains unclear.
Aim: To investigate sedation intensity during the first 24 h of mechanical ventilation and its association with psychological impairment 3 months after ICU discharge.
Study Design: This retrospective ancillary analysis of a single-centre cohort study was conducted in two general ICUs at a university hospital in Japan. Eligible patients stayed in the ICU for more than 48 h and received mechanical ventilation for more than 8 h. Sedation intensity was quantified using the Sedation Index (SI) and Agitation Index (AI) derived from Richmond Agitation-Sedation Scale scores during the first 24 h. Psychological impairment 3 months post-ICU discharge was assessed based on symptoms of post-traumatic stress, anxiety and depression. Associations were examined using hierarchical logistic regression.
Results: Among 130 participants, the median age was 64 years, and the median ventilation duration was 14 h. The median SI was 3.0; 47% had SI > 3, and 8.5% had AI > 0. Sedation intensity showed no significant association with psychological impairment (SI: adjusted odds ratio [OR] 0.87, 90% confidence interval [CI] 0.57–1.33, p = 0.59; AI: adjusted OR 0.21, 90% CI 0.01–3.08, p = 0.34). However, any agitation during the ICU stay was associated with psychological outcomes (adjusted OR 2.61, 90% CI 1.16–5.88, p = 0.05).
Conclusions: This study did not identify a statistically significant association between early sedation intensity and psychological impairment 3 months after ICU discharge.
Relevance to Clinical Practice: Critical care nurses should carefully titrate sedation from the initiation of mechanical ventilation to avoid unnecessary deep sedation, considering sedation intensity over time, while actively assessing agitation and its underlying causes. en-copyright= kn-copyright= en-aut-name=IwataniMikiko en-aut-sei=Iwatani en-aut-mei=Mikiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= affil-num=1 en-affil=Okayama University Hospital; Graduate School of Health Sciences, Doctoral Program, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Health Sciences, Okayama University kn-affil= en-keyword=anxiety kn-keyword=anxiety en-keyword=depression kn-keyword=depression en-keyword=post-intensive care syndrome kn-keyword=post-intensive care syndrome en-keyword=post-traumatic stress disorder kn-keyword=post-traumatic stress disorder en-keyword=sedation intensity kn-keyword=sedation intensity END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue=1 article-no= start-page=10 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Compact potential sensor for spacecraft based on a silicon photonic waveguide en-subtitle= kn-subtitle= en-abstract= kn-abstract=Satellites charge up due to incoming electrons and ions, resulting in an electrical potential difference (ΔV) between the satellite and outer space. This can cause electrostatic discharge (ESD) events, damaging electronic devices. To reduce failures due to ESD, sensors monitoring the ΔV can be helpful. Due to spacecraft’s restrictions, the sensors should be as small as possible. While small potential sensors in terrestrial applications are often based on electrical conduction in semiconductors, such sensors are not suitable for space application due to a weak resistance to cosmic radiation and ESD. Here, we report a compact sensor based on another sensing method: the utilization of light absorption in a silicon photonic waveguide. We performed experiments in a vacuum chamber simulating the space plasma environment to demonstrate that the light attenuation in the waveguide depends on the ΔV. Our results further indicate that our sensor exhibits a high resistance to ESD. en-copyright= kn-copyright= en-aut-name=OtsukaKosei en-aut-sei=Otsuka en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahamaWataru en-aut-sei=Takahama en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=HigashiguchiTakeki en-aut-sei=Higashiguchi en-aut-mei=Takeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikunagaKazuya en-aut-sei=Kikunaga en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=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=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Space Systems Engineering, Kyushu Institute of Technology kn-affil= affil-num=4 en-affil=Department of Physics and Electronics, Osaka Metropolitan University kn-affil= affil-num=5 en-affil=Sensing Technology Research Institute, National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=6 en-affil=Electrostatic Engineering DEPT, Kasuga Denki INC kn-affil= affil-num=7 en-affil=Department of Space Systems Engineering, Kyushu Institute of Technology kn-affil= affil-num=8 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=1867 cd-vols= no-issue=3 article-no= start-page=149588 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=Multiple structures of photosystem I-FCPI supercomplexes from a coccolithophore alga reveal a modular antenna organization en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosystem I (PSI) converts light energy into chemical energy in photosynthesis, and forms supercomplexes with light-harvesting complexes (LHCI) in eukaryotes to enhance energy capture and transfer. Various numbers and organizations of both PSI core and LHCI subunits are observed in various organisms. A subgroup of haptophytes named coccolithophores play a major role in marine carbon cycle and CaCO3 production, and the light-harvesting antennas of them are named FCPs (fucoxanthin-chlorophyll a/c binding protein) because they bind chlorophyll c and fucoxanthin in addition to chlorophyll a. A structure of a large PSI-FCPI supercomplex containing 38 FCPI subunits has been reported from a coccolithophore Emiliania huxleyi recently (L. Shen et al., Science 389, eadv2132, 2025). Here we solved five cryo-electron microscopy (cryo-EM) structures of PSI–FCPI supercomplexes isolated from another coccolithophore Chrysotila roscoffensis with different detergents at resolutions ranging from 2.3 to 1.7 Å. These structures represent discrete PSI-FCPIs containing 1, 4, 6, 8 and 9 FCPI subunits, with FCPIs arranged in a modular fashion. Association of each FCPI module to the PSI core, as well as the arrangement of protein subunits and