start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=5 article-no= start-page=e70124 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Direct and Element‐Mediated Edaphic Effects Shape Resource‐Conservative Leaf Trait Variation Across Serpentine and Limestone Soils en-subtitle= kn-subtitle= en-abstract= kn-abstract=Edaphically extreme substrates, such as serpentine and limestone, impose strong physiological constraints on plants and are frequently associated with resource-conservative leaf traits and narrow plant endemism. However, it remains unclear how edaphic selection shapes leaf traits and whether these shifts are driven primarily by direct soil-imposed constraints or indirectly by changes in leaf elemental composition. Here, we examined soil?leaf elemental relationships, leaf functional traits, and CSR strategies (Competitive, Stress-tolerant, and Ruderal strategy) using piecewise structural equation modeling across 16 populations of five closely related Epimedium taxa distributed on serpentine, limestone, and other substrates in western Japan. Despite marked differences in soil and leaf elemental composition between serpentine and limestone sites, populations on both substrates converged toward resource-conservative leaf traits, including lower specific leaf area (SLA) and a shift toward thicker leaves and higher leaf dry matter content (LDMC), even after accounting for species identity. Piecewise structural equation modeling revealed two pathways consistent with the proposed hypotheses: A strong direct association between soil elemental composition and leaf trait variation and a weaker indirect association involving leaf elemental composition. Together, our results suggest that edaphic mosaics are linked to convergent resource-conservative phenotypes through two partly overlapping pathways across serpentine and limestone soils: strong direct associations with leaf functional traits and weaker associations involving leaf elemental composition. en-copyright= kn-copyright= en-aut-name=UeyamaShogo en-aut-sei=Ueyama en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KusatakeEmi en-aut-sei=Kusatake en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MimuraMakiko en-aut-sei=Mimura en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Biology, Okayama University kn-affil= affil-num=2 en-affil=Department of Biology, Okayama University kn-affil= affil-num=3 en-affil=Department of Biology, Okayama University kn-affil= en-keyword=CSR scheme kn-keyword=CSR scheme en-keyword=edaphic stress kn-keyword=edaphic stress en-keyword=leaf economics spectrum kn-keyword=leaf economics spectrum en-keyword=stress tolerance kn-keyword=stress tolerance en-keyword=trait convergence kn-keyword=trait convergence END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=76 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sequence and timing of organ donation discussions in brain-dead donors: a subanalysis of the J-RESPECT study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The optimal timing of organ donation discussions in patients with catastrophic brain injury remains unclear. In Japan, national guidance recommends providing information after recognition of a state compatible with brain death; however, real-world practice has not been well characterized. This study aimed to evaluate the sequence of organ donation option presentation relative to clinical determination of a brain death-compatible state and to assess option presentation timing.
Methods We conducted a multicenter retrospective cohort study using data from the J-RESPECT study, including adult brain-dead donors from 16 institutions in Japan between 2010 and 2023. Donors were classified as brain death-first (option presented after clinical determination of a brain death-compatible state) or option-first (option presented before such determination). Mixed-effects logistic and linear regression models with random intercepts for institution were used to examine factors associated with presentation sequence and timing.
Results Among 190 donors, 76 (40%) were classified as brain death-first and 114 (60%) as option-first. In mixed-effects logistic regression, age was the only independent factor associated with presentation sequence (adjusted OR 1.03 per year, 95% CI 1.00?1.07), while substantial between-institution variability was observed (intraclass correlation coefficient?=?0.32). Institutional timing policy was not significantly associated with presentation sequence. The median interval from admission to option presentation was 5 days in the brain death-first group and 2 days in the option-first group (p? Conclusions Substantial inter-institutional variability exists in the sequence and timing of organ donation discussions in Japan. Further studies are needed to determine optimal approaches to organ donation communication and timing in clinical practice. en-copyright= kn-copyright= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HayakawaMineji en-aut-sei=Hayakawa en-aut-mei=Mineji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YokoboriShoji en-aut-sei=Yokobori en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiyamaKei en-aut-sei=Nishiyama en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AtsumiTakahiro en-aut-sei=Atsumi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TasakiOsamu en-aut-sei=Tasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsurukiriJunya en-aut-sei=Tsurukiri en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HayamizuMariko en-aut-sei=Hayamizu en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MurahashiShimon en-aut-sei=Murahashi en-aut-mei=Shimon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayashiMunehiro en-aut-sei=Hayashi en-aut-mei=Munehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NishimuraTakeshi en-aut-sei=Nishimura en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=GotoYukari en-aut-sei=Goto en-aut-mei=Yukari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NarumiyaHiromichi en-aut-sei=Narumiya en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MizutaniAtsushi en-aut-sei=Mizutani en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MiyajimaMamoru en-aut-sei=Miyajima en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ShimazakiJunya en-aut-sei=Shimazaki en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MiuraTakeshi en-aut-sei=Miura en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShimaNozomu en-aut-sei=Shima en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=DeuchiKazuki en-aut-sei=Deuchi en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NakayasuHitomi en-aut-sei=Nakayasu en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KanoHitoshi en-aut-sei=Kano en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=J-RESPECT study group en-aut-sei=J-RESPECT study group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Emergency Medicine, Hokkaido University Hospital kn-affil= affil-num=4 en-affil=Department of Emergency Medicine, Hokkaido University Hospital kn-affil= affil-num=5 en-affil=Division of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental Science kn-affil= affil-num=6 en-affil=Department of Emergency and Disaster Medicine, Hamamatsu University School of Medicine kn-affil= affil-num=7 en-affil=Acute and Critical Care Center, Nagasaki University Hospital kn-affil= affil-num=8 en-affil=Emergency and Critical Care Medicine, Tokyo Medical University Hachioji Medical Center kn-affil= affil-num=9 en-affil=Department of Emergency Medicine, Hokkaido University Hospital kn-affil= affil-num=10 en-affil=Acute and Critical Care Center, Nagasaki University Hospital kn-affil= affil-num=11 en-affil=Department of Emergency and Critical Care Medicine, Japanese Red Cross Medical Center kn-affil= affil-num=12 en-affil=Department of Emergency and Critical Care Medicine, Hyogo Emergency Medical Center kn-affil= affil-num=13 en-affil=Department of Emergency Medicine, Nagoya Ekisaikai Hospital kn-affil= affil-num=14 en-affil=Department of Emergency and Critical Care Medicine, Japanese Red Cross Kyoto Daini Hospital kn-affil= affil-num=15 en-affil=Department of Emergency Medicine, Hamamatsu Medical Center kn-affil= affil-num=16 en-affil=Emergency and Critical Care Center, Nagaoka Red Cross Hospital kn-affil= affil-num=17 en-affil=Department of Emergency and Critical Care Medicine, Kansai Medical University Medical Center kn-affil= affil-num=18 en-affil=Department of Emergency and Critical Care Medicine, Institute of Medicine, University of Tsukuba Hospital kn-affil= affil-num=19 en-affil=Department of Emergency and Critical Care Medicine, Wakayama Medical University kn-affil= affil-num=20 en-affil=Division of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental Science kn-affil= affil-num=21 en-affil=Emergency and Critical Care Medicine, Seirei Hamamatsu General Hospital kn-affil= affil-num=22 en-affil=Department of Emergency Medicine, Hokkaido University Hospital kn-affil= affil-num=23 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=24 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=25 en-affil= kn-affil= en-keyword=Brain death kn-keyword=Brain death en-keyword=Communication kn-keyword=Communication en-keyword=Decision-making kn-keyword=Decision-making en-keyword=End-of-life care kn-keyword=End-of-life care en-keyword=Intensive care kn-keyword=Intensive care en-keyword=Organ donation kn-keyword=Organ donation END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=20 article-no= start-page=3418 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20261020 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association Between Urine pH and Kidney Outcomes in Patients with Biopsy-Proven Kidney Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Lower urine pH has been associated with reduced kidney function and increased risk of kidney disease, but its prognostic and pathological significance in biopsy-proven kidney disease remains unclear. Medullary cast formation has been shown to predict adverse renal outcomes beyond cortical interstitial fibrosis and tubular atrophy (IFTA), although its clinical determinants are not fully understood. We examined the associations of urine pH with kidney outcomes and medullary cast formation in patients undergoing native kidney biopsy. Methods: Among 1167 adults who underwent native kidney biopsy between 2011 and 2024, 503 patients with evaluable medullary tissue were included. Urine pH was analyzed in relation to clinical and histological variables and kidney outcomes. The primary outcome was a ?40% decline in estimated glomerular filtration rate (eGFR) or initiation of renal replacement therapy. Results: Mean baseline eGFR was 60.7 ± 26.2 mL/min/1.73 m2 and urine pH was 6.15 ± 0.84. During a median follow-up of 2.11 years, 113 patients (22.5%) reached the outcome. Lower urine pH was associated with higher risk of kidney outcomes. In multivariable Cox models, urine pH remained independently associated with outcomes (hazard ratio per 1-unit increase, 0.69; 95% CI, 0.52?0.92). Addition of urine pH modestly improved discrimination (C-index 0.642 to 0.654; likelihood ratio test, p = 0.009). Lower urine pH was associated with greater medullary cast formation in unadjusted analysis. Conclusions: Lower urine pH was independently associated with adverse kidney outcomes and with greater medullary cast formation, suggesting that urine pH may reflect intratubular pathological changes associated with CKD progression. en-copyright= kn-copyright= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueYoshitaka en-aut-sei=Inoue en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=urine pH kn-keyword=urine pH en-keyword=kidney outcomes kn-keyword=kidney outcomes en-keyword=medullary casts kn-keyword=medullary casts en-keyword=global glomerulosclerosis kn-keyword=global glomerulosclerosis en-keyword=interstitial fibrosis and tubular atrophy kn-keyword=interstitial fibrosis and tubular atrophy END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=10 article-no= start-page=e70664 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=Oncological Outcomes and Safety Profiles of Adjuvant Nivolumab in Muscle‐Invasive Urothelial Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives
Perioperative immunotherapy has become the standard of care in patients with high-risk muscle-invasive urothelial carcinoma (MIUC). This study aimed to clarify oncological outcomes and safety profiles of adjuvant nivolumab therapy in MIUC, focusing on upper tract urothelial carcinoma (UTUC).
Methods
This multicenter study comprised 97 patients undergoing removal of primary tumors, followed by adjuvant nivolumab therapy with a potential follow-up period ??12?months. Patients were divided according to the primary tumor location: bladder cancer (BC), n?=?66 (68%); UTUC, n?=?31 (32%). Multivariable Cox regression analyses were applied to identify prognostic factors for disease-free survival (DFS).
Results
Before surgery, 38% of patients had an estimated glomerular filtration rate (eGFR)? Conclusions
Adjuvant nivolumab therapy may provide comparable oncological outcomes between BC and UTUC. Baseline eosinophil count was an independent prognosticator for DFS. The incidences of adrenal insufficiency and hypophysitis appeared higher in our real-world data. Clinicians should recognize these irAEs due to nonspecific symptoms and considerable variability in time of onset. en-copyright= kn-copyright= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 ORCID= en-aut-name=InoueShota en-aut-sei=Inoue en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WatanabeTomofumi en-aut-sei=Watanabe en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=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=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsuboiKazuma en-aut-sei=Tsuboi en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MuraoWataru en-aut-sei=Murao en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakadaTetsuya en-aut-sei=Nakada en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OgawaKohei en-aut-sei=Ogawa en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 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=17 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 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=20 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=Departmentof Urology, The Jikei University School of Medicine kn-affil= affil-num=4 en-affil=Departmentof Urology, The Jikei University School of Medicine 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, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=12 en-affil=Department of Urology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=13 en-affil=Department of Urology, Shimane University Hospital kn-affil= affil-num=14 en-affil=Departmentof Urology, The Jikei University School of Medicine kn-affil= affil-num=15 en-affil=Departmentof Urology, The Jikei University School of Medicine kn-affil= affil-num=16 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Urology, Shimane University Hospital kn-affil= affil-num=19 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=20 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=adjuvant nivolumab kn-keyword=adjuvant nivolumab en-keyword=eosinophil kn-keyword=eosinophil en-keyword=hypophysitis kn-keyword=hypophysitis en-keyword= upper tract urothelial carcinoma kn-keyword= upper tract urothelial carcinoma en-keyword=urothelial carcinoma kn-keyword=urothelial carcinoma END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=8 article-no= start-page=1658 end-page=1667 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260611 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Differential impact of host-related factors on survival outcomes between IO+IO and IO+TKI in metastatic renal cell carcinoma: a multicenter retrospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Immune checkpoint inhibitor (ICI)-based combination therapies, including immune checkpoint inhibitor plus immune checkpoint inhibitor (IO?+?IO) and immune checkpoint inhibitor plus tyrosine kinase inhibitor (IO?+?TKI) regimens, have significantly improved outcomes in metastatic renal cell carcinoma (mRCC). However, the prognostic impact of host-related factors in patients receiving these therapies remains unclear.
Methods We retrospectively analyzed 493 patients with mRCC treated with IO+IO (n?=?205) or IO+TKI (n?=?288) as first-line therapy. Survival outcomes and treatment responses were evaluated according to host-related factors using Cox proportional hazards models.