pigments, are revealed. Contributions of individual antenna modules to excitation energy transfer were calculated and compared with PSI–FCPI supercomplexes from other species of coccolithophores and haptophytes. These results pinpoint the assembly of stable PSI–FCPI supercomplexes in C. roscoffensis and provide insights into how antenna modules contribute to energy transfer in coccolithophores. en-copyright= kn-copyright= en-aut-name=La RoccaRomain en-aut-sei=La Rocca en-aut-mei=Romain kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=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=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 ORCID= affil-num=1 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Photosystem I kn-keyword=Photosystem I en-keyword=Light harvesting kn-keyword=Light harvesting en-keyword=Fucoxanthin-chlorophyll a/c binding proteins kn-keyword=Fucoxanthin-chlorophyll a/c binding proteins en-keyword=Haptophytes kn-keyword=Haptophytes en-keyword=Cryo-EM kn-keyword=Cryo-EM END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=2 article-no= start-page=147 end-page=152 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=Complete Transection of the Common Bile Duct Caused by Blunt Abdominal Trauma: A Rare Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Common bile duct (CBD) injury after blunt abdominal trauma is rare and difficult to diagnose. Delayed recognition leads to severe morbidity. A 70-year-old Japanese man was admitted after sustaining blunt abdominal trauma. Ultrasonography revealed intra-abdominal fluid, suggesting bleeding. Contrast-enhanced computed tomography revealed pancreatic head injury, intra-abdominal bleeding, and pseudoaneurysm of the anterior superior pancreatoduodenal artery (ASPDA). Bile duct injury was not evident. The application of transarterial embolization (TAE) controlled the bleeding. Canulation into the pancreatic or biliary duct was not possible during endoscopic retrograde cholangiopancreatography. An emergency laparotomy revealed severe pancreatic head and extrahepatic bile duct injuries. Pancreaticoduodenectomy/Child reconstruction was performed. Complete CBD transection was confirmed. The patient was ultimately discharged without complications. Early recognition, timely surgical management, and intensive care are essential for favorable outcomes in patients who have sustained abdominal trauma. en-copyright= kn-copyright= en-aut-name=SakamotoShinya en-aut-sei=Sakamoto en-aut-mei=Shinya 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=HamadaAkira en-aut-sei=Hamada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshimatsuRika en-aut-sei=Yoshimatsu en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaisakaYuichi en-aut-sei=Saisaka en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoManabu en-aut-sei=Matsumoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwataJun en-aut-sei=Iwata en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkabayashiTakehiro en-aut-sei=Okabayashi en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of 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 Intensive Care Medicine, Kochi Health Sciences Center kn-affil= affil-num=4 en-affil=Department of Radiology, Kochi Health Sciences Center kn-affil= affil-num=5 en-affil=Department of Emergency and Critical Care Medicine, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=7 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= en-keyword=blunt abdominal trauma kn-keyword=blunt abdominal trauma en-keyword=intensive care kn-keyword=intensive care en-keyword=emergency laparotomy kn-keyword=emergency laparotomy en-keyword=pancreatoduodenectomy kn-keyword=pancreatoduodenectomy END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=2 article-no= start-page=141 end-page=145 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=Necrotizing Fasciitis Caused by ESBL-Producing Raoultella ornithinolytica in an Immunocompromised Patient with VEXAS Syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory somatic) syndrome has a poor prognosis, with infections being a major cause of death. Raoultella ornithinolytica is an environmental bacterium found predominantly in soil and water. Although R. ornithinolytica can cause various infections, necrotizing fasciitis due to this bacterium has not been reported. We describe the case of an 84-year-old Japanese male with VEXAS syndrome who developed septic shock and necrotizing fasciitis while he was under immunosuppressive therapy. The pathogen was initially misidentified as R. planticola by mass spectrometry but later confirmed by whole-genome sequencing as extended spectrum β-lactamase (ESBL) produced by R. ornithinolytica. Although a life-saving leg amputation was required, the patient recovered with appropriate antibiotic therapy. R. ornithinolytica is thus able to cause severe skin infections in immunocompromised individuals. en-copyright= kn-copyright= en-aut-name=Sakamoto-TokunagaMoe en-aut-sei=Sakamoto-Tokunaga en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatsuyamaTakayuki en-aut-sei=Katsuyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatobaMasaki en-aut-sei=Matoba en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TamuraTomokazu en-aut-sei=Tamura en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KubotaNatsuki en-aut-sei=Kubota en-aut-mei=Natsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TerajimaYuya en-aut-sei=Terajima en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShidaharaKenta en-aut-sei=Shidahara en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiroseKei en-aut-sei=Hirose en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsumotoKazuya en-aut-sei=Matsumoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NawachiShoichi en-aut-sei=Nawachi en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakadoiTakato en-aut-sei=Nakadoi en-aut-mei=Takato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KatayamaYu en-aut-sei=Katayama en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HayashiKeigo en-aut-sei=Hayashi en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MiyawakiYoshia en-aut-sei=Miyawaki en-aut-mei=Yoshia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KatsuyamaEri en-aut-sei=Katsuyama en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=WatanabeHaruki en-aut-sei=Watanabe en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Takano-NarazakiMariko en-aut-sei=Takano-Narazaki en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 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=19 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=20 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=21 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=22 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=23 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=24 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=21 en-affil=Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=22 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=23 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=24 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=necrotizing fasciitis kn-keyword=necrotizing fasciitis en-keyword=Raoultella ornithinolytica kn-keyword=Raoultella ornithinolytica en-keyword=VEXAS syndrome kn-keyword=VEXAS syndrome en-keyword=whole-genome sequence kn-keyword=whole-genome sequence END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=2 article-no= start-page=131 end-page=139 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=Impact of Proteinuria on Postoperative Complications Following Colorectal Cancer Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Colorectal surgery is associated with a high incidence of postoperative complications regardless of the advances in surgical techniques and multidisciplinary treatment. Proteinuria is common in patients with malignancies, but few studies have investigated the association between preoperative proteinuria and patient prognoses, especially postoperative complications. We investigated the impact of proteinuria on patients undergoing colorectal surgery in a single-center, retrospective cohort study of 767 patients who underwent surgical resection for colorectal cancer between January 2016 and December 2022 at the National Hospital Organization Shikoku Cancer Center. Among them, 81 patients with preoperative proteinuria were compared with the control group of 686 patients without proteinuria. Our analyses revealed that the patients with proteinuria had malnutrition with a significantly lower prognostic nutritional index compared to the no-proteinuria control group (p<0.001). The proteinuria group had a significantly advanced tumor stage (p=0.005), experienced more bleeding during the surgery (p=0.002), and required more transfusions (p<0.001). Postoperative complications were significantly more frequent in the proteinuria group (p=0.03), thus demonstrating that proteinuria was independently associated with postoperative complications (p=0.045). Proteinuria in patients undergoing colorectal cancer surgery can therefore be considered a risk factor for postoperative complications. en-copyright= kn-copyright= en-aut-name=NakataShunsuke en-aut-sei=Nakata en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakatsuFumiaki en-aut-sei=Takatsu en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MikuriyaYoshihiro en-aut-sei=Mikuriya en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KakishitaTomokazu en-aut-sei=Kakishita en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HatoShinji en-aut-sei=Hato en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhtaKoji en-aut-sei=Ohta en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobatakeTakaya en-aut-sei=Kobatake en-aut-mei=Takaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=surgery kn-keyword=surgery en-keyword=proteinuria kn-keyword=proteinuria en-keyword=complication kn-keyword=complication en-keyword=malnutrition kn-keyword=malnutrition END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=2 article-no= start-page=119 end-page=129 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=Mini-open Corpectomy and Posterior Spinal Fixation with Single-Position Surgery in Lateral Decubitus Position for Osteoporotic Thoracolumbar Vertebral Collapse in Elderly Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=We evaluated the clinical outcomes and limitations of anterior and posterior combined surgery with a mini-open corpectomy applying an expandable cage (Xcore®) and percutaneous pedicle screw (PPS) fixation using single-position surgery in the lateral decubitus position in patients aged > 75 years with thoracolumbar vertebral collapse. The cases of 30 consecutive patients who underwent this procedure and had ≥ 1-year follow-up were retrospectively analyzed. The mean operative time was 78.8 min and the estimated blood loss was 115.7 ml per level. The complications included adjacent junctional failure (n=9, 30%), deep venous thrombosis (n=3, 10%), delirium (n=3, 10%), pleural injury (n=2, 6%), screw backout (n=1, 3%) kidney injury (n=1, 3%), chylothorax (n=1, 3%), and wound dehiscence (n=1, 3%). Seven cases (23.3%) required reoperation. Local kyphosis showed significant improvement (p<0.05) that was maintained at the final follow-up. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire and a visual analogue scale indicated significant improvement in all categories at the final follow-up (p<0.05). The use of mini-open corpectomy and posterior fixation with SPAPS can thus provide reliable radiological correction and good postoperative clinical outcomes even in patients aged > 75 years. However, a limitation of this procedure is the rate of reoperation (23.3%) for osteoporosis-related adjacent segment fracture and screw backout. en-copyright= kn-copyright= en-aut-name=IkumaHisanori en-aut-sei=Ikuma en-aut-mei=Hisanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiroseTomohiko en-aut-sei=Hirose en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawasakiKeisuke en-aut-sei=Kawasaki en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtsukaKazutoshi en-aut-sei=Otsuka en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=4 en-affil=Otsuka Orthopedic Clinic kn-affil= en-keyword=single postion surgery kn-keyword=single postion surgery en-keyword=osteoporotic vertebral collapse kn-keyword=osteoporotic vertebral collapse en-keyword=anterior and posterior combined surgery kn-keyword=anterior