Results In the IO+IO cohort, multiple host-related factors were independently associated with worse overall survival, including BMI? Conclusion The prognostic impact of host-related factors differs according to treatment regimen in mRCC. These findings suggest that host immune and metabolic conditions play a more prominent role in immune-driven IO+IO therapy, whereas tumor-related factors may predominate in IO+TKI therapy. en-copyright= kn-copyright= en-aut-name=SugimotoKoichi en-aut-sei=Sugimoto en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ToyodaShingo en-aut-sei=Toyoda en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InokiLan en-aut-sei=Inoki en-aut-mei=Lan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TamuraKeita en-aut-sei=Tamura en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NukayaTakuhisa en-aut-sei=Nukaya en-aut-mei=Takuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaenosonoRyoichi en-aut-sei=Maenosono en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorinakaHirofumi en-aut-sei=Morinaka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=KomuraKazumasa en-aut-sei=Komura en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakaharaKiyoshi en-aut-sei=Takahara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=InamotoTeruo en-aut-sei=Inamoto en-aut-mei=Teruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AzumaHaruhito en-aut-sei=Azuma en-aut-mei=Haruhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujitaKazutoshi en-aut-sei=Fujita en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=4 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=6 en-affil=Department of Urology, Hamamatsu University School of Medicine kn-affil= affil-num=7 en-affil=Department of Urology, Fujita Health University School of Medicine kn-affil= affil-num=8 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=9 en-affil=Department of Urology, Kawasaki Medical School 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, Kawasaki Medical School kn-affil= affil-num=13 en-affil=Department of Urology, Fujita Health University School of Medicine kn-affil= affil-num=14 en-affil=Department of Urology, Hamamatsu University School of Medicine kn-affil= affil-num=15 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=16 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= en-keyword=Metastatic renal cell carcinoma kn-keyword=Metastatic renal cell carcinoma en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors en-keyword=Host-related factors kn-keyword=Host-related factors en-keyword=Prognosis kn-keyword=Prognosis en-keyword=Combination therapy kn-keyword=Combination therapy END start-ver=1.4 cd-journal=joma no-vol=61 cd-vols= no-issue=3 article-no= start-page=895 end-page=902 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A Comparative Analysis of the CID Pilot Program, Special Rate-Based BIDs, and Voluntary Membership?Based BIDs - A case study of New South Wales, Australia - kn-title=CIDパイロットプロジェクトとSpecial Rate型BIDおよび寄付金型BIDの比較分析 -オーストラリア・ニューサウスウェールズ州を対象として- en-subtitle= kn-subtitle= en-abstract=Japanese Area Management Levy System stagnates due to high consensus hurdles. This study investigates the multilayered BID framework in New South Wales, Australia, to derive implications for Japan. Research findings reveal that system selection depends on city scale: government-led "Special Rate" models are predominant in regional areas, while private-sector-led "CID Projects" or "Membership-type BIDs" are favored in urban centers. Based on these insights, this paper proposes a phased transition model for Japan that facilitates a shift from administration-led structures to private-authority systems as local organizational capacity matures. Enabling flexible, scale-appropriate choices is essential for lowering implementation barriers and revitalizing area management activities in Japanese cities. kn-abstract=日本のエリアマネジメント負担金制度は、合意形成に要する高い同意要件が原因で停滞している。本研究は、オーストラリア・ニューサウスウェールズ州における三類型のBID（Business　Improvement District）を調査し、日本のエリアマネジメント活動の改善に資する提案を行うことを目的とする。調査の結果、制度は都市規模に応じて活用されていることが明らかとなった。地方都市では行政が主な権限を要する「Special Rate型BID」が展開されている一方、都市部では民間側が主な権限を要する「CIDパイロットプロジェクト」や「寄付金型BID」が展開されている。これらの知見に基づき、本論文は、地域の組織能力の成熟度に合わせて行政主導から民間主体へと体制を移行させる「段階的移行モデル」を提案する。柔軟かつ都市規模に適した制度選択を可能にすることは、導入障壁を下げ、日本の都市におけるエリアマネジメント活動を活性化させる上で不可欠である。 en-copyright= kn-copyright= en-aut-name=HoriHirofumi en-aut-sei=Hori en-aut-mei=Hirofumi kn-aut-name=堀裕典 kn-aut-sei=堀 kn-aut-mei=裕典 aut-affil-num=1 ORCID= en-aut-name=KitanoTatsuya en-aut-sei=Kitano en-aut-mei=Tatsuya kn-aut-name=北野達也 kn-aut-sei=北野 kn-aut-mei=達也 aut-affil-num=2 ORCID= affil-num=1 en-affil=Okayama University kn-affil=岡山大学学術研究院環境生命自然科学学域 affil-num=2 en-affil=Okayama University kn-affil=岡山大学大学院環境生命自然科学研究科 en-keyword=BID kn-keyword=BID en-keyword=エリアマネジメント (Area Based Management) kn-keyword=エリアマネジメント (Area Based Management) en-keyword=地域再生エリアマネジメント負担金制度 (Japanese BID System) kn-keyword=地域再生エリアマネジメント負担金制度 (Japanese BID System) en-keyword=地方都市 (Regional Cities) kn-keyword=地方都市 (Regional Cities) en-keyword=Special Rate kn-keyword=Special Rate END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=5 article-no= start-page=317 end-page=325 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Radiogenomic Analysis of Contrast-Enhanced MRI for Predicting Pathogenic BRCA Variants in Ovarian Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study evaluated the feasibility of predicting pathogenic BRCA1/2 variants in ovarian cancer using radiogenomic analysis of contrast-enhanced MRI. Twenty six patients were analyzed, including 14 with pathogenic BRCA1/2 variants and 12 without. Contrast enhanced MRI was used to generate two dimensional (2D) and three dimensional (3D) tumor segmentations. Radiomic features extracted with PyRadiomics were reduced using least absolute shrinkage and selection operator (LASSO) regression, yielding two selected features. Linear discriminant analysis (LDA) models were trained on 18 patients and tested on 8, with performance assessed using sensitivity, specificity, accuracy, and the area under the receiver operating characteristic (ROC) curve. The DeLong test compared AUCs between segmentation methods. Automated machine learning (AutoML) was performed with a training set of 20 patients and a test set of 6, with multiple performance metrics calculated. LDA achieved approximately 60% accuracy in both 2D and 3D test datasets. AUCs were 0.80 (3D) and 0.77 (2D), with no significant difference (p=0.85). AutoML identified CatBoost_BAG_L2_FULL as the optimal model, achieving accuracy above 80%. MRI-based radiogenomic analysis demonstrated moderate classification performance for identifying pathogenic BRCA1/2 variants in ovarian cancer. These preliminary findings suggest a potential role for noninvasive prediction, warranting further validation in larger cohorts. en-copyright= kn-copyright= en-aut-name=SaitoHayato en-aut-sei=Saito en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukuiRyohei en-aut-sei=Fukui en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugiharaHanako en-aut-sei=Sugihara en-aut-mei=Hanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TadaAkihiro en-aut-sei=Tada en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Okayama University kn-affil= affil-num=4 en-affil=Okayama Diagnostic Imaging Center kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= en-keyword=ovarian cancer kn-keyword=ovarian cancer en-keyword=BRCA1/2 kn-keyword=BRCA1/2 en-keyword=radiogenomics kn-keyword=radiogenomics en-keyword=machine learning kn-keyword=machine learning en-keyword=MRI kn-keyword=MRI END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=5 article-no= start-page=309 end-page=316 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dynamics of Serum Amyloid A Levels in the Blood, Brain and Liver in a Mouse Model of Focal Cerebral Ischemia en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study examined the dynamics of serum amyloid A (SAA) levels in the blood, brain, and liver over time using a mouse model of focal cerebral ischemia induced by occlusion of the middle cerebral artery (MCA) for 4 h followed by reperfusion. Blood SAA concentrations increased transiently after cerebral infarction, coinciding with changes in brain and liver SAA gene expression and protein levels. SAA concentrations in the brain, liver, and blood increased at similar time points after cerebral infarction, suggesting that SAA may serve as an important indicator of the associated pathological condition. en-copyright= kn-copyright= en-aut-name=EgashiraSaki en-aut-sei=Egashira en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakanoTakafumi en-aut-sei=Nakano en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IrieKeiichi en-aut-sei=Irie en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UshioSoichiro en-aut-sei=Ushio en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ManabeAkiko en-aut-sei=Manabe en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MasakiAyuko en-aut-sei=Masaki en-aut-mei=Ayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MukaiRie en-aut-sei=Mukai en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraYoshihiko en-aut-sei=Nakamura en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HosokawaMasato en-aut-sei=Hosokawa en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SathoTomomitsu en-aut-sei=Satho en-aut-mei=Tomomitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SanoKazunori en-aut-sei=Sano en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MishimaKenichi en-aut-sei=Mishima en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=2 en-affil=Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=3 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=4 en-affil=Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=5 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=6 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=7 en-affil=Department of Microbiology Laboratory, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=8 en-affil=Department of Emergency and Critical Care Medicine, Fukuoka University Hospital kn-affil= affil-num=9 en-affil=Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=10 en-affil=Department of Microbiology Laboratory, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=11 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=12 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= en-keyword=stroke kn-keyword=stroke en-keyword=cerebral ischemia kn-keyword=cerebral ischemia en-keyword=serum amyloid A kn-keyword=serum amyloid A en-keyword=temporal dynamics kn-keyword=temporal dynamics END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=5 article-no= start-page=289 end-page=298 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High Accuracy of Pelvic Tilt Measurement Using Three-Dimensional Planning Software: A Validation Study Using Dry Bone Models en-subtitle= kn-subtitle= en-abstract= kn-abstract=The “CR Alignment” function was recently introduced in ZedHip?, the hip joint module of ZedView?, to evaluate pelvic tilt in non-supine positions via two-dimensional (2D)?3D matching using radiographs. However, its ccuracy has not been validated. This study therefore evaluated the accuracy of pelvic tilt measurements using the CR Alignment function in dry pelvic bone specimens. Two cadaveric pelvic bone models were placed in nine orientations (anterior/posterior tilt and left/right rotation). Both radiographic and CT images were acquired in each position. In Study 1, pelvic tilt measured directly from CT images was defined as the “true value.” Three observers used the CR Alignment function to calculate pelvic tilt on radiographs, and measurement errors were determined relative to the true values. In Study 2, measurement errors were compared between matched (same position) and mismatched (different position) imaging. In Study 1, the mean measurement error was 1.28±0.64°. Intra- and interobserver intraclass correlation coefficients were 0.996-0.998 and 0.997, respectively. In Study 2, the mean errors were 1.20±0.88° (matched) and 1.32±1.03° (mismatched). This software exhibited high accuracy and reproducibility in 2D?3D matching of pelvic tilt, with lower variability under matched acquisition, demonstrating its utility for pre- and postoperative assessment in joint arthroplasty. en-copyright= kn-copyright= en-aut-name=KomutaYuki en-aut-sei=Komuta en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ImaiNorio en-aut-sei=Imai en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HommaDaisuke en-aut-sei=Homma en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FunayamaKazuhisa en-aut-sei=Funayama en-aut-mei=Kazuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HiranoYuki en-aut-sei=Hirano en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HorigomeYoji en-aut-sei=Horigome en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MinatoIzumi en-aut-sei=Minato en-aut-mei=Izumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawashimaHiroyuki en-aut-sei=Kawashima en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=2 en-affil=Division of Comprehensive Musculoskeletal Medicine, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=3 en-affil=Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=4 en-affil=Division of Legal Medicine, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=5 en-affil=Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=6 en-affil=Division of Comprehensive Musculoskeletal Medicine, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Niigata Rinko Hospital kn-affil= affil-num=8 en-affil=Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= en-keyword=total hip arthroplasty kn-keyword=total hip arthroplasty en-keyword=pelvic tilt kn-keyword=pelvic tilt en-keyword=three-dimensional planning software kn-keyword=three-dimensional planning software en-keyword=two-dimensional and threedimensional matching kn-keyword=two-dimensional and threedimensional matching en-keyword=radiographic analysis kn-keyword=radiographic analysis END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=5 article-no= start-page=271 end-page=277 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Artificial Intelligence-Assisted Peroral Cholangioscopy for the Diagnosis and Management of Biliary Strictures: Current Evidence and Future Directions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Peroral cholangioscopy (POCS) enables direct intraductal visualization and targeted biopsies for indeterminate biliary strictures. However, its diagnostic performance remains operator-dependent and is limited by sampling error. As artificial intelligence (AI) has rapidly advanced in gastrointestinal endoscopy, AI-assisted cholangioscopy has progressed from proof-of-concept image classification to multicenter validation, feature detection, and real-time application. Recent studies using digital single-operator cholangioscopy have reported diagnostic accuracy comparable to that of experts in differentiating malignant from benign strictures, and feature-based approaches can automatically detect tumor vessels and other key visual characteristics. Beyond classification, generative models may enhance mucosal and margin visualization through virtual chromoendoscopy, potentially improving lesion-margin assessment. Furthermore, new models compatible with multiple systems are emerging to address device heterogeneity, which is a key barrier to routine practice. This review summarizes the current evidence on AI-assisted POCS, discusses practical considerations for clinical translation, and highlights future directions, including real-time integration and multimodal decision support. en-copyright= kn-copyright= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=peroral cholangioscopy kn-keyword=peroral cholangioscopy en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=biliary stricture kn-keyword=biliary stricture en-keyword=deep learning kn-keyword=deep learning en-keyword=virtual chromoendoscopy kn-keyword=virtual chromoendoscopy END start-ver=1.4 cd-journal=joma no-vol=51 cd-vols= no-issue=10 article-no= start-page=533 end-page=547 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Integration of QSAR modeling and in vitro validation for identification of food-derived Nrf2 activators against arsenic-induced toxicity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Arsenic exposure is a major public health concern due to its toxicity and carcinogenicity, largely mediated by oxidative stress, and activation of the Nrf2 signaling pathway is considered a promising strategy to mitigate such damage. In this study, a quantitative structure?activity relationship (QSAR) model was developed to identify potential Nrf2 activators from food-derived compounds. Machine learning algorithms, including Random Forest (RF), Support Vector Machine (SVM), Linear Discriminant Analysis (LDA), and a stacking model, were developed and optimized. The optimized RF, SVM, and LDA models were subsequently integrated into a stacking framework, which was selected as the final predictive model for virtual screening based on its robust and balanced predictive performance. The stacking model achieved the highest accuracy during five-fold cross-validation (0.77) and demonstrated competitive performance on the independent test set (0.742 ± 0.040), with balanced precision, sensitivity, and F-measure. Consequently, the stacking model was selected as the final model for virtual screening. A total of 70,926 compounds retrieved from a food-derived database were filtered based on physicochemical criteria, and QSAR-based virtual screening predicted 920 compounds as potential activators of the Nrf2 signaling pathway, from which 5,7-Dimethylchrysin (FooDB ID: FDB015537) and Demethylvestitol (FooDB ID: FDB012218) were selected for experimental validation. In vitro assays using HepG2 cells demonstrated that 5,7-Dimethylchrysin significantly enhanced cell viability against sodium arsenite (150 μM)-induced cytotoxicity, with an effective concentration (EC50) of 0.54 μM, whereas Demethylvestitol exhibited only limited protective effects. Furthermore, luciferase reporter assays confirmed that 5,7-Dimethylchrysin activated antioxidant response element (ARE)-driven transcription in a concentration-dependent manner, producing a 1.5 to 2.4-fold increase at concentrations ranging from 0.78 to 6.25 μM. Overall, these findings highlight the effectiveness of integrating QSAR modeling with experimental validation to identify food-derived compounds with protective potential against arsenic-induced toxicity, with 5,7-Dimethylchrysin emerging as a promising candidate for further investigation. en-copyright= kn-copyright= en-aut-name=HuongNgo