and posterior combined surgery en-keyword=minimum invasive surgery kn-keyword=minimum invasive surgery END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=2 article-no= start-page=99 end-page=107 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=Consistent Clinical Outcomes of Anteroinferior Minimally Invasive Plate Osteosynthesis for Midshaft Clavicle Fractures Across AO/OTA Fracture Types en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although the performance of minimally invasive plate osteosynthesis (MIPO) via the anteroinferior approach is increasingly adopted for midshaft clavicle fractures, the influence of fracture morphology on clinical outcomes under a standardized protocol is unclear. We retrospectively analyzed the cases of 54 patients who underwent anteroinferior MIPO for an acute midshaft clavicle fracture (AO/OTA types B1, B2, B3) performed by a single surgeon across three affiliated institutions (2009-2022). We evaluated the clinical outcomes, i.e., the surgical time, incision length, radiographic union, reduction accuracy, range of motion, pain (visual analog scale [VAS]), and complications and compared them among the three AO/OTA subtypes. The mean incision length (3.4 cm) and surgical time (71-79 min) were similar among the groups (both p>0.2). All fractures achieved radiographic union at a mean of 3.5 months. Postoperative alignment and clavicular length were maintained (length reduction −1.0±2.2 mm [B1], −0.5±2.0 mm [B2], −0.6±1.8 mm [B3]; p=0.825; angulation −0.8±3.4°, −1.1±3.1°, −0.3±3.3°; p=0.888). At 3 months, shoulder elevation and abduction were 169°-175° (p=0.079) and 164°-175° (p=0.324). Pain was minimal (100-mm VAS: ≤1 mm; p=0.782). One plate-fatigue failure occurred; no supraclavicular-nerve symptoms were recorded. Anteroinferior MIPO yielded consistent outcomes across AO/OTA types, with excellent union rates, functional recovery, and few complications, indicating that this technique is safe and reproducible for the surgical management of midshaft clavicle fractures. en-copyright= kn-copyright= en-aut-name=Nguyen Trung Thanh en-aut-sei=Nguyen Trung Thanh en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamichiRyo en-aut-sei=Nakamichi en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShimamuraYasunori en-aut-sei=Shimamura en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitoTaichi en-aut-sei=Saito en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FurutaniTomoki en-aut-sei=Furutani en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShitozawaHisakazu en-aut-sei=Shitozawa en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NodaTomoyuki en-aut-sei=Noda en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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, Kousei Hospital kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Kawasaki Medical School General Medical Center kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=clavicle fracture kn-keyword=clavicle fracture en-keyword=minimally invasive plate osteosynthesis kn-keyword=minimally invasive plate osteosynthesis en-keyword=anteroinferior plating kn-keyword=anteroinferior plating en-keyword=AO/OTA classification kn-keyword=AO/OTA classification END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=2 article-no= start-page=75 end-page=83 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=Involvement of ADAM12 in TGF-β1-Induced Proliferation of Rheumatoid Arthritis Synovial Fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=A disintegrin and metalloproteinase 12 (ADAM12) is known to be involved in chondrocyte proliferation and is upregulated in the synovial tissue of osteoarthritis (OA). However, the underlying mechanisms of ADAM12 on rheumatoid arthritis (RA) synovial cell proliferation remain unknown. Here, we investigated the role of ADAM12 in the proliferation of RA synovial fibroblasts (RASFs). The expression and localization of ADAM12 in RA synovial tissues were examined by immunohistochemistry and compared with OA and healthy control (HC) synovial tissues. The effect of inflammatory cytokines (TNF-α, TGF-β1, and PDGF-BB) on ADAM12 expression in RASFs from RA patients was examined by real-time RT-PCR. The effect of ADAM12 knock-down by ADAM12 siRNA and ADAM12 overexpression on cell proliferation of RASFs were examined by WST-1 assay. ADAM12 was identified predominantly in RA synovial tissue rather than OA and HC synovial tissues. Stimulation with TGF-β1 upregulated the expression of ADAM12 and cell proliferation of RASFs. ADAM12 siRNA suppressed TGF-β1-induced cell proliferation of RASFs, while ADAM12 overexpression promoted the cell proliferation of RASFs. These findings demonstrate that ADAM12 may have a key role in TGF-β1-induced cell proliferation of synovial fibroblasts in patients with RA. en-copyright= kn-copyright= en-aut-name=LinDeting en-aut-sei=Lin en-aut-mei=Deting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HoritaMasahiro en-aut-sei=Horita en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeMasahito en-aut-sei=Watanabe en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtsukaNoriaki en-aut-sei=Otsuka en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IchikawaChinatsu en-aut-sei=Ichikawa en-aut-mei=Chinatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuNoriyuki en-aut-sei=Shimizu en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NaniwaShuichi en-aut-sei=Naniwa en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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, Faculty of Medical Development Field, Okayama University kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Muscat Orthopaedic Clinic kn-affil= affil-num=4 en-affil=Medical Information and Assistive Technology Development, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Division of Chronic Pain Medicine and Division of Comprehensive Rheumatology, Locomotive Pain Center, Faculty of Medical Development Field, Okayama University kn-affil= en-keyword=rheumatoid arthritis kn-keyword=rheumatoid arthritis en-keyword=synovial tissue kn-keyword=synovial tissue en-keyword=TGF-β1 kn-keyword=TGF-β1 en-keyword=ADAM12 kn-keyword=ADAM12 en-keyword=cell proliferation kn-keyword=cell proliferation