Thanh en-aut-sei=Huong en-aut-mei=Ngo Thanh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KodamaSusumu en-aut-sei=Kodama en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnoAtsushi en-aut-sei=Ono en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Laboratory of Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Laboratory of Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Laboratory of Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Arsenic toxicity kn-keyword=Arsenic toxicity en-keyword=Nrf2 activator kn-keyword=Nrf2 activator en-keyword=QSAR modeling kn-keyword=QSAR modeling en-keyword=Food-derived compounds kn-keyword=Food-derived compounds en-keyword=In vitro kn-keyword=In vitro END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=10 article-no= start-page=1697 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20261010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Purification, Structural Characterization, and Genomic Insights of an Anti-MRSA Peptide from Mangrove-Derived Brevibacillus sp. A34 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The widespread prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in community and healthcare settings has driven the urgent search for novel antibacterial agents. Mangrove sediments are an underexplored source of antimicrobial-producing bacteria. This study characterized an antimicrobial fraction and the genome of the mangrove-derived isolate Brevibacillus sp. A34. The active fraction was purified via ammonium sulfate precipitation, cation-exchange chromatography, and reversed-phase chromatography. De novo MS/MS analysis assigned the octapeptide LLLLLLAH (905.19 Da), designated as A34 AMP, which was further confirmed by chemical synthesis. This active peptide inhibited all four tested S. aureus strains, including three MRSA strains, with a minimum inhibitory concentration (MIC) of 62 ?g/mL. At 2× and 4× MIC, A34 AMP exhibited a concentration-dependent bactericidal effect within 20 h. Increased SYTOX Green uptake and morphological alterations supported a membrane permeabilization mechanism, and antimicrobial activity was retained following thermal, pH, protease, and surfactant treatments. Genome mining identified 23 putative biosynthetic gene clusters, including an 11-module nonribosomal peptide synthetase (NRPS) cluster linked to A34 AMP through three-dimensional adenylation-domain modeling. Collectively, these findings highlight A34 AMP from Brevibacillus sp. A34 as a promising bioactive anti-staphylococcal peptide scaffold. en-copyright= kn-copyright= en-aut-name=ThonginThanyamai en-aut-sei=Thongin en-aut-mei=Thanyamai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SermkaewNamfa en-aut-sei=Sermkaew en-aut-mei=Namfa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AtipairinApichart en-aut-sei=Atipairin en-aut-mei=Apichart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KrobthongSucheewin en-aut-sei=Krobthong en-aut-mei=Sucheewin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AonbangkhenChanat en-aut-sei=Aonbangkhen en-aut-mei=Chanat kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SongnakaNuttapon en-aut-sei=Songnaka en-aut-mei=Nuttapon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=School of Pharmacy, Walailak University kn-affil= affil-num=2 en-affil=School of Pharmacy, Walailak University kn-affil= affil-num=3 en-affil=School of Pharmacy, Walailak University kn-affil= affil-num=4 en-affil=Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University kn-affil= affil-num=5 en-affil=Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University kn-affil= affil-num=6 en-affil=Department of Infectious Diseases, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan kn-affil= affil-num=7 en-affil=School of Pharmacy, Walailak University kn-affil= en-keyword=Brevibacillus sp. kn-keyword=Brevibacillus sp. en-keyword=antimicrobial peptide kn-keyword=antimicrobial peptide en-keyword=AMP kn-keyword=AMP en-keyword=mangrove kn-keyword=mangrove en-keyword=genome kn-keyword=genome en-keyword=anti-MRSA kn-keyword=anti-MRSA END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=20 article-no= start-page=3393 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20261012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cross-Cultural Adaptation and Initial Psychometric Evaluation of the Japanese Version of the Chronic Kidney Disease Self-Efficacy Scale (CKDSE-J) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Self-efficacy is an important determinant of self-care among adults with chronic kidney disease (CKD). The Chronic Kidney Disease Self-Efficacy Scale (CKD-SE) is a disease-specific measure, but its use has not been reported in Japan. This study translated and culturally adapted the CKD-SE into Japanese and conducted an initial psychometric evaluation. Methods: A cross-sectional survey was conducted among Japanese adults with CKD stages G3a?G5 not receiving dialysis. Structural validity and internal consistency were evaluated in 227 participants, and construct validity was evaluated in 222. Structural validity was examined using confirmatory factor analysis (CFA) and exploratory structural equation modeling (ESEM). Results: The original 25-item four-factor CFA showed a poor fit, and ESEM yielded an improper solution involving Item 19. Sequential evaluation resulted in a 23-item structure. The 23-item CFA showed mixed fit, whereas Target ESEM showed improved overall fit (CFI = 0.935, TLI = 0.902, RMSEA = 0.060, SRMR = 0.033). However, several autonomy items showed weak target loadings and cross-loadings. Proposed subscale scores correlated positively with self-care behavior (r = 0.27?0.46), and McDonald’s omega ranged from 0.84 to 0.90. Conclusions: The 23-item CKDSE-J showed improved overall model fit under Target ESEM, but the structural definition of autonomy remained uncertain. Because the structure was refined and evaluated in the same sample, independent replication and further psychometric evaluation are needed. en-copyright= kn-copyright= en-aut-name=GengTingting en-aut-sei=Geng en-aut-mei=Tingting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KajiwaraYuki en-aut-sei=Kajiwara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimotoMichiko en-aut-sei=Morimoto en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Doctor’s Program, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Health Sciences, Okayama University kn-affil= en-keyword=chronic kidney disease kn-keyword=chronic kidney disease en-keyword=self-efficacy kn-keyword=self-efficacy en-keyword=self-care kn-keyword=self-care en-keyword=cultural adaptation kn-keyword=cultural adaptation en-keyword=psychometric evaluation kn-keyword=psychometric evaluation en-keyword=exploratory structural equation modeling kn-keyword=exploratory structural equation modeling END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=11689307 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tourism Demand Forecasting Using Machine Learning with Cross-Model Feature Ranking en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study proposes a machine learning (ML) framework for forecasting tourist visits to a destination, leveraging feature ranking consistency across heterogeneous models. The proposed framework uses a unified stepwise feature selection pipeline to systematically determine a subset of given features that reduces prediction error of an ML model. The transferability of feature rankings is demonstrated through experiments using ML models including Random Forest, XGBoost, LightGBM, and Support Vector Regression (SVR), and a dataset related to tourist visits to West Sumatra, Indonesia. Experimental results show that i) SVR using top four features in the feature ranking based on SHAP achieves the highest accuracy and ii) application of the feature ranking based on XGBoost improves performance stability across other models, reducing error fluctuations. These findings reveal that an optimized feature subset combined with cross-model ranking transfer can outperform more complex ensembles, highlighting the importance of ranking robustness in tourism forecasting. The proposed framework provides a methodological foundation for building interpretable and dataefficient decision support systems for tourism management and policy planning. en-copyright= kn-copyright= en-aut-name=HendraYomei en-aut-sei=Hendra en-aut-mei=Yomei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MigitaTsuyoshi en-aut-sei=Migita en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiNorikazu en-aut-sei=Takahashi en-aut-mei=Norikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Okayama University kn-affil= affil-num=3 en-affil=Okayama University kn-affil= en-keyword=tourism forecasting kn-keyword=tourism forecasting en-keyword=machine learning kn-keyword=machine learning en-keyword=support vector regression kn-keyword=support vector regression en-keyword=XGBoost kn-keyword=XGBoost en-keyword=feature ranking kn-keyword=feature ranking END start-ver=1.4 cd-journal=joma no-vol=248 cd-vols= no-issue= article-no= start-page=117443 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202611 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Molecular characteristics and clinical outcomes of ERBB2-activating mutation-positive non-small cell lung cancer: A Japanese nationwide real-world cohort en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Erb-b2 receptor tyrosine kinase 2 (ERBB2)-activating mutations are well-documented oncogenic drivers in non-small cell lung cancer (NSCLC), occurring in approximately 1?4% of cases. These alterations include a heterogeneous spectrum of variant subtypes; however, the clinicogenomic characteristics and clinical significance of the individual variants have yet to be elucidated.
Methods: We searched the nationwide Center for Cancer Genomics and Advanced Therapeutics database, which integrates comprehensive genome profiling data generated in routine clinical practice across Japan, to investigate the molecular landscape and clinical outcomes of patients with ERBB2-mutated NSCLC.
Results: A total of 319 patients with ERBB2-activating mutations were included in this retrospective analysis. Although 74% of the patients harbored canonical tyrosine kinase domain (TKD) in-frame insertions, 26% carried noncanonical variants, including TKD missense (8%), transmembrane/juxtamembrane domain (10%), and extracellular domain (ECD) mutations (8%). Co-occurring oncogenic driver alterations were identified in only 18 cases (5.6%) and were largely restricted to noncanonical variants, whereas no co-occurring driver alterations were detected among patients with TKD in-frame mutations. Noncanonical variants?TKD missense and ECD mutations in particular?were associated with an increased tumor mutational burden. Among 288 patients with available survival data, 78 (27%) received trastuzumab deruxtecan (T-DXd) during their clinical course. After excluding patients who had started treatment with T-DXd before undergoing comprehensive genome profiling testing, time-dependent T-DXd exposure was associated with a reduced risk of death (adjusted hazard ratio, 0.63; 95% confidence interval, 0.39?1.01; P?=?0.057).
Conclusions: ERBB2-mutated NSCLC exhibited substantial molecular heterogeneity, with canonical TKD in-frame insertions characterized by a low frequency of co-occurring oncogenic driver alterations. Among patients harboring ERBB2-activating mutations, exposure to T-DXd was associated with improved overall survival. en-copyright= kn-copyright= en-aut-name=YamashitaMasahiro en-aut-sei=Yamashita en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoritaAyako en-aut-sei=Morita en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaraNaofumi en-aut-sei=Hara en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakadaKenji en-aut-sei=Takada en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= en-keyword=ERBB2 mutation kn-keyword=ERBB2 mutation en-keyword=Variant subtype kn-keyword=Variant subtype en-keyword=Comprehensive genomic profiling kn-keyword=Comprehensive genomic profiling en-keyword=Trastuzumab-deruxtecan kn-keyword=Trastuzumab-deruxtecan en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer END start-ver=1.4 cd-journal=joma no-vol=218 cd-vols= no-issue= article-no= start-page=109516 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ULK1, a novel therapeutic target to delay drug tolerance to EGFR?TKIs in an EGFR-mutant non-small cell lung cancer model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The presence of drug-tolerant persister (DTP) cells reduces the effectiveness of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in EGFR-mutated non-small cell lung cancer (NSCLC). Although autophagy is a potential target for eliminating DTP cells, clinical trials targeting autophagy in EGFR-mutant NSCLC have been unsuccessful?likely because most trials have utilized chloroquine, non-specifically inhibiting autophagy targeting lysosomes with dose limitations. This study focused on unc-51-like autophagy activating kinase 1 (ULK1), a more specific target for autophagy inhibition, to assess whether ULK1 inhibition delays the emergence of tolerance to EGFR-tyrosine kinase inhibitors in EGFR-mutant NSCLC cells.
Methods: DTP cells were generated by treating EGFR-mutant NSCLC cell lines with osimertinib. Autophagy status and ULK1 expression were evaluated using immunofluorescence, western blotting, and quantitative real-time PCR. The effects of both pharmacological and genetic inhibition of ULK1 were examined in vitro and in vivo.
Results: ULK1 and LC3-II, markers of autophagy, were upregulated in DTP cells. Inhibition of ULK1, either pharmacologically or genetically, suppressed autophagy, prevented the formation of DTP cells, and enhanced the antitumor activity of osimertinib in both in vitro and in vivo models. Furthermore, upregulation of ULK1 expression through serum starvation conferred tolerance to osimertinib, reinforcing ULK1′s role in drug tolerance. Notably, ULK1 inhibition showed modest efficacy even after cells transitioned to the DTP or acquired resistance states.
Conclusion: ULK1 plays a critical role in mediating drug tolerance in EGFR-mutant NSCLC. Targeting ULK1 represents a promising therapeutic approach to enhance the efficacy of EGFR-TKIs and to delay the development of drug tolerance. en-copyright= kn-copyright= en-aut-name=MoritaAyako en-aut-sei=Morita en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiTatsuya en-aut-sei=Nishi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaraNaofumi en-aut-sei=Hara en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OchiNobuaki en-aut-sei=Ochi en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of General Internal Medicine 4, Kawasaki Medical School kn-affil= affil-num=13 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= en-keyword=ULK1 kn-keyword=ULK1 en-keyword=Autophagy kn-keyword=Autophagy en-keyword=EGFR kn-keyword=EGFR en-keyword=TKI kn-keyword=TKI en-keyword=Osimertinib kn-keyword=Osimertinib en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=6 article-no= start-page=315 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260527 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Limited Immune-Mediated Efficacy of Anti-PD-L1/VEGF in EGFR-TKI-Na?ve Egfr-Mutant Lung Cancer with Non-Inflamed Tumor Microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immune checkpoint inhibitors (ICIs) show limited efficacy in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma due to its non-inflamed tumor microenvironment (TME). While quadruple therapy combining chemotherapy, anti-programmed death-ligand 1 (PD-L1), and anti-vascular endothelial growth factor (VEGF) antibodies has shown inconsistent results in EGFR-tyrosine kinase inhibitor (TKI)-pretreated patients, whether anti-VEGF therapy can modulate the intrinsic non-inflamed TME remains unknown. We employed an EGFR-TKI-na?ve syngeneic Egfr-mutant mouse model and evaluated effects of anti-VEGF, anti-PD-L1, carboplatin, and paclitaxel as monotherapies and combinations, with TME analysis via immunohistochemistry (IHC), flow cytometry, and RNA sequencing. Anti-PD-L1 showed no antitumor effect, and adding anti-VEGF failed to convert the TME to an inflamed status. Although paclitaxel?but not carboplatin?combined with low-dose anti-VEGF inhibited tumor growth, adding anti-PD-L1 provided no benefit, indicating the anti-VEGF-A antibody evaluated here has a limited role in sensitizing tumors to anti-PD-L1 regardless of chemotherapy. CD8+ T-cell depletion did not attenuate the effect of paclitaxel plus low-dose anti-VEGF, and IHC and RNA sequencing revealed increased natural killer cell infiltration, suggesting a CD8+ T-cell-independent, innate immune mechanism. These findings provide preclinical evidence that the evaluated anti-VEGF has limited immunomodulatory activity in EGFR-TKI-na?ve Egfr-mutant tumors with a non-inflamed TME, and suggest immunotherapeutic strategies beyond CD8+ T-cell-mediated immunity warrant investigation. en-copyright= kn-copyright= en-aut-name=HirabaeAtsuko en-aut-sei=Hirabae en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkawaSachi en-aut-sei=Okawa en-aut-mei=Sachi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakasukaTakamasa en-aut-sei=Nakasuka en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishimuraJun en-aut-sei=Nishimura en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SugimotoMasamichi en-aut-sei=Sugimoto en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Product Research Department, Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=15 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=EGFR mutation kn-keyword=EGFR mutation en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=syngeneic mouse model kn-keyword=syngeneic mouse model en-keyword=antitumor immunity kn-keyword=antitumor immunity en-keyword=non-inflamed tumor kn-keyword=non-inflamed tumor en-keyword=VEGF kn-keyword=VEGF en-keyword=PD-L1 kn-keyword=PD-L1 END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=10 article-no= start-page=e70299 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Interstitial Lung Disease in Patients With Unresectable Stage III NSCLC Treated With Chemoradiotherapy Followed by Durvalumab in Japan: Analysis From the Multicenter Prospective AYAME Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Interstitial lung disease (ILD) is a concerning adverse event associated with immune checkpoint inhibitors, including durvalumab. This analysis of the multicenter AYAME study assessed the longterm safety of durvalumab, focusing on ILD.