END start-ver=1.4 cd-journal=joma no-vol=367 cd-vols= no-issue= article-no= start-page=199714 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=Virome of the fungi associated with mushroom dry bubble disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dry bubble disease, attributed to the filamentous fungus Lecanicillium fungicola (Cordycipitaceae) results in huge yield losses in mushroom (Agaricus bisporus) cultivation worldwide. The possibilities for controlling the disease using commercial fungicides are highly limited, and therefore, there is an increasing demand for novel, alternative means of pest management. Our research objective was the comprehensive examination of viruses in the causal agents of dry bubble disease, which may open up an avenue for its virocontrol in the future. Out of 57 fungal isolates obtained from dry bubble-affected A. bisporus crops in various countries, 47 (82%) were confirmed by ITS (Internal Transcribed Spacer) sequence analysis as L. fungicola. In addition, different members of the genera Akanthomyces and Simplicillium (7 and 3 isolates, respectively), yet unknown to cause dry bubble symptoms, have also been detected. Cellulose column chromatography revealed the presence of double-stranded (ds) RNA in seven L. fungicola and three Akanthomyces sp. isolates, suggesting viral infection. The ten dsRNA-positive and eight randomly selected dsRNA-negative fungal strains were subjected to rRNA-depletion high-throughput RNA-sequencing analysis. The presence of seven new viruses representing four new species in the established families, Partitiviridae, Polymycoviridae, Botourmiaviridae and the narna-like virus group, and three previously established/proposed species in the families Chrysoviridae and “Mycovirgaviridae” were confirmed. The impact of the detected and identified viruses on their host fungi, and their potential applicability for virocontrol purposes will be examined in the future. This study provides the first detailed report on viruses of mushroom pathogenic fungi. en-copyright= kn-copyright= en-aut-name=HatvaniLóránt en-aut-sei=Hatvani en-aut-mei=Lóránt kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisanoSakae en-aut-sei=Hisano en-aut-mei=Sakae 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=SugaharaHitomi en-aut-sei=Sugahara en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TelengechPaul en-aut-sei=Telengech en-aut-mei=Paul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShahiSabitree en-aut-sei=Shahi en-aut-mei=Sabitree kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IbiangSarah Remi en-aut-sei=Ibiang en-aut-mei=Sarah Remi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KocsubéSándor en-aut-sei=Kocsubé en-aut-mei=Sándor kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KartaliTünde en-aut-sei=Kartali en-aut-mei=Tünde kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FitzpatrickDavid A. en-aut-sei=Fitzpatrick en-aut-mei=David A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=GroganHelen en-aut-sei=Grogan en-aut-mei=Helen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant 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=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=8 en-affil=Department of Biotechnology and Microbiology, Faculty of Science and Informatics, University of Szeged kn-affil= affil-num=9 en-affil=Department of Biotechnology and Microbiology, Faculty of Science and Informatics, University of Szeged kn-affil= affil-num=10 en-affil=Genome Evolution Laboratory, Department of Biology, Maynooth University kn-affil= affil-num=11 en-affil=Teagasc Food Research Center, Horticulture Development Department kn-affil= affil-num=12 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Lecanicillium fungicola kn-keyword=Lecanicillium fungicola en-keyword=Agaricus bisporus kn-keyword=Agaricus bisporus en-keyword=Akanthomyces kn-keyword=Akanthomyces en-keyword=Simplicillium kn-keyword=Simplicillium en-keyword=dsRNA kn-keyword=dsRNA en-keyword=Myovirus kn-keyword=Myovirus en-keyword=Fungal virus kn-keyword=Fungal virus en-keyword=Mycovirgaviridae kn-keyword=Mycovirgaviridae en-keyword=Partitiviridae kn-keyword=Partitiviridae en-keyword=Polymycoviridae kn-keyword=Polymycoviridae en-keyword=Botourmiaviridae kn-keyword=Botourmiaviridae en-keyword=Splipalmiviridae kn-keyword=Splipalmiviridae en-keyword=Narna-like virus kn-keyword=Narna-like virus END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=3 article-no= start-page=101428 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=Short- and long-term outcomes of anti-thymocyte globulin-based regimen for acute antibody-mediated rejection after lung transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Antibody-mediated rejection (AMR) remains a major barrier to successful lung transplantation (LTx). Despite advances in donor-specific alloantibody (DSA) detection, effective treatments are limited, with current management largely empirical. Acute clinical AMR, marked by rapid graft dysfunction, demands urgent intervention. In Japan, where approved therapies for AMR were historically limited, rabbit anti-thymocyte globulin (rATG) has been adopted as a treatment option.
Methods: This retrospective study analyzed 11 patients who developed acute AMR within three months after LTx at Okayama University Hospital between 2013 and 2023. Diagnosis (ISHLT possible AMR) was based on acute graft dysfunction unresponsive to steroids, positive DSA, and exclusion of infection, without histological confirmation due to procedural risk. rATG (1.5 mg/kg/day for 7 days) was administered, along with intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and rituximab when indicated. Outcomes included DSA clearance, clinical response, survival, and adverse events.
Results: Remission was achieved in 64% of patients, with 36% not requiring PLEX and 64% not receiving rituximab. Early rATG treatment correlated with favorable outcomes, whereas delayed therapy resulted in poorer responses. Six patients (55%) survived without chronic lung allograft dysfunction (CLAD) for over one year. Adverse events included cytomegalovirus infection (91%), bacterial pneumonia (36%), fungal infection (18%), and malignancy (18%).
Conclusions: rATG was effective for acute possible AMR management, particularly when initiated early. Some patients achieved remission without adjunct therapy, indicating rATG's potent immunosuppressive activity. However, frequent infectious complications emphasize the need for optimized dosing and further studies to validate its safety and long-term efficacy. en-copyright= kn-copyright= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaniShinji en-aut-sei=Otani en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=5 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=6 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=Anti-thymocyte globulin kn-keyword=Anti-thymocyte globulin en-keyword=Acute antibody-mediated rejection kn-keyword=Acute antibody-mediated rejection en-keyword=Treatment kn-keyword=Treatment en-keyword=Lung transplantation kn-keyword=Lung transplantation END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260409 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rice EMF3 Alleles Adjust Flower Opening Time to Enhance the Seed Setting Rate Under High Temperature Stress en-subtitle= kn-subtitle= en-abstract= kn-abstract=To safeguard global food security against rapid population growth and a warming world, the effective genetic improvement of cereals is imperative. Flower opening time (FOT) critically affects the seed setting rate. In this study, we identified a gene, EARLY-MORNING FLOWERING 3 (EMF3), in which single-nucleotide substitutions strongly modulate FOT in rice in a semi-dominant manner, resulting in wide variation in FOT from earlier to later FOT than the wild-type. EMF3 knock-out mutants showed significantly reduced FOT synchrony and disrupted anther dehiscence, leading to fertilisation failure. EMF3 encodes a plasma membrane-localised polypeptide of 723 amino acids with an armadillo repeat fold and four transmembrane segments. Furthermore, EMF3 is specifically expressed in the anthers starting from nighttime on the day of flowering, with substantial impacts on the transcriptomes of both anther and lodicule, which suggested an exclusive role of EMF3 in flowering events. Modifying EMF3 alleles of O. sativa enabled the adjustment of FOT among Oryza species and subspecies, potentially facilitating cross-fertilisation by overcoming one of the major challenges of inter-specific hybridisation to exploit heterosis. Introducing the EMF3 alleles with the earlier FOT into popular rice cultivars resulted in flowering at an earlier time of day when the temperature was cooler, efficiently increasing seed setting rate under heat stress. This discovery unveils the novel mechanism of anther control of flower opening time through the EMF3 gene, while also enabling the use of EMF3 alleles in breeding strategies for efficient fertilisation for increasing hybrid rice seed production and mitigating future heat-stress damage at flowering. en-copyright= kn-copyright= en-aut-name=IshizakiTakuma en-aut-sei=Ishizaki en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HashidaYoichi en-aut-sei=Hashida en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirabayashiHideyuki en-aut-sei=Hirabayashi en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasakiKazuhiro en-aut-sei=Sasaki en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TokunagaHiroki en-aut-sei=Tokunaga en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Simon‐AdaEliza Vie M. en-aut-sei=Simon‐Ada en-aut-mei=Eliza Vie M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WakayamaMasataka en-aut-sei=Wakayama en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakaiToshiyuki en-aut-sei=Takai en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SaitoHiroki en-aut-sei=Saito en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaganoAtsushi J. en-aut-sei=Nagano en-aut-mei=Atsushi J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakakibaraHitoshi en-aut-sei=Sakakibara en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KojimaMikiko en-aut-sei=Kojima en-aut-mei=Mikiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakebayashiYumiko en-aut-sei=Takebayashi en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KimSung‐Ryul en-aut-sei=Kim en-aut-mei=Sung‐Ryul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MatsushimaRyo en-aut-sei=Matsushima en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ThomsonMichael J. en-aut-sei=Thomson en-aut-mei=Michael J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SugimotoKazuhiko en-aut-sei=Sugimoto en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HibaraKen‐Ichiro en-aut-sei=Hibara en-aut-mei=Ken‐Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshimaruTsutomu en-aut-sei=Ishimaru en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Tropical Agriculture Research Front, Japan International Research Center for Agricultural Sciences (JIRCAS) kn-affil= affil-num=2 en-affil=Faculty of Agriculture, Takasaki University of Health and Welfare kn-affil= affil-num=3 en-affil=Institute of Crop Science, National Agriculture and Food Research Organization (NARO) kn-affil= affil-num=4 en-affil=Biological Resources and Post-Harvest Division, Japan International Research Center for Agricultural Sciences (JIRCAS) kn-affil= affil-num=5 en-affil=Tropical Agriculture Research Front, Japan International Research Center for Agricultural Sciences (JIRCAS) kn-affil= affil-num=6 en-affil=Plant Breeding, Genetics, and Biotechnology Division, International Rice Research Institute (IRRI) kn-affil= affil-num=7 en-affil=Institute for Advanced Biosciences, Keio University kn-affil= affil-num=8 en-affil=Plant Breeding, Genetics, and Biotechnology Division, International Rice Research Institute (IRRI) kn-affil= affil-num=9 en-affil=Tropical Agriculture Research Front, Japan International Research Center for Agricultural Sciences (JIRCAS) kn-affil= affil-num=10 en-affil=Institute for Advanced Biosciences, Keio University kn-affil= affil-num=11 en-affil=Graduate School of Bioagricultural Sciences, Nagoya University kn-affil= affil-num=12 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=13 