Methods: AYAME enrolled patients prescribed durvalumab for unresectable stage III non-small cell lung cancer (NSCLC) after chemoradiotherapy (CRT) from July 2019 to December 2020 in Japan. Patients received durvalumab for ??12?months and were prospectively followed for 3?years. Incidence, severity, and management of ILD were examined. Multivariable logistic regression analysis was conducted to investigate the association of patient characteristics with grade ??2 ILD occurrence.
Results: Of 511 patients in the safety analysis population, ILD occurred in 383 patients (75.0%) from durvalumab initiation to subsequent treatment start; median time to occurrence was 44.0?days. ILD led to permanent durvalumab discontinuation in 121/383 patients (31.6%), dose interruption in 111/383 (29.0%), and corticosteroid intervention in 168/383 (43.9%). Grade ??2 ILD occurrence was higher in patients with volume of lung parenchyma that received 20?Gy (V20) ??25% versus Conclusions: This study of durvalumab for NSCLC after CRT in a real-world setting indicated factors associated with grade ??2 ILD and provided valuable insights into ILD management strategies. These findings may contribute to establishing effective approaches to minimize ILD risk in practice.
Trial Registration: UMIN000037090/NCT03995875 en-copyright= kn-copyright= en-aut-name=YamamotoNobuyuki en-aut-sei=Yamamoto en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KenmotsuHirotsugu en-aut-sei=Kenmotsu en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkdemirBurak en-aut-sei=Akdemir en-aut-mei=Burak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UematsuShinya en-aut-sei=Uematsu en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuiAyako en-aut-sei=Fukui en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KotoRyo en-aut-sei=Koto en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiwaraMasakazu en-aut-sei=Fujiwara en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwaoChikako en-aut-sei=Iwao en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitagawaHiroshi en-aut-sei=Kitagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshinoIchiro en-aut-sei=Yoshino en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GemmaAkihiko en-aut-sei=Gemma en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MitsudomiTetsuya en-aut-sei=Mitsudomi en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SaitoYoshinobu en-aut-sei=Saito en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= affil-num=2 en-affil=Division of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Oncology Medical, AstraZeneca K.K kn-affil= affil-num=5 en-affil=Oncology Medical, AstraZeneca K.K kn-affil= affil-num=6 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K kn-affil= affil-num=7 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K kn-affil= affil-num=8 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K kn-affil= affil-num=9 en-affil=Oncology Medical, AstraZeneca K.K kn-affil= affil-num=10 en-affil=Oncology Medical, AstraZeneca K.K kn-affil= affil-num=11 en-affil=Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital kn-affil= affil-num=12 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=13 en-affil=Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Pulmonary Medicine, Nippon Medical School Musashi Kosugi Hospital kn-affil= en-keyword=carcinoma kn-keyword=carcinoma en-keyword=chemoradiotherapy kn-keyword=chemoradiotherapy en-keyword=durvalumab kn-keyword=durvalumab en-keyword=interstitial kn-keyword=interstitial en-keyword=lung diseases kn-keyword=lung diseases en-keyword=non-small- cell lung kn-keyword=non-small- cell lung END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=1 article-no= start-page=160 end-page=173 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-Term Safety and Effectiveness of Durvalumab in Unresectable Stage III NSCLC in Japan: A Multicenter Prospective Study (AYAME) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Based on the PACIFIC trial results, durvalumab after chemoradiotherapy (CRT) is the standard of care for unresectable stage III NSCLC. However, few large-scale studies have prospectively evaluated its long-term effectiveness and safety, including subsequent treatment.
Methods: This multicenter, noninterventional study (AYAME) enrolled patients who were prescribed durvalumab for unresectable stage III NSCLC after CRT (July 2019?December 2020; 52 sites; Japan). Patients received durvalumab for a maximum of 12 months and were prospectively followed up for 3 years, including the post-durvalumab treatment period. Primary end points were real-world progression-free survival (rwPFS), the incidence of interstitial lung disease (ILD), and adverse events of special interest (AESIs).
Results: Of the 529 enrolled patients, 512 received durvalumab and 511 comprised the safety analysis population. The median time to onset of the first presentation or occurrence of ILD was 45.0 days. ILD of any grade occurred in 387 patients (75.7%) over the 3-year study period: grade 3, 57 (11.2%); grade 4, none (0.0%); and grade 5, 9 (1.8%). The most common AESIs of any grade during durvalumab treatment were thyroid dysfunction (12.5%), hepatic dysfunction (7.2%), and colitis (2.0%). No durvalumab treatment-related ILD or AESIs occurred during the post-treatment period. The median [95% confidence interval] rwPFS was 23.2 [18.2, 27.2] months in the effectiveness analysis population (n = 495). rwPFS rates were 62.5%, 54.6%, 49.4%, and 40.4% at 12, 18, 24, and 36 months, respectively.
Conclusions: This first and largest prospective, observational study demonstrated the long-term safety and effectiveness of durvalumab for unresectable stage III NSCLC after CRT in a real-world clinical setting.
Clinical Trial Registration: UMIN000037090 and NCT03995875 en-copyright= kn-copyright= en-aut-name=KenmotsuHirotsugu en-aut-sei=Kenmotsu en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaitoYoshinobu en-aut-sei=Saito en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UematsuShinya en-aut-sei=Uematsu en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkdemirBurak en-aut-sei=Akdemir en-aut-mei=Burak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuiAyako en-aut-sei=Fukui en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KotoRyo en-aut-sei=Koto en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiwaraMasakazu en-aut-sei=Fujiwara en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwaoChikako en-aut-sei=Iwao en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitagawaHiroshi en-aut-sei=Kitagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshinoIchiro en-aut-sei=Yoshino en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GemmaAkihiko en-aut-sei=Gemma en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MitsudomiTetsuya en-aut-sei=Mitsudomi en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamamotoNobuyuki en-aut-sei=Yamamoto en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Division of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Nippon Medical School, Musashi Kosugi Hospital kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Oncology Medical, AstraZeneca K.K. kn-affil= affil-num=5 en-affil=Oncology Medical, AstraZeneca K.K. kn-affil= affil-num=6 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K. kn-affil= affil-num=7 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K. kn-affil= affil-num=8 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K. kn-affil= affil-num=9 en-affil=Oncology Medical, AstraZeneca K.K. kn-affil= affil-num=10 en-affil=Oncology Medical, AstraZeneca K.K. kn-affil= affil-num=11 en-affil=Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital kn-affil= affil-num=12 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=13 en-affil=Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine and Faculty of Medicine & Hospital kn-affil= affil-num=14 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= en-keyword=Durvalumab kn-keyword=Durvalumab en-keyword=Chemoradiotherapy kn-keyword=Chemoradiotherapy en-keyword=Interstitial lung disease kn-keyword=Interstitial lung disease en-keyword=Real-world evidence kn-keyword=Real-world evidence en-keyword=Unresectable stage III NSCLC kn-keyword=Unresectable stage III NSCLC END start-ver=1.4 cd-journal=joma no-vol=234 cd-vols= no-issue= article-no= start-page=112260 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The eukaryotic host?microbe?phage?nutrition interplay determines the bacterial effectors of supplemental lysine’s health benefits: An experimental cellular senescence model of digestive conditions in older adults en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recently, the consumption of various forms of the nutritive amino acid lysine (e.g., nutraceuticals and dietary supplements) has increased, particularly among the elderly, as it cannot be synthesized by the human body and plays a crucial role in several cellular physiological processes, including intestinal calcium and iron absorption, proteinogenesis, and fatty acid metabolism. However, the biochemical and immunological events that occur within the eukaryotic host-microbe-phage-nutrition interaction, especially when high amounts of lysine are consumed in nutraceutical or dietary supplement form by the elderly due to age-related requirements, as well as the impact on gut bacteria-derived metabolites, have not yet been fully studied. We hypothesized that (1) within an infectious-inflamed digestive milieu, the metabolism of excess extracellular lysine differs between young and senescent digestive cells, and (2) phages within the milieu exhibit alterations in host-microbe cometabolite signal profiles. To address this, we examined how gut microbes and phages, key regulators of eukaryotic host physiology, influence the immunometabolism of excess lysine. By combining two models of young and senescent digestive cells, the pathogenic P. aeruginosa PAO1, the Pseudomonas phage KPP22, and the anti-inflammatory bacterium Intestinimonas butyriciproducens, and simulating the pathogenesis of the interactive process of excessive lysine ingestion, we developed a five-way screening approach to explore key cell readouts, including viability, integrity, and function of the epithelial barrier, as well as cellular immunometabolic responses to exogenous lysine supplementation in cultures under infectious inflammation. Our findings are consistent with the possibility that host?microbe?microbe interactions involving lysine utilization and cross-feeding may influence the effects of lysine supplementation. These effects, whether beneficial or detrimental, can depend on the bacterial community, including the presence of pathogenic or potentially beneficial bacteria, interactions with intestinal phages, and the physiological conditions and metabolic requirements of the host and individual microbial taxa. en-copyright= kn-copyright= en-aut-name=GhadimiDarab en-aut-sei=Ghadimi en-aut-mei=Darab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Bl?merSophia en-aut-sei=Bl?mer en-aut-mei=Sophia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KAYAAysel ?AH?N en-aut-sei=KAYA en-aut-mei=Aysel ?AH?N kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Kr?gerSandra en-aut-sei=Kr?ger en-aut-mei=Sandra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=R?ckenChristoph en-aut-sei=R?cken en-aut-mei=Christoph kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Sch?ferHeiner en-aut-sei=Sch?fer en-aut-mei=Heiner kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=de HeerGeraldine en-aut-sei=de Heer en-aut-mei=Geraldine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=JarczakDominik en-aut-sei=Jarczak en-aut-mei=Dominik kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuzakiShigenobu en-aut-sei=Matsuzaki en-aut-mei=Shigenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=BockelmannWilhelm en-aut-sei=Bockelmann en-aut-mei=Wilhelm kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= affil-num=2 en-affil=Faculty of Medicine, Christian-Albrechts-University of Kiel kn-affil= affil-num=3 en-affil=Department of Nutrition and Dietetics, Faculty of Health Sciences, Antalya Bilim University kn-affil= affil-num=4 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=5 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=6 en-affil=Laboratory of Molecular Gastroenterology & Hepatology, Christian-Albrechts-University & UKSH Campus Kiel kn-affil= affil-num=7 en-affil=University Center for Nutritional Medicine, University Medical Centre Hamburg-Eppendorf kn-affil= affil-num=8 en-affil=University Center for Nutritional Medicine, University Medical Centre Hamburg-Eppendorf kn-affil= affil-num=9 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University kn-affil= affil-num=11 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= en-keyword=Inflammaging kn-keyword=Inflammaging en-keyword=Lysine kn-keyword=Lysine en-keyword=Host cells kn-keyword=Host cells en-keyword=Phages kn-keyword=Phages en-keyword=Syntrophy kn-keyword=Syntrophy en-keyword=Cell senescence kn-keyword=Cell senescence END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260913 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical Significance of a Cell-Of-Origin-Based Classification in Pancreatic Ductal Adenocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with limited therapeutic options and poor clinical outcomes. Although PDAC has traditionally been thought to arise from ductal epithelial cells, recent studies using genetically engineered mouse models have demonstrated that acinar cells can also serve as a cell of origin, giving rise to tumors with distinct biological properties. Here, we investigated whether such lineage-specific differences are preserved in human PDAC. RNA sequencing was performed on resected specimens from 40 treatment-na?ve patients with PDAC, and tumors were classified into Acinar- and Ductal-subtypes using lineage-specific gene expression signatures derived from mouse models. This classification strategy was further applied to human PDAC cell lines, followed by in vitro drug sensitivity assays. Patients with Acinar-subtype tumors had significantly longer overall survival than those with Ductal-subtype tumors (median, 54.0 vs. 26.5?months; p? Methods: We retrospectively analyzed 225 nonagenarians undergoing surgical resection of CRC at 15 institutions between 2011 and 2022. Patients were stratified by GNRI-high/low status using two cutoffs: 98 (Cohort 1) and 86 (Cohort 2). Outcomes included postoperative complications, length of hospital stay, and overall survival (OS). Stabilized inverse-probability-of-treatment weighting (IPTW) was used to adjust for measured confounding.
Results: The median age was 92?years (female, 64.9%; colon cancer, 79.6%). GNRI-high patients had higher body mass index and albumin levels. Complication rates did not differ between the groups. After adjustment, GNRI-high patients in Cohort 1 had a shorter expected hospital stay (ratio 0.70, 95% CI 0.51?0.96; p?=?0.025) but no significant OS difference. In Cohort 2, GNRI-high patients had better OS (p? Conclusions: Preoperative GNRI was associated with hospital stay and OS in nonagenarians undergoing CRC surgery, although the OS association was significant only with the cohort-derived cutoff of 86, which requires external validation, and not with the literature-based cutoff of 98. The GNRI is a simple tool to stratify surgical risk and optimize perioperative nutritional status in this vulnerable population. en-copyright= kn-copyright= en-aut-name=ToshimaToshiaki en-aut-sei=Toshima en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakanagaSatoe en-aut-sei=Takanaga en-aut-mei=Satoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InadaRyo en-aut-sei=Inada en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhtaniTsuyoshi en-aut-sei=Ohtani en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaRyosuke en-aut-sei=Yoshida en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HoriNaoto en-aut-sei=Hori en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShigemitsuKaoru en-aut-sei=Shigemitsu en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoSumiharu en-aut-sei=Yamamoto en-aut-mei=Sumiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KubotaTetsushi en-aut-sei=Kubota en-aut-mei=Tetsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkanoYuka en-aut-sei=Okano en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NobuhisaTetsuji en-aut-sei=Nobuhisa en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaniguchiFumitaka en-aut-sei=Taniguchi en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IshikawaWataru en-aut-sei=Ishikawa en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsudaTatsuo en-aut-sei=Matsuda en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UmeokaTatsuo en-aut-sei=Umeoka en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=The Setouchi Colorectal Neoplasm Registration Study Group en-aut-sei=The Setouchi Colorectal Neoplasm Registration Study Group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Surgery, Kagawa Rosai Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Medical Development Field, Okayama University kn-affil= affil-num=5 en-affil=Department of Surgery, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Surgery, Saiseikai Okayama Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Okayama Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, Tottori Municipal Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, Tsuyama Chuo Hospital kn-affil= affil-num=10 en-affil=Department of Surgery, Okayama City Hospital kn-affil= affil-num=11 en-affil=Department of Surgery, Kobe Red Cross Hospital kn-affil= affil-num=12 en-affil=Department of Surgery, Onomichi City Hospital kn-affil= affil-num=13 en-affil=Department of Surgery, Himeji Red Cross Hospital kn-affil= affil-num=14 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=15 en-affil=Department of Surgery, Fukuyama City Hospital kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Surgery, Matsuda Hospital kn-affil= affil-num=18 en-affil=Department of Surgery, Matsuyama City Hospital kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=20 en-affil= kn-affil= en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=geriatric nutritional risk index kn-keyword=geriatric nutritional risk index en-keyword=oldest-old patients kn-keyword=oldest-old patients en-keyword=overall survival kn-keyword=overall survival en-keyword=surgical outcome kn-keyword=surgical outcome END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=1534891 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250227 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy in Japanese adults with growth hormone deficiency receiving weekly somapacitan or daily growth hormone: results from phase 3 REAL 1 trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Somapacitan is a long-acting growth hormone (GH) derivative approved for once-weekly treatment of adult GH deficiency (AGHD). This study aimed to evaluate the efficacy and safety of somapacitan and daily GH in Japanese individuals with AGHD.