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=14 en-affil=Rice Breeding Innovations Department, International Rice Research Institute (IRRI) kn-affil= affil-num=15 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=16 en-affil=Plant Breeding, Genetics, and Biotechnology Division International Rice Research Institute (IRRI) Metro Manila Philippines kn-affil= affil-num=17 en-affil=Institute of Crop Science, National Agriculture and Food Research Organization (NARO) kn-affil= affil-num=18 en-affil=18Graduate School of Agricultural Regional Vitalization, Kibi International University kn-affil= affil-num=19 en-affil=Biological Resources and Post-Harvest Division, Japan International Research Center for Agricultural Sciences (JIRCAS) kn-affil= en-keyword=EARLY-MORNING FLOWERING 3 kn-keyword=EARLY-MORNING FLOWERING 3 en-keyword=flower opening time kn-keyword=flower opening time en-keyword=heat stress kn-keyword=heat stress en-keyword=rice kn-keyword=rice en-keyword=seed setting rate kn-keyword=seed setting rate END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=11550 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260302 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pseudohypoxia induced by iron chelators preserves working memory performance in aged mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pseudohypoxia refers to a physiological condition wherein hypoxia-inducible factor (HIF) is pharmacologically upregulated under normoxia, thereby modulating immune responses. We hypothesized that pseudohypoxia, induced by iron chelators, may similarly potentiate systemic immune responses in aged mice, concurrently triggering neuro-regenerative signaling pathways and enhancing cognitive performance. In this study, aged mice (43–48 weeks old) were orally administered two iron chelators, Super Polyphenol 10 (SP10) or Roxadustat, to induce a pseudohypoxia. An 8-week oral regimen of SP10 and Roxadustat significantly preserved working memory, as assessed by the Y-maze test (YMT). White blood cell counts and hippocampal volume, as assessed by magnetic resonance imaging (MRI), were elevated in the treatment groups relative to controls. Pseudohypoxia induced by SP10 tended to enhance neuro-regenerative signaling, specifically involving the Tau and JNK pathways, and potentially modulated Doublecortin (DCX) expression, although statistical significance was limited by sample size. Importantly, inflammatory markers, such as ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP), were not elevated by treatment. Collectively, these findings suggest that pseudohypoxia induced by iron chelators preserves working memory performance accompanied by leukocytosis, without concomitant neuroinflammation. en-copyright= kn-copyright= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwasakiYoshiaki en-aut-sei=Iwasaki en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KasaiTomonari en-aut-sei=Kasai en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KomakiShiho en-aut-sei=Komaki en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HamadaYusuke en-aut-sei=Hamada en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Health Service Section, Environment Health & Safety Intelligence Department, Okayama University kn-affil= affil-num=3 en-affil=Department of Applied Energy, Graduate School of Engineering, Nagoya University kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Hypoxia-inducible factor kn-keyword=Hypoxia-inducible factor en-keyword=Working memory kn-keyword=Working memory en-keyword=Hippocampus kn-keyword=Hippocampus en-keyword=Iron kn-keyword=Iron END start-ver=1.4 cd-journal=joma no-vol=220 cd-vols= no-issue=3 article-no= start-page=29 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Knot surgered elliptic surfaces without 1- and 3-handles for a (2, 2h + 1)-torus knot en-subtitle= kn-subtitle= en-abstract= kn-abstract=For any positive integers h and n, we show that a knot surgered elliptic surface E(n)T(2,2h+1) for a (2, 2h + 1)-torus knot T (2, 2h + 1) admits a handle decomposition without 1- and 3-handles using a Kirby diagram derived from a Lefschetz fibration on it. As a corollary, an elliptic surface E(1)2,2h+1 has such a handle decomposition. en-copyright= kn-copyright= en-aut-name=MondenNaoyuki en-aut-sei=Monden en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YabuguchiReo en-aut-sei=Yabuguchi en-aut-mei=Reo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Mathematics, Faculty of Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Mathematics, Faculty of Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Triangulation in teaching probability: teaching materials for the theoretical foundations of probability in real-world applications en-subtitle= kn-subtitle= en-abstract= kn-abstract=This paper proposes using the concept of triangulation with probabilistic models as a means to enhance theoretical inversion for deepening students’ understanding of the nature of probability in real-world contexts. Triangulation refers to the combined application of multiple methodologies to investigate the same phenomenon, particularly in the social sciences. Theoretical inversion refers to a shift in focus from surprising outcomes to the theoretical foundations of probability. The paper introduces three types of problem-solving tasks designed to enhance one of four types of triangulations: theory triangulation. Theoretical inversion is expected to emerge through engaging in these tasks. The characteristics of the problems are as follows. Problem 1 promotes students to compare different probabilistic models of events under similar procedures. Problem 2 provides students with an opportunity to simplify an experiment by omitting steps that add no new information. Problem 3 enhances students’ ability to recognise how subtle differences in the experimental setup can affect the resulting probability. These tasks are designed to encourage students to view probabilistic reasoning as a form of modelling and to appreciate the importance of assumptions, definitions of elementary events, and clarity in