Methods: This subgroup study included the 34-week main period of the multinational, randomized, parallel-group, phase 3 trial, REAL 1 (NCT02229851). Participants received once-weekly somapacitan or daily GH (Norditropin?), both administered subcutaneously. Investigators and trial sites were blinded. A total of 36 Japanese GH-na?ve individuals with AGHD were allocated to somapacitan or daily GH (excluding the placebo group of the global trial). Endpoints included change in truncal fat percentage to week 34 measured using dual-energy x-ray absorptiometry, as well as other body composition measures. Insulin-like growth factor I standard deviation score values were used for dose titration.
Results: In total, 36 Japanese individuals were included (18 and 18 in the somapacitan and daily GH group, respectively). 35 completed the main period (34 weeks). Mean (SD) change from baseline to week 34 in truncal fat percentage was -2.23 (2.50) %-points in the somapacitan group and -2.12 (4.21) %-points in the daily GH group. Other body composition measures also improved in both groups, including reduced visceral fat and increased lean body mass. Somapacitan was well tolerated, with a safety profile similar to daily GH.
Conclusions: In Japanese treatment-na?ve individuals with AGHD, once-weekly somapacitan demonstrated similar efficacy and safety to daily GH after 34 weeks of treatment. Somapacitan provides an effective alternative to daily GH in AGHD. en-copyright= kn-copyright= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RasmussenMichael H?jby en-aut-sei=Rasmussen en-aut-mei=Michael H?jby kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EndoTakaaki en-aut-sei=Endo en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Sv?rkeClaus en-aut-sei=Sv?rke en-aut-mei=Claus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaharaShigeyuki en-aut-sei=Tahara en-aut-mei=Shigeyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JohannssonGudmundur en-aut-sei=Johannsson en-aut-mei=Gudmundur kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Clinical Drug Development, Novo Nordisk A/S kn-affil= affil-num=3 en-affil=Medical Affairs Department, Novo Nordisk Pharma Ltd. kn-affil= affil-num=4 en-affil=Clinical Drug Development, Novo Nordisk A/S kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Nippon Medical School, Musashikosugi Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg and Department of Endocrinology, Diabetology, and Metabolism, Sahlgrenska University Hospital kn-affil= en-keyword=growth hormone kn-keyword=growth hormone en-keyword=adult growth hormone deficiency kn-keyword=adult growth hormone deficiency en-keyword=long-acting growth hormone kn-keyword=long-acting growth hormone en-keyword=somapacitan kn-keyword=somapacitan en-keyword=Japan kn-keyword=Japan END start-ver=1.4 cd-journal=joma no-vol=94 cd-vols= no-issue=1 article-no= start-page=1 end-page=18 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250311 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An XAI-based meta-parameter tuning for time-series forecasting en-subtitle= kn-subtitle= en-abstract= kn-abstract=How can we efficiently determine meta-parameter values for deep learning-based time-series forecasting given a time-series dataset? This paper introduces Xtune, an efficient and novel meta-parameter tuning method for deep learning-based time-series forecasting, leveraging explainable AI techniques. In particular, this study focuses on optimizing the window size for time-series forecasting. Xtune determines the optimal meta-parameter value for these methods and can also be applied to tune the window size for anomaly detection methods that utilize deep learning-based time-series forecasting. Extensive experiments on real-world datasets and forecasting methods demonstrate that Xtune efficiently identifies the optimal meta-parameter value and consistently outperforms the existing methods in terms of execution speed. en-copyright= kn-copyright= en-aut-name=NakagawaHiroyuki en-aut-sei=Nakagawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SumitaShimon en-aut-sei=Sumita en-aut-mei=Shimon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IidaRyuichi en-aut-sei=Iida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuchiyaTatsuhiro en-aut-sei=Tsuchiya en-aut-mei=Tatsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Osaka University kn-affil= affil-num=3 en-affil=Okayama University kn-affil= affil-num=4 en-affil=Osaka University kn-affil= en-keyword=Parameter optimization kn-keyword=Parameter optimization en-keyword=XAI kn-keyword=XAI en-keyword=Deep learning kn-keyword=Deep learning en-keyword=Time-series forecasting kn-keyword=Time-series forecasting en-keyword=Anomaly detection kn-keyword=Anomaly detection END start-ver=1.4 cd-journal=joma no-vol=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, Wroc?aw 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=14 cd-vols= no-issue=9 article-no= start-page=2110 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260921 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Virotherapy for Spinal and Spinal Cord Tumors: Current Evidence and Future Perspectives en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tumors of the spine and spinal cord, including primary and metastatic vertebral tumors, intramedullary gliomas, and refractory intradural lesions, are challenging to treat because curative local therapy is limited by the eloquent, nonregenerating neural tissue surrounding them. Oncolytic virotherapy may offer a rational alternative by combining tumor-selective oncolysis with the induction of systemic antitumor immunity, while sparing normal neural cells. This review summarizes the current field of oncolytic viruses, including adenovirus, herpes simplex virus, reovirus, and others, in the context of spinal and spinal cord tumors. Clinical data in the spine remain scarce; however, the rationale is based on histological evidence from sarcomas and other tumors, extensive glioma experience, including diffuse intrinsic pontine glioma, and preclinical activity in nerve sheath and meningioma models. We discuss the telomerase-specific oncolytic adenovirus OBP-301 and its derivatives, whose hTERT-driven replication provides histology-agnostic tumor selectivity, while sparing the telomerase-silent spinal cord. This telomerase dependence, however, limits activity against tumors that maintain telomeres through the alternative lengthening of telomeres (ALT) pathway, such as many osteosarcomas and some spinal cord astrocytomas. We also discuss delivery and safety within the confined spinal canal, combination strategies, and future directions, such as extracellular vesicle-mediated delivery and biomarker-guided patient selection. Although clinical translation to the spine will require dedicated preclinical and early-phase studies, virotherapy represents a promising, mechanistically grounded modality for these therapeutically challenging tumors. en-copyright= kn-copyright= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakatoriRyo en-aut-sei=Takatori en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamashitaKazutaka en-aut-sei=Yamashita en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoKenzaburo en-aut-sei=Matsumoto en-aut-mei=Kenzaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OdaYoshiaki en-aut-sei=Oda en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShinoharaKensuke en-aut-sei=Shinohara en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=oncolytic virotherapy kn-keyword=oncolytic virotherapy en-keyword=spinal cord tumor kn-keyword=spinal cord tumor en-keyword=spinal metastasis kn-keyword=spinal metastasis en-keyword=oncolytic adenovirus kn-keyword=oncolytic adenovirus en-keyword=OBP-301 kn-keyword=OBP-301 en-keyword=hTERT kn-keyword=hTERT en-keyword=telomerase kn-keyword=telomerase en-keyword=glioma kn-keyword=glioma en-keyword=blood?spinal cord barrier kn-keyword=blood?spinal cord barrier en-keyword=cancer immunotherapy kn-keyword=cancer immunotherapy END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=pcag119 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260928 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Disrupted FLOWERING LOCUS C alleles from weedy radish enhance the florigenic potential of rootstocks for graft-mediated floral induction in Brassicaceae en-subtitle= kn-subtitle= en-abstract= kn-abstract=Graft-mediated floral induction is a classical yet promising breeding technique that accelerates seed production and shortens generation time in crops. However, its application remains limited to a few species because floral induction is often unstable. Even among florally induced rootstocks, grafted scions can differ in their flowering response depending on rootstock genotype, but the genetic basis of this variation remains unclear. Here, using a Brassicaceae grafting model, we investigated two early-bolting radish (Raphanus sativus) accessions differing in their ability to induce flowering. We focused on a significant difference in FLOWERING LOCUS T (FT) expression between these accessions and identified two quantitative trait loci (QTLs) associated with FT levels. Transcriptomic and genomic analyses revealed that both QTLs harbored previously unreported disrupted alleles of FLOWERING LOCUS C (FLC) homologs, key floral repressors involved in vernalization, which showed reduced expression and produced defective transcripts. Grafting experiments demonstrated that these disrupted FLC alleles enhanced floral induction, with RsFLC1 having a major effect. Our results indicate that the FT expression threshold required for graft-mediated floral induction is higher than that for rootstock flowering itself and that this threshold is reached when FLC-mediated repression is substantially reduced. These alleles were inferred to have originated from weedy radish (Raphanus raphanistrum), likely contributing to early flowering in disturbed environments. This study suggests that exploring genetic variations in FT expression is an effective strategy to develop highly florigenic rootstocks, thereby broadening the application of graft-mediated floral induction in crop breeding. en-copyright= kn-copyright= en-aut-name=MotokiKo en-aut-sei=Motoki en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiSaki en-aut-sei=Kobayashi en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimuraKazusa en-aut-sei=Nishimura en-aut-mei=Kazusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KinoshitaYu en-aut-sei=Kinoshita en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KashimaMakoto en-aut-sei=Kashima en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UshijimaKoichiro en-aut-sei=Ushijima en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GotoTanjuro en-aut-sei=Goto en-aut-mei=Tanjuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YasubaKen-ichiro en-aut-sei=Yasuba en-aut-mei=Ken-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HosokawaMunetaka en-aut-sei=Hosokawa en-aut-mei=Munetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life and Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life and Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life and Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=5 en-affil=Faculty of Science, Department of Biomolecular Science, Toho University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life and Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life and Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life and Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Faculty of Agriculture, Kindai University kn-affil= en-keyword=Brassica oleracea kn-keyword=Brassica oleracea en-keyword=FLOWERING LOCUS C kn-keyword=FLOWERING LOCUS C en-keyword=FLOWERING LOCUS T kn-keyword=FLOWERING LOCUS T en-keyword=graft-mediated floral induction kn-keyword=graft-mediated floral induction en-keyword=vernalization kn-keyword=vernalization en-keyword=weedy radish (Raphanus raphanistrum) kn-keyword=weedy radish (Raphanus raphanistrum) END start-ver=1.4 cd-journal=joma no-vol=338 cd-vols= no-issue=16 article-no= start-page=1641 end-page=1650 dt-received= dt-revised= dt-accepted= dt-pub-year=2003 dt-pub=20030729 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Stereoselectivity in deoxygenation of 5-hydroxy-5-phosphinyl-hexofuranoses (α-hydroxyphosphonates) en-subtitle= kn-subtitle= en-abstract= kn-abstract=The addition of dimethyl phosphonate to six different hexofuranos-5-uloses in the presence of DBU, followed by esterification with methoxalyl chloride and then radical reduction, afforded 5-deoxy-5-dimethoxyphosphinyl-d- and l-hexofuranoses. The stereoselectivity of the deoxygenation and possible transition-state models are discussed. en-copyright= kn-copyright= en-aut-name=HanayaTadashi en-aut-sei=Hanaya en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugiyamaKen-ichi en-aut-sei=Sugiyama en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawamotoHeizan en-aut-sei=Kawamoto en-aut-mei=Heizan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoHiroshi en-aut-sei=Yamamoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= en-keyword=Phospho sugar kn-keyword=Phospho sugar en-keyword=Deoxygenation kn-keyword=Deoxygenation en-keyword=α-Hydroxyphosphonate kn-keyword=α-Hydroxyphosphonate END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e77909 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260927 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SPRED2 Negatively Regulates CD8+ T Cell-Mediated Antitumor Immunity in Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Activation of the RAS/RAF/ERK pathway is crucial for adaptive immunity. Here, we provide evidence that Sprouty-related EVH1 domain containing 2 (SPRED2), an endogenous inhibitor of this pathway, negatively regulates CD8+ T cell-mediated antitumor immunity in breast cancer. In EO771 and 4T1 mouse models, Spred2?/? mice exhibit reduced tumor growth, with lower endpoint lung metastatic burden in the 4T1 model, accompanied by increased T-cell infiltration and activation. Spred2?/? T cells show enhanced cytokine expression, proliferation,survival, in vitro cytotoxicity, and memory-like phenotypes, particularly among CD8+ T cells. Adoptive transfer of Spred2?/? CD8+ T cells into tumor-bearing wild-type hosts similarly reduces endpoint lung metastatic burden. MEK inhibition with U0126 attenuates increased interferon-gamma and granzyme B expression in Spred2?/? CD8+ T cells. Transcriptomic analyses reveal an inverse correlation between SPRED2 expression and antitumor CD8+ T cell states in both humans and mice. In tumor-infiltrating T cells from patients with breast cancer, SPRED2low T cells show enriched effector and cytotoxicity programs and are associated with “immune-hot” tumors, whereas survival associations vary with CD8+ T cell context. Collectively, these findings suggest that SPRED2 functions as a cell-intrinsic negative regulator of CD8+ T-cell activation and highlight its potential as a therapeutic target to enhance T cell?based cancer immunotherapy. en-copyright= kn-copyright= en-aut-name=TianMiao en-aut-sei=Tian en-aut-mei=Miao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZhaoKun en-aut-sei=Zhao en-aut-mei=Kun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiChunning en-aut-sei=Li en-aut-mei=Chunning kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GaoTong en-aut-sei=Gao en-aut-mei=Tong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=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=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Advanced International and Information Dentistry, Faculty 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= affil-num=9 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=CD8+ T cells kn-keyword=CD8+ T cells en-keyword=immunotherapy kn-keyword=immunotherapy en-keyword=MAPK/ERK kn-keyword=MAPK/ERK en-keyword=tumor microenvironment kn-keyword=tumor microenvironment END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=2 article-no= start-page=323 end-page=337 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Unraveling Causality: Innovations in Epidemiologic Methods en-subtitle= kn-subtitle= en-abstract= kn-abstract=For several decades, the counterfactual model and the sufficient cause model have shaped our understanding of causation in biomedical science and, more recently, the link between these two models has enabled us to obtain a deeper understanding of causality. In this article, I provide a brief overview of these fundamental causal models using a simple example. The counterfactual model focuses on one particular cause or intervention and gives an account of the various effects of that cause. By contrast, the sufficient cause model considers sets of actions, events, or states of nature which together inevitably bring about the outcome under consideration. In other words, the counterfactual framework addresses the question “what if?” while the sufficient cause framework addresses the question “why does it happen?” Although these two models are distinct and address different causal questions, they are closely related and used to elucidate the same cause-effect relationships. Importantly, the sufficient cause model makes clear that causation is a multifactorial phenomenon, and it is a “finer” model than the counterfactual model; an individual is of one and only one response type in the counterfactual framework, whereas an individual may be at risk of none, one, or several sufficient causes. Understanding the link between the two causal models can provide greater insight into causality and can facilitate the use of each model in appropriate contexts, highlighting their respective strengths. I will briefly present three topics of interest from our research: the relationship between the concepts of confounding and of covariate balance; distinctions between attributable fractions and etiologic fractions; and the identification of operating mediation and mechanism. It is important to scrutinize observed associations in a complementary manner, using