procedural descriptions. en-copyright= kn-copyright= en-aut-name=UegataniYusuke en-aut-sei=Uegatani en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshibashiIppo en-aut-sei=Ishibashi en-aut-mei=Ippo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakotaAya en-aut-sei=Sakota en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Hiroshima University High School kn-affil= affil-num=2 en-affil=Faculty of Education, Okayama University kn-affil= affil-num=3 en-affil=Hiroshima University High School kn-affil= en-keyword=Probability kn-keyword=Probability en-keyword=triangulation kn-keyword=triangulation en-keyword=mathematical modelling kn-keyword=mathematical modelling en-keyword=theoretical inversion kn-keyword=theoretical inversion END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=5 article-no= start-page=2308 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Aerobic Exercise Attenuates Epidermal Hyperplasia in an Obesity-Associated Psoriasiform Dermatitis Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Obesity is an important risk factor for psoriasis, and clinical studies indicate that exercise interventions can improve disease severity. However, the mechanisms by which exercise influences psoriatic pathogenesis remain insufficiently understood. To investigate the effects of aerobic exercise on obesity-associated psoriasis, wild-type mice were fed a high-fat diet (HFD) for 7 weeks to induce obesity and subsequently underwent moderate-intensity treadmill running for 3 weeks. Psoriasiform dermatitis was induced by daily topical application of imiquimod (IMQ) to the skin for five consecutive days. HFD increased body weight, epididymal fat mass, and serum cholesterol. HFD-fed mice developed more severe IMQ-induced psoriatic skin changes compared with normal diet-fed mice. Treadmill exercise modestly reduced body weight gain and attenuated epidermal hyperplasia in HFD-fed mice. In contrast, inflammatory cytokine expression, including Tnfa, Il17a, and Il23a, showed modest increases in the skin of HFD-fed exercised mice, which did not parallel the improvement in epidermal hyperplasia. Overall, these findings indicate that while obesity exacerbates psoriasiform dermatitis, aerobic exercise ameliorates epidermal hyperplasia in obese mice without corresponding changes in inflammatory cytokine expression in the skin, suggesting that exercise may influence psoriatic skin changes through multiple metabolic and immunological pathways. en-copyright= kn-copyright= en-aut-name=MatsudaYoshihiro en-aut-sei=Matsuda en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakezakiDaiki en-aut-sei=Takezaki en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoYuma en-aut-sei=Sakamoto en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BabaNobuyasu en-aut-sei=Baba en-aut-mei=Nobuyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IsekiMasanori en-aut-sei=Iseki en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawakamiYoshio en-aut-sei=Kawakami en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShiomiTatsushi en-aut-sei=Shiomi en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MukaiTomoyuki en-aut-sei=Mukai en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology, Kawasaki Medical School kn-affil= affil-num=9 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= en-keyword=psoriasis kn-keyword=psoriasis en-keyword=obesity kn-keyword=obesity en-keyword=aerobic exercise kn-keyword=aerobic exercise en-keyword=imiquimod kn-keyword=imiquimod en-keyword=high-fat diet kn-keyword=high-fat diet END start-ver=1.4 cd-journal=joma no-vol=49 cd-vols= no-issue=2 article-no= start-page=364 end-page=370 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260221 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Functional Transport Properties of Human Zinc Transporter 1: Kinetics and pH-Dependency en-subtitle= kn-subtitle= en-abstract= kn-abstract=Intracellular zinc (Zn2+) homeostasis is essential for physiological and pathological processes and is strictly regulated by Zn2+ transporters. Zinc transporter 1 (ZnT1) is a ubiquitously expressed plasma membrane-localized Zn transporter that exports Zn2+ from the cytoplasm to the extracellular space. However, the functional transport properties regarding kinetics and driving forces of ZnT1 remain debatable. In this study, we established a cell-free proteoliposome assay system and demonstrated that ZnT1 transports Zn2+ with high affinity in pH-dependent and pH-independent manners. The Km and Vmax of pH-dependent Zn2+ transport were 0.40 μM and 15.13 nmol/min/mg protein, and those of pH-independent Zn2+ transport were 0.52 μM and 8.88 nmol/min/mg protein (low concentrations of Zn2+), 3.02 μM and 17.59 nmol/min/mg protein (high concentrations of Zn2+), respectively, suggesting biphasic kinetic components of Zn2+ transport. Even without pH gradient formation, ZnT1 exhibits potent Zn2+ transport activity. In pH dependency, Zn2+ transport activity was higher at an inside pH of 6.0 than at 6.5–7.5 for proteoliposomes, despite the same ΔpH of 0.5–1.5. The Zn2+ transport activity decreased at an outside pH of 8.0, despite an increase in ΔpH. Although previous studies have proposed that ZnT1-mediated Zn2+ transport activity is driven by a calcium (Ca2+) gradient and not by a pH gradient, Ca2+ does not enhance Zn2+ transport activity in the presence or absence of a pH gradient. These results strongly suggest that ZnT1 protein transports Zn2+ optimally at a specific pH and exports excess intracellular Zn2+ even without ΔpH. en-copyright= kn-copyright= en-aut-name=YoshiokaYuma en-aut-sei=Yoshioka en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyajiTakaaki en-aut-sei=Miyaji en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Molecular Membrane Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Molecular Membrane Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=zinc transporter 1 kn-keyword=zinc transporter 1 en-keyword=SLC30A1 kn-keyword=SLC30A1 en-keyword=zinc kn-keyword=zinc en-keyword=pH kn-keyword=pH en-keyword=proteoliposome kn-keyword=proteoliposome END