both the counterfactual model and the sufficient cause model, employing both inductive and deductive reasoning. This holistic approach will better help us to unravel causality. en-copyright= kn-copyright= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=attributable fraction kn-keyword=attributable fraction en-keyword=causal inference kn-keyword=causal inference en-keyword=confounding kn-keyword=confounding en-keyword=counterfactual model kn-keyword=counterfactual model en-keyword=covariate balance kn-keyword=covariate balance en-keyword=etiologic fraction kn-keyword=etiologic fraction en-keyword=mediation kn-keyword=mediation en-keyword=sufficient cause model kn-keyword=sufficient cause model END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=9 article-no= start-page=218 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260829 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=First-Order Wall-Slip-Induced Departure from Inverse-Cubic Scaling of Levitation-Pressure RMS in a Push?Pull Levitation Stage en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study clarifies how rarefaction-induced wall slip in a thin gas film affects the established inverse-cubic scaling law for the spatial nonuniformity of levitation pressure in a push?pull levitation stage. The levitation force in this stage is generated by the combined action of blowing and suction. The continuum-based stress description is retained, and only the wall boundary condition is changed from the no-slip condition to a first-order slip condition. Three-dimensional incompressible unsteady Stokes simulations in a thin-gap unit-cell model are combined with a lubrication-theory scaling analysis. The effects of levitation height, blowing-velocity distribution, port-radius ratio, and computational-domain width are examined systematically. The results show that wall slip has only a minor influence at relatively large levitation heights. As the levitation height decreases, however, rarefaction-induced slip increases the flow-rate conductance. Consequently, the intensity of the spatial variation in levitation pressure is systematically reduced below that predicted by the no-slip inverse-cubic scaling law. This departure is well described by a correction relation derived from the lubrication approximation and remains robust against changes in the prescribed blowing-velocity distribution and geometric conditions. These findings provide an incompressible baseline for predicting levitation-pressure nonuniformity within the nominal gap-based Knudsen-number range examined here. en-copyright= kn-copyright= en-aut-name=UmesakiEisuke en-aut-sei=Umesaki en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiHiroki en-aut-sei=Suzuki en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakamotoJunji en-aut-sei=Sakamoto en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KouchiToshinori en-aut-sei=Kouchi en-aut-mei=Toshinori 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=push?pull levitation kn-keyword=push?pull levitation en-keyword=wall slip kn-keyword=wall slip en-keyword=rarefaction kn-keyword=rarefaction en-keyword=lubrication approximation kn-keyword=lubrication approximation en-keyword=pressure RMS kn-keyword=pressure RMS en-keyword=thin gas film kn-keyword=thin gas film en-keyword=Knudsen number kn-keyword=Knudsen number END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=18 article-no= start-page=8117 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260912 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Salivary miR-324-5p Is Associated with Periodontal Inflamed Surface Area in People Living with HIV Receiving Antiretroviral Therapy: A Case?Control Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontitis is a common inflammatory disease that affects the tooth-supporting tissues. Salivary microRNA (miRNA) expression in extracellular vesicles (EVs) can reflect periodontal status. Both the prevalence and severity of periodontitis are higher in people with human immunodeficiency virus (PWH). This study aimed to identify miRNA in salivary EVs associated with periodontitis in PWH receiving antiretroviral therapy (ART). The case group comprised PWH with periodontitis undergoing ART, while the control group included individuals with periodontitis but without HIV infection. The study was conducted in two phases. In the first phase, a specific miRNA was identified in the case group using next-generation sequencing analysis, resulting in the selection of hsa-miR-324-5p as a candidate marker of periodontitis. In the second phase, the association between miRNA expression of hsa-miR-324-5p and periodontal status in the case group was evaluated using real-time-quantitative PCR (RT-qPCR). RT-qPCR analysis demonstrated that hsa-miR-324-5p expression was significantly associated with periodontal inflamed surface area (PISA). Bioinformatic analysis identified 10 potential hub genes for hsa-miR-324-5p that are involved in protein kinase binding and are associated with the adherens junction pathway, that may be contributing to the pathogenesis of periodontitis. Salivary hsa-miR-324-5p derived from EVs may be associated with the severity of periodontitis among PWH receiving ART. en-copyright= kn-copyright= en-aut-name=NurhamimMohammad en-aut-sei=Nurhamim en-aut-mei=Mohammad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokoiAya en-aut-sei=Yokoi en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaruyamaTakayuki en-aut-sei=Maruyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=miR-324-5p kn-keyword=miR-324-5p en-keyword=saliva kn-keyword=saliva en-keyword=marker kn-keyword=marker en-keyword=HIV kn-keyword=HIV en-keyword=periodontitis kn-keyword=periodontitis en-keyword= extracellular vesicles kn-keyword= extracellular vesicles en-keyword=inflammation kn-keyword=inflammation END start-ver=1.4 cd-journal=joma no-vol=604 cd-vols= no-issue=18 article-no= start-page=7640 end-page=7662 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260820 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Integrative simulation analysis of myocardial ischaemia?reperfusion injury en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cardiac ischaemia, reduced coronary blood flow, causes significant damages to the heart, and paradoxically reperfusion, restored flow after ischaemia, often results in more severe injury. Although the mechanisms underlying cardiac ischaemia?reperfusion injury have been intensively investigated, effective therapeutic strategies applicable during reperfusion to mitigate this damage have not been established yet. To obtain more insights into the mechanisms underlying ischaemia?reperfusion injury, and to explore effective methods to relieve reperfusion injury, we developed a comprehensive mathematical model of ventricular myocyte, implementing excitation?contraction (E?C) coupling, cytosolic and mitochondrial pH regulation, pH dependence of major components of E?C coupling and cellular energy metabolism, including mitochondrial oxidative phosphorylation. The mathematical model successfully reproduced experimentally observed findings on cardiac ischaemia?reperfusion injury, such as intracellular and extracellular acidosis, cytosolic Na+ overload, cytosolic Ca2+ overload, mitochondrial dysfunction, action potential shortening and contraction failure. It was found that the reperfusion-induced exacerbation of Na+i, Ca2+i overloads was mainly caused by insufficient production of NADH, which is used in mitochondrial oxidative phosphorylation to synthesize ATP for Na+/K+ pump and sarcoplasmic/endoplasmic reticulum Ca2+ pump (SERCA) to expel accumulated cytosolic Na+ and Ca2+, respectively. It was suggested that the preservation of mitochondrial NADH production, attenuation of ATP consumption via SERCA or contraction for a short period or activation of the Na+/K+ pump during reperfusion mitigates reperfusion injury. en-copyright= kn-copyright= en-aut-name=ShimayoshiTakao en-aut-sei=Shimayoshi en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeuchiAyako en-aut-sei=Takeuchi en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuokaSatoshi en-aut-sei=Matsuoka en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Center for Artificial Intelligence and Mathematical Data Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Physiology and Biophysics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Integrative and Systems Physiology, Faculty of Medical Sciences, University of Fukui kn-affil= en-keyword=computational modelling kn-keyword=computational modelling en-keyword=heart kn-keyword=heart en-keyword=ischaemia kn-keyword=ischaemia en-keyword=mitochondria kn-keyword=mitochondria en-keyword=reperfusion kn-keyword=reperfusion 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=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=165 cd-vols= no-issue=10 article-no= start-page=104508 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260911 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Scaled-charge ion force field optimized for individual ion partial molar volumes in water en-subtitle= kn-subtitle= en-abstract= kn-abstract=We present an ion partial molar volume force field for common monovalent and divalent ionic species, including Li+, Na+, K+, Cs+, Mg2+, Ca2+, F?, Cl?, Br?, I?, OH?, and H3O+. When combined with the TIP4P/2005 water model, the force field enables quantitative investigations of ion-specific effects in both bulk and interfacial properties. The iPMV force field is developed based on a single guiding principle: the ion?water interaction parameters are optimized such that the experimental partial molar volume of each individual ion at infinite dilution?determined via the ultrasonic vibrational potential method?is reproduced by construction. An exception is made for the hydronium ion, for which we also provide an alternative interface-optimized model. The force field employs a charge scaling factor of 0.75 and adopts the Lorentz?Berthelot combining rules for cross-Lennard-Jones interactions, with specific modifications for divalent cations. A distinctive feature of the iPMV force field is that, despite its straightforward design, a single set of ion parameters consistently reproduces a wide range of experimental properties?from volumetric and interfacial properties to salting-out/in effects and transport coefficients. This robust performance suggests a fundamental correlation between the partial molar volumes of individual ions and the broader physical properties of aqueous electrolyte solutions. en-copyright= kn-copyright= en-aut-name=TairaAoi en-aut-sei=Taira en-aut-mei=Aoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatsutoHiroyuki en-aut-sei=Katsuto en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakaoKanon en-aut-sei=Nakao en-aut-mei=Kanon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SumiTomonari en-aut-sei=Sumi en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KogaKenichiro en-aut-sei=Koga en-aut-mei=Kenichiro 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=Graduate School of Engineering, Muroran Institute of Technology kn-affil= affil-num=5 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=1 article-no= start-page=100037 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Older patients with LBCL show comparable outcomes to younger patients and product-specific profiles in CAR-T therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a key treatment option for patients with relapsed or refractory large B-cell lymphoma (LBCL). However, data on its effectiveness and safety in older populations remain limited, particularly in real-world clinical practice. Moreover, comparative outcomes among different CAR-T products across age groups have not yet been fully characterized. We conducted a nationwide retrospective cohort study using data from the Japanese Society for Transplantation and Cellular Therapy. A total of 908 patients who received CAR-T therapy between January 2019 and September 2024 were included. Patients were categorized as younger (aged <65 years) or older (aged ?65 years). Subgroup analyses were performed by CAR-T product (tisagenlecleucel [tisa-cel], lisocabtagene maraleucel [liso-cel], and axicabtagene ciloleucel [axi-cel]). In univariate analysis, 1-year overall survival (OS) and progression-free survival (PFS) were comparable between younger and older patients (OS, 69.4% vs 65.7% [P = .40]; PFS, 47.9% vs 54.1% [P = .17]). In multivariate analysis, age ?65 years showed no significant association with OS (hazard ratio, 0.88; 95% confidence interval, 0.65-1.21; P = .44). The incidence of immune effector cell?associated neurotoxicity syndrome was significantly higher in older patients (12.7% vs 7.0%; P = .005). Compared with tisa-cel, axi-cel and liso-cel were associated with superior PFS, predominantly in younger patients. Among older patients, axi-cel was associated with higher nonrelapse mortality rate than tisa-cel. CAR-T therapy is feasible and effective for older patients with LBCL. These findings support age-adapted treatment strategies that consider both the efficacy and toxicity of each product. en-copyright= kn-copyright= en-aut-name=ShibataSho en-aut-sei=Shibata en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AraiYasuyuki en-aut-sei=Arai en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KandaJunya en-aut-sei=Kanda en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KajiDaisuke en-aut-sei=Kaji en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MinakataDaisuke en-aut-sei=Minakata en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitawakiToshio en-aut-sei=Kitawaki en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimadaKazuyuki en-aut-sei=Shimada en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimoyamaTatsu en-aut-sei=Shimoyama en-aut-mei=Tatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshiharaSatoshi en-aut-sei=Yoshihara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MakitaShinichi en-aut-sei=Makita en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamamotoGo en-aut-sei=Yamamoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SakaidaEmiko en-aut-sei=Sakaida en-aut-mei=Emiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakashimaYasuhiro en-aut-sei=Nakashima en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YoshidaAkiyo en-aut-sei=Yoshida en-aut-mei=Akiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=UmezawaYoshihiro en-aut-sei=Umezawa en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KatoJun en-aut-sei=Kato en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KimHaryoon en-aut-sei=Kim en-aut-mei=Haryoon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KataokaKeisuke en-aut-sei=Kataoka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=GotoHideki en-aut-sei=Goto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Hematology, Kyoto University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology, Kyoto University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Kyoto University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Toranomon Hospital kn-affil= affil-num=5 en-affil=Division of Hematology, Department of Medicine, Jichi Medical University kn-affil= affil-num=6 en-affil=Department of Hematology, Kyoto University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Nagoya University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=9 en-affil=Department of Hematology, Hyogo Medical University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, National Cancer Center Hospital, Tokyo kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology, Toranomon Hospital kn-affil= affil-num=13 en-affil=Department of Hematology, Chiba University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology, Osaka Metropolitan University Hospital kn-affil= affil-num=15 en-affil=Division of Transfusion Medicine, Kanazawa University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology, Institute of Science Tokyo Hospital kn-affil= affil-num=17 en-affil=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=18 en-affil=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=19 en-affil=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=20 en-affil=Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital kn-affil= affil-num=21 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=22 en-affil=Department of Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=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=34 cd-vols= no-issue=2 article-no= start-page=118 end-page=129 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Factors promoting students’ application of health checkup reports: analysis using health literacy skills framework kn-title=中・高・大学生の健診結果活用の促進要因?ヘルスリテラシースキルフレームワークを用いた検討? en-subtitle= kn-subtitle= en-abstract=Objective: This study aimed to clarify the factors associated with the application of health checkup reports and their interrelationships using a health literacy skills framework.
Methods: An anonymous, self-administered questionnaire survey was administered 493 middle school, 360 high school and 297 first-year university students. The contents included “Application of Health Checkup Reports,” “Health Interest,” “Health Literacy (HL),” “Readability of The Health Checkup Report,” “Reading Comprehension of The Report,” and “Decision-making Balance.” The hypothetical model was tested using a multi group simultaneous path analysis by school type and sex.
Results: The revised model, in which four additional paths were added, showed a good fit across all school types and sex. The paths from “Readability” to “Reading comprehension,” “Reading comprehension” to “Decision-making,” “Decision-making” to “Application,” “Health Interest” to “Reading comprehension,” “Decision-making,” and “Application,” “HL” to “Application” were significant across all school types. Conversely, the paths from “Health Interest” and “Readability” to “HL,” and “HL” to “Reading comprehension” and “Decision-making,” were significant only among middle and high school students.
Conclusion: Making the results easier to understand, enhancing reading comprehension and recognition of the pros of health checkups, and reducing recognition of the cons might effectively promote the application of health checkup reports among students. kn-abstract=目的：学校健康診断結果活用（以下，活用）と関連要因及び相互の関連性をヘルスリテラシースキルフレームワークを用いて明らかにすることを目的とした．
方法：中学生493名，高校生360名，大学1年生297名を対象に無記名自記式質問紙調査を行った．調査内容は活用と，健康への関心，ヘルスリテラシー（以下，HL），健診結果に対する認識，健診結果の読解力（以下，読解力），意思決定バランスとした．これらの関連性を示す仮説モデルを校種，性別の多母集団同時パス解析で検証した．
結果：仮説モデルに4つのパスを追加した修正モデルで，校種，性別いずれにおいても配置不変モデルで良好な適合度を得た．健診結果に対する認識から読解力，読解力から意思決定バランス，意思決定バランスから活用，健康への関心から読解力，意思決定バランス，活用へのパス及び，HLから活用へのパスは全ての校種において有意であった．健康への関心と結果に対する認識からHL，HLから読解力，意思決定バランスへのパスは中・高校生のみで有意であった．
結論：中・高・大学生の健診結果活用を促すためには，健診結果を分かりやすくすること，健診結果の読解力及び意思決定バランスの向上，すなわち恩恵の認識の向上と，負担の認識の軽減が有効であり，その際に対象者の健康への関心とHLの程度を考慮する必要性が示唆された． en-copyright= kn-copyright= en-aut-name=ONISHIHitomi en-aut-sei=ONISHI en-aut-mei=Hitomi kn-aut-name=大西瞳 kn-aut-sei=大西 kn-aut-mei=瞳 aut-affil-num=1 ORCID= en-aut-name=NISHIOKANobuki en-aut-sei=NISHIOKA en-aut-mei=Nobuki kn-aut-name=西岡伸紀 kn-aut-sei=西岡 kn-aut-mei=伸紀 aut-affil-num=2 ORCID= en-aut-name=ITOTakehiko en-aut-sei=ITO en-aut-mei=Takehiko kn-aut-name=伊藤武彦 kn-aut-sei=伊藤 kn-aut-mei=武彦 aut-affil-num=3 ORCID= affil-num=1 en-affil=The Joint Graduate School (Ph.D. Program) in Science of School Education, Hyogo University of Teacher Education kn-affil=兵庫教育大学大学院連合学校教育学研究科 affil-num=2 en-affil=Faculty of Psychology and Collaboration, Kyoto Women’s University kn-affil=京都女子大学心理共生学部 affil-num=3 en-affil=Graduate School of Education, Okayama University kn-affil=岡山大学大学院教育学研究科 en-keyword=読みやすさ (readability) kn-keyword=読みやすさ (readability) en-keyword=読解力 (reading comprehension) kn-keyword=読解力 (reading comprehension) en-keyword=意思決定バランス (decision balance) kn-keyword=意思決定バランス (decision balance) en-keyword=健康への関心 (health interest) kn-keyword=健康への関心 (health interest) en-keyword=ヘルスリテラシー (health literacy) kn-keyword=ヘルスリテラシー (health literacy) END start-ver=1.4 cd-journal=joma no-vol=49 cd-vols= no-issue=6 article-no= start-page=983 end-page=988 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260620 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of Deuterated Drugs on Safety: Insights from Pharmacovigilance Data Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Tetrabenazine (TBZ), a vesicular monoamine transporter 2 inhibitor, is commonly used to manage chorea; however, it may exhibit fluctuating plasma levels and elicit frequent adverse events. In this study, we aimed to clarify the effects of TBZ deuteration on its safety profile. We compared the safety profiles of TBZ and deutetrabenazine (DTBZ) in real-world clinical practice using disproportionality analysis and the large-scale pharmacovigilance database, VigiBase?the WHO’s global database of adverse drug reactions. Adverse event signals were assessed using the information component (IC). Seriousness was classified according to clinical outcome, and time to onset (TTO) was analyzed for selected events. TBZ showed signals for disorientation, dystonia, and sleep disorders (IC025 > 0), whereas DTBZ did not. Serious adverse events were reported in 54.7% of TBZ cases and 37.9% of DTBZ cases. The TTO of sleep disorder was also evaluated; however, the number of cases with available TTO information was limited. DTBZ showed fewer adverse event signals and a lower proportion of serious adverse events than TBZ. These findings suggest potential differences in the safety profiles of the two drugs, which may influence tolerability in the treatment of HD. en-copyright= kn-copyright= en-aut-name=KitagawaKohei en-aut-sei=Kitagawa en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NawaHideki en-aut-sei=Nawa en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsaiShota en-aut-sei=Asai en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwataNaohiro en-aut-sei=Iwata en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NiimuraTakahiro en-aut-sei=Niimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GodaMitsuhiro en-aut-sei=Goda en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshizawaKeisuke en-aut-sei=Ishizawa en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama Psychiatric Medical Center kn-affil= affil-num=2 en-affil=Department of Pharmacy, Faculty of Pharmacy, Shujitsu University kn-affil= affil-num=3 en-affil=Department of Pharmacy, Faculty of Pharmacy, Shujitsu University kn-affil= affil-num=4 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=6 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=8 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences kn-affil= en-keyword=deuterated drug kn-keyword=deuterated drug en-keyword=VigiBase kn-keyword=VigiBase en-keyword=heavy drug kn-keyword=heavy drug en-keyword=safety advantage kn-keyword=safety advantage en-keyword=pharmacovigilance analysis kn-keyword=pharmacovigilance analysis END start-ver=1.4 cd-journal=joma no-vol=34 cd-vols= no-issue=8 article-no= start-page=809 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=Machine learning approaches to predict early cardiac immune-related adverse events in patients receiving immune checkpoint inhibitors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Immune checkpoint inhibitor (ICI)?induced cardiac immune-related adverse events (cardiac irAEs) are rare yet serious complications. Clinical assessment tools to identify at-risk patients would allow for more effective prevention strategies, thus improving clinical outcomes. We constructed various machine learning (ML) models to predict these events among patients receiving ICI therapy.
Methods A cohort of patients receiving ICI therapy from 2010 to 2023 was identified from the TriNetX database. Cardiac irAEs were defined as the occurrence of relevant diagnosis codes within 90 days of ICI initiation, with corresponding hospital visits. We created ML models to predict these events, including elastic net logistic regression and multiple tree-based approaches (gradient boosted trees and random forest). We evaluated model performance with different performance measures and utilized assigned risk scores to stratify risk of cardiac irAEs into low, medium, and high-risk tiers.
Results We identified 61,117 patients receiving ICI therapy, with nearly 2% of patients experiencing cardiac irAEs. Model performance on testing data was comparable with all approaches (AUC?=?0.71?0.72, balanced accuracy?=?65?66%). Each model emphasized distinct features to make classifications, as observed with feature importance and SHAP values. Comparing cardiac irAE rates among assigned risk strata, patients identified as high risk were significantly more likely to experience cardiac irAEs compared to lower tiers.
Conclusion Our preliminary exploration of ML methods demonstrated the potential for risk assessment tools to predict rare cardiac irAEs in patients receiving ICI therapy. Follow-up studies can implement time series approaches to harness longitudinal data that incorporates real-time labs, new diagnoses, and new therapy, to refine predictions further. en-copyright= kn-copyright= en-aut-name=SayerMichael en-aut-sei=Sayer en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChangPeter D. en-aut-sei=Chang en-aut-mei=Peter D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoReina en-aut-sei=Yamamoto en-aut-mei=Reina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagasakaMisako en-aut-sei=Nagasaka en-aut-mei=Misako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NaqviAli A. en-aut-sei=Naqvi en-aut-mei=Ali A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PatelPranav M. en-aut-sei=Patel en-aut-mei=Pranav M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OzakiAya F. en-aut-sei=Ozaki en-aut-mei=Aya F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= affil-num=2 en-affil=School of Medicine, Pathology & Laboratory Medicine, University of California kn-affil= affil-num=3 en-affil=Department of Pharmacy, Medical Development Field, Okayama University kn-affil= affil-num=4 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Division of Hematology and Oncology, University of California kn-affil= affil-num=6 en-affil=Mary & Steve Wen Cardiovascular Division, Department of Medicine, University of California kn-affil= affil-num=7 en-affil=Mary & Steve Wen Cardiovascular Division, Department of Medicine, University of California kn-affil= affil-num=8 en-affil=Department of Pharmacy, Medical Development Field, Okayama University kn-affil= affil-num=9 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors en-keyword=Immune-related adverse events kn-keyword=Immune-related adverse events en-keyword=Myocarditis kn-keyword=Myocarditis en-keyword=Pericarditis kn-keyword=Pericarditis en-keyword=Machine learning kn-keyword=Machine learning en-keyword=Risk assessment tools kn-keyword=Risk assessment tools END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page= 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=Seizures associated with clozapine augmentation by other antipsychotics: a pharmacovigilance?pharmacodynamic analysis using VigiBase en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Clozapine is associated with a high risk of central nervous system abnormalities. However, seizure risk related to interactions between clozapine and other antipsychotics remains poorly characterized, and the pharmacological mechanisms underlying these seizures are unclear. Objectives: We aimed to evaluate safety signals for seizures associated with clozapine augmentation by other antipsychotics and analyze the relationship between these signals and neurotransmitter receptor occupancy profiles.
Design: A pharmacovigilance?pharmacodynamic analysis using a spontaneous reporting system.
Methods: This pharmacovigilance study used VigiBase, an adverse drug reaction database maintained by the World Health Organization. Drug?drug interactions (DDIs) between clozapine and other antipsychotics were assessed using the Ω shrinkage measure model. The association between DDI signals and neurotransmitter receptor occupancy was evaluated using linear regression. Robustness was tested using four frequency statistical models: additive, multiplicative, combination risk ratio, and chi-square statistic models. Results: Of 38,758,077 reports in VigiBase between 1990 and 2024, 230,371 involved clozapine. Among antipsychotics classified under ATC code N05A, DDIs with clozapine were detected for amisulpride, chlorpromazine, haloperidol, lurasidone, olanzapine, penfluridol, risperidone, sulpiride, zotepine, and zuclopenthixol. A significant association between dopamine D4 receptor occupancy and the point estimates of signal values was observed in the Ω shrinkage measure model (β?=?0.295, 95% confidence interval: 0.119?0.471, p?=?0.002) and replicated across all frequency statistical models.
Conclusions: These findings suggest a potential role of dopamine D4 receptor occupancy in seizures associated with clozapine augmentation by other antipsychotics. Further large-scale epidemiological studies are needed to validate these findings. en-copyright= kn-copyright= en-aut-name=HatanoMasakazu en-aut-sei=Hatano en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KandaMasaya en-aut-sei=Kanda en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KosekiTakenao en-aut-sei=Koseki en-aut-mei=Takenao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakaiTsuyoshi en-aut-sei=Nakai en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriiRina en-aut-sei=Horii en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshiharaNozomi en-aut-sei=Yoshihara en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SaitoTakeo en-aut-sei=Saito en-aut-mei=Takeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakechiKenshi en-aut-sei=Takechi en-aut-mei=Kenshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EsumiSatoru en-aut-sei=Esumi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=YamadaShigeki en-aut-sei=Yamada en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine kn-affil= affil-num=2 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pharmacy, Asahikawa Medical University Hospital kn-affil= affil-num=4 en-affil=Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine kn-affil= affil-num=5 en-affil=Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine kn-affil= affil-num=6 en-affil=Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine kn-affil= affil-num=7 en-affil=Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine kn-affil= affil-num=8 en-affil=Department of Psychiatry, Fujita Health University School of Medicine kn-affil= affil-num=9 en-affil=Department of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama University kn-affil= affil-num=10 en-affil=The Faculty of Pharmaceutical Sciences, Kobe Gakuin University kn-affil= affil-num=11 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biological Resectability in Colorectal Liver Metastases: A Nomogram‐Based Continuous Risk Model to Define Borderline Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Resectability in colorectal liver metastases (CRLM) is traditionally defined by technical feasibility; however, a biologically based definition of borderline resectable disease has not been established. We evaluated the prognostic impact of KRAS mutation and developed a model for biological risk stratification.
Methods: This multi-institutional retrospective study included 584 patients undergoing initial hepatectomy for CRLM. The impact of KRAS mutation was assessed according to primary tumor sidedness and tumor burden score (TBS). A nomogram predicting overall survival (OS) was constructed using independent prognostic factors and compared with established clinical risk scores.
Results: KRAS mutation was identified in 36.8% of patients and was associated with worse OS (median survival: 47.3 vs. 70.6?months, p?=?0.0006) and recurrence-free survival. This adverse impact was observed in left-sided tumors but not in right-sided tumors. TBS stratified prognosis in KRAS wild-type but not in mutant cases, suggesting that tumor biology may outweigh morphology. A nomogram incorporating KRAS status, TBS, CA19-9, primary nodal status, and extrahepatic disease demonstrated improved discriminatory ability compared with conventional models and stratified recurrence patterns, including extrahepatic recurrence.
Conclusions: The prognostic impact of KRAS mutation depends on tumor sidedness and is independent of tumor morphology. Our nomogram provides a continuous biological risk assessment and may facilitate biological risk stratification and support future refinement of the concept of biologically borderline resectable CRLM. en-copyright= kn-copyright= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo 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=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KojimaToru en-aut-sei=Kojima en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KoujimaTakeshi en-aut-sei=Koujima en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=SatohDaisuke en-aut-sei=Satoh en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Innovative Clinical Medicine, Medical Development Field, Okayama University 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 Surgery, Okayama Saiseikai General Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Himeji Red Cross Hospital kn-affil= affil-num=6 en-affil=Department of Surgery, Tenwakai Matsuda Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Hiroshima Citizens Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=biology kn-keyword=biology en-keyword=borderline resectable kn-keyword=borderline resectable en-keyword=colorectal liver metastases kn-keyword=colorectal liver metastases en-keyword=genetic profile kn-keyword=genetic profile en-keyword=KRAS kn-keyword=KRAS en-keyword=morphology kn-keyword=morphology END start-ver=1.4 cd-journal=joma no-vol=2026 cd-vols= no-issue=1 article-no= start-page=1926696 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phenotypic Characterization of Porphyromonas gulae Fimbria Mutants en-subtitle= kn-subtitle= en-abstract= kn-abstract=Porphyromonas gulae has been established as a pathogen in animal periodontal disease and expresses several virulence factors, including fimbriae, lipopolysaccharide, and proteases. P. gulae fimbriae are classified into three genotypes (A, B, and C) based on the fimbrillin (fimA) gene encoding a fimbrial subunit protein. We previously reported that P. gulae organisms with type C fimbriae were clearly more virulent as compared to those with other fimbria types, though the basic function of this is not fully understood. Here, we investigated the function of fimbriae using fimA-deficient mutants. In the present study, bacterial fimbriae were related to biofilm tenacity, whereas biofilm formation was not. Also, P. gulae fimbriae are involved in bacterial adhesion and entry into gingival epithelial cells. The role of P. gulae fimbriae in bacterial pathogenicity was then determined using fimA-deficient mutants with a silkworm infection model. Additionally, P. gulae infection can induce inflammatory responses in gingival epithelial cells and also inhibit cell migration and proliferation. In contrast, a P. gulae fimA-deficient mutant did not cause several of those cellular responses. Together, the results show that fimbriae contribute to the pathogenicity of P. gulae by affecting bacterial functions and host cell interactions. en-copyright= kn-copyright= en-aut-name=InabaHiroaki en-aut-sei=Inaba en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaSho en-aut-sei=Yoshida en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NomuraRyota en-aut-sei=Nomura en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanoKazuhiko en-aut-sei=Nakano en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Matsumoto-NakanoMichiyo en-aut-sei=Matsumoto-Nakano en-aut-mei=Michiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=5 en-affil=Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka kn-affil= affil-num=6 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=biofilm kn-keyword=biofilm en-keyword=cell invasion kn-keyword=cell invasion en-keyword=cell migration kn-keyword=cell migration en-keyword=fimbriae kn-keyword=fimbriae en-keyword=periodontitis kn-keyword=periodontitis en-keyword=Porphyromonas gulae kn-keyword=Porphyromonas gulae en-keyword=silkworm larvae kn-keyword=silkworm larvae END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue= article-no= start-page=112872 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prediction of tool-path and cycle time errors of CNC machining using a transformer-based deep learning model en-subtitle= kn-subtitle= en-abstract= kn-abstract=The prediction of tool-path and cycle time errors of computer numerical control (CNC) machining is important in manufacturing field. In this study, these errors are considered as sequential data corresponding to the lines of G-code, i.e., the error prediction is a sequence-to-sequence task, and a Transformer-based deep learning model was constructed to predict the tool-path and cycle time errors simultaneously, taking the positional increments and feed rate as the input. The training datasets were created by running a randomly generated G-code on a real CNC machine tool and subsequently tracking the actual errors, where the motion and feed rate are stochastically defined. The model is validated by conducting the error prediction on six sets of G-code. In addition, the comparison with a Bi-LSTM-based deep learning model is conducted. The results show that the prediction accuracy of the Transformer model can achieve the mean prediction accuracies of ±1 μm and ±1 ms in tool-path and cycle time error predictions, respectively. Furthermore, the Transformer model has a smaller prediction uncertainty than the Bi-LSTM model. Compared with conventional methods only analyzing tool-path errors or cycle-time errors, the utilized model has an advantage in its ability to simultaneously predict tool-path errors and cycle time errors. en-copyright= kn-copyright= en-aut-name=KanekoKazuki en-aut-sei=Kaneko en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiZongze en-aut-sei=Li en-aut-mei=Zongze kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Tech, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Advanced Science and Engineering, Hiroshima University kn-affil= en-keyword=CNC machining kn-keyword=CNC machining en-keyword=Tool-path error kn-keyword=Tool-path error en-keyword=Cycle time error kn-keyword=Cycle time error en-keyword=Deep learning kn-keyword=Deep learning en-keyword=Transformer kn-keyword=Transformer END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=5 article-no= start-page=466 end-page=477 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260905 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-Time Estimation of Temperature Field and Thermal Displacement in Machine Tool Linear Motion Systems Using Servo Data en-subtitle= kn-subtitle= en-abstract= kn-abstract=Heat generated in machine tools during operation causes thermal deformation and deteriorates machining accuracy. To suppress thermal deformation and the resulting displacement, strategies such as reducing heat generation, cooling machine elements that generate heat, and compensating for thermal displacement are generally adopted. However, existing methods for estimating and compensating for thermal deformation and displacement can only be adopted in limited situations. In particular, there are few reports on real-time estimation methods that take into account moving parts and actual machine operating conditions. For high-accuracy machining, it is important to understand the temperature field and the associated displacement. In this study, real-time estimation of the temperature field and displacement is carried out on a test apparatus equipped with a ball screw drive system and a linear guideway system. In the estimation process, heat generation values are first calculated from servo data corresponding to the machine operation. Using these calculated values, the temperature field is then derived through the finite volume method. Finally, the thermal displacement is obtained from the temperature field using a simplified estimation method. The results are validated by comparison with experimental data and with results from commercial finite element method software, demonstrating the effectiveness and real-time performance of the proposed approach. en-copyright= kn-copyright= en-aut-name=KondoRyoji en-aut-sei=Kondo en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhashiKazuhito en-aut-sei=Ohashi en-aut-mei=Kazuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=YASDA PRECISION TOOLS K.K. kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=machine tool kn-keyword=machine tool en-keyword=finite volume method kn-keyword=finite volume method en-keyword=temperature field kn-keyword=temperature field en-keyword=thermal displacement kn-keyword=thermal displacement en-keyword=real-time estimation kn-keyword=real-time estimation END start-ver=1.4 cd-journal=joma no-vol=38 cd-vols= no-issue=9 article-no= start-page=e70259 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=Marine flatworms as windows into the evolution of bilaterian neuropeptide signalling en-subtitle= kn-subtitle= en-abstract= kn-abstract=The evolutionary origin(s) of neuropeptide signalling is still largely unknown. It has been hypothesised that signal transmission via neuropeptides played a crucial role in the regulation of nervous systems in the bilaterian ancestor. Identification, expression and functional analyses of neuropeptides and their receptors across different taxonomic groups are important for better understanding the origin(s) of bilaterian neuropeptide signalling. An example is flatworms belonging to the Platyhelminthes (spiralian protostomes) and Xenacoelomorpha (sister to all Bilateria or sister to Ambulacraria). Despite their simple morphology (i.e., a body plan lacking a coelom and circulatory system), they often possess brain-like central nervous systems and a number of bilaterian-conserved neuropeptides. This feature makes them useful models for analyses of neuropeptides and their links to nervous systems. Although previous studies have revealed orthologous relationships between vertebrate neuropeptides and those found in both marine Platyhelminthes and Xenacoelomorpha, our work suggests possible ancestral functions of vasopressin/oxytocin (VP/OT) peptides (platytocin) in these groups. en-copyright= kn-copyright= en-aut-name=NakamuraRyo en-aut-sei=Nakamura en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=BaillyXavier en-aut-sei=Bailly en-aut-mei=Xavier kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=SakamotoTatsuya en-aut-sei=Sakamoto en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Ushimado Marine Institute, Faculty of Science, Okayama University kn-affil= affil-num=2 en-affil=Ushimado Marine Institute, Faculty of Science, Okayama University kn-affil= affil-num=3 en-affil=Multicellular Marine Models Team, CNRS ? Sorbonne University ? Station Biologique de Roscoff kn-affil= affil-num=4 en-affil=Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Ushimado Marine Institute, Faculty of Science, Okayama University kn-affil= en-keyword=Neuropeptide kn-keyword=Neuropeptide en-keyword=Nervous system evolution kn-keyword=Nervous system evolution en-keyword=Platyhelminthes kn-keyword=Platyhelminthes en-keyword=Xenacoelomorpha kn-keyword=Xenacoelomorpha 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=12 cd-vols= no-issue=1 article-no= start-page=44 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260622 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of a preoperative accuracy prediction model using machine learning for implant placement in static-guided surgery: retrospective observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose This study aimed to develop a machine learning model capable of preoperatively predicting three-dimensional implant placement errors at the implant apex in static-guided surgery and to identify the clinical features associated with placement accuracy.
Methods Clinical data partially derived from a previous observational study were analyzed. In total, 181 patients and 480 implants placed using fully static-guided surgery were included in this study. The outcome variable was defined as three-dimensional implant placement error at the implant apex relative to the preoperative simulation, dichotomized as less than 0.5 mm or ??0.5 mm. Twenty-one clinical and radiographic factors previously suggested to influence the placement accuracy were used as explanatory variables. The feature importance was evaluated using three gradient boosting decision tree models. Furthermore, a stacking model combining multiple classifiers was constructed, and the classification performance was assessed using ten-fold cross-validation.
Results The feature importance analysis identified 12 features associated with implant placement errors. The stacking model demonstrated superior classification performance compared to individual classifiers. The true positive rate was 0.73, false negative rate was 0.27, false positive rate was 0.14, and true negative rate was 0.86.
Conclusions The proposed stacking model correctly classified 86% of cases with implant placement error less than 0.5 mm and 73% of cases with implant placement error of ??0.5 mm. These findings suggest that the proposed model may support the preoperative evaluation of implant placement accuracy in static-guided surgeries. en-copyright= kn-copyright= en-aut-name=MinoTakuya en-aut-sei=Mino en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuokaYurina en-aut-sei=Matsuoka en-aut-mei=Yurina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorookaKen’ichi en-aut-sei=Morooka en-aut-mei=Ken’ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TokumotoKana en-aut-sei=Tokumoto en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimizuHiroaki en-aut-sei=Shimizu en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurosakiYoko en-aut-sei=Kurosaki en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Kimura-OnoAya en-aut-sei=Kimura-Ono en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KishimotoHiromitsu en-aut-sei=Kishimoto en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KubokiTakuo en-aut-sei=Kuboki en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MaekawaKenji en-aut-sei=Maekawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University kn-affil= affil-num=2 en-affil=Department of Semiconductor, Computer Science and Applied Mathematics, Graduate School of Science and Technology, Kumamoto University kn-affil= affil-num=3 en-affil=Division of Biomedical Engineering, Faculty of Advanced Science and Technology, Kumamoto University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, School of Medicine, Hyogo Medical University kn-affil= affil-num=5 en-affil=Shimizu Dental Clinic kn-affil= affil-num=6 en-affil=Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University kn-affil= affil-num=7 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, School of Medicine, Hyogo Medical University kn-affil= affil-num=9 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University kn-affil= en-keyword=Implant placement kn-keyword=Implant placement en-keyword=Accuracy kn-keyword=Accuracy en-keyword=Surgical guide kn-keyword=Surgical guide en-keyword=Machine learning kn-keyword=Machine learning en-keyword=Prediction algorithms kn-keyword=Prediction algorithms en-keyword=Decision trees kn-keyword=Decision trees en-keyword=Support vector machine kn-keyword=Support vector machine en-keyword=Sensitivity and specificity kn-keyword=Sensitivity and specificity END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=17 article-no= start-page=2822 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Granular Swollen Epithelial Cells in Native Kidney Biopsies: Prevalence, Clinicopathological Associations and Kidney Outcomes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Granular swollen epithelial cells (GSECs) have been described primarily in mitochondrial cytopathies, in which they are regarded as a characteristic pathological finding that may aid in the diagnosis of mitochondrial dysfunction; however, their prevalence and clinical significance in native kidney disease remain unclear. We aimed to evaluate the prevalence, clinicopathological associations, and prognostic significance of GSECs in native kidney biopsy specimens. Methods: Among 1165 adults who underwent native kidney biopsy between 2011 and 2024, 501 patients with evaluable medullary tissue were included in this retrospective cohort study. GSECs were defined as enlarged tubular epithelial cells with conspicuous granular cytoplasm in medullary tubules, and cases were classified as GSEC-positive when at least one unequivocal GSEC was identified. Clinical and histopathological characteristics were compared between groups, and kidney outcomes were evaluated using Cox proportional hazards models. Results: The mean baseline eGFR was 60.8 ± 26.3 mL/min/1.73 m2, and the median urinary protein excretion was 1.1 g/gCr. During a median follow-up of 2.3 years, 112 patients (22.3%) reached the composite kidney outcome. GSECs were identified in 18% of native kidney biopsy specimens containing evaluable medullary tissue, and were observed across a broad spectrum of kidney diseases. GSEC positivity was associated with older age and underlying pathological diagnoses but was not associated with baseline kidney function or proteinuria. Kaplan?Meier and multivariable Cox analyses revealed no significant association between GSECs and kidney prognosis. Conclusions: GSECs are not specific to kidney allografts and are observed in a subset of diverse native kidney diseases. Although associated with certain clinical characteristics, no independent association between GSECs and kidney outcomes was observed in this cohort. These findings suggest that GSECs may reflect disease-dependent biological responses to tubular epithelial stress, potentially related to metabolic or mitochondrial alterations, rather than a marker of progressive kidney injury. en-copyright= kn-copyright= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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= en-keyword=granular swollen epithelial cells kn-keyword=granular swollen epithelial cells en-keyword=native kidney biopsy kn-keyword=native kidney biopsy en-keyword=kidney outcomes kn-keyword=kidney outcomes en-keyword=renal medulla kn-keyword=renal medulla en-keyword=mitochondria kn-keyword=mitochondria END start-ver=1.4 cd-journal=joma no-vol=112 cd-vols= no-issue= article-no= start-page=102428 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=Adaptive oligodendrogenesis regulates blood-hypothalamus barrier permeability, hypothalamic glucose sensing and systemic glucose homeostasis in male mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Brain glucose sensing is critical for survival during hypoglycaemia, yet how glucose-sensing neurons access circulating glucose concentrations to maintain glucose homeostasis remains poorly understood. Here we tested the hypothesis that adult oligodendrogenesis in the median eminence (ME) is responsive to changes in blood glucose levels and contributes to hypothalamic glucose sensing through regulation of the blood-hypothalamus barrier.
Methods: We used glycemic challenges and hypoinsulinaemic clamp studies to identify the effect of systemic changes in glycaemia on hypothalamic oligodendrocyte lineage cells. We used conditional knockout mouse models to dissect the respective contributions of adult oligodendrogenesis and new myelin formation to glucose homeostasis in adult male mice. Analyses combined immunofluorescence, serial electron microscopy, whole-brain tissue clearing, and transcriptomic analyses.
Results: We found that adult oligodendrogenesis in the median eminence (ME) is modulated by changes in circulating glucose levels and rapidly upregulated by hypoglycaemia. Genetic blockade of new oligodendrocyte production in adult male mice impairs the regulation of glucose homeostasis, the integrity of the ME blood-hypothalamus barrier, and hypothalamic glucose sensing. Unexpectedly, functional integrity of adult-formed myelin is not required for the maintenance of glucose homeostasis. Instead, we show that blockade of adult oligodendrogenesis disrupts hypothalamic expression of A disintegrin and metallopeptidase with thrombospondin motifs 4 (ADAMTS4), a metallopeptidase whose brain expression is restricted to the oligodendrocyte lineage and whose ME expression requires ongoing adult oligodendrogenesis. We show that ADAMTS4 regulates hypothalamic perineuronal net deposition, vascular permeability and glucose sensing. Finally, we show that ME ADAMTS4 expression is regulated by changes in peripheral glycaemia and is dysregulated in diabetes, providing a mechanism by which ME oligodendrocytes contribute to the regulation of glucose homeostasis. en-copyright= kn-copyright= en-aut-name=BullerSophie en-aut-sei=Buller en-aut-mei=Sophie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=StaricoffEmily O. en-aut-sei=Staricoff en-aut-mei=Emily O. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RichesChristine en-aut-sei=Riches en-aut-mei=Christine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsangAnthony en-aut-sei=Tsang en-aut-mei=Anthony kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GiavaraGiada en-aut-sei=Giavara en-aut-mei=Giada kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JosipovicMasa en-aut-sei=Josipovic en-aut-mei=Masa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkemuraKentaro en-aut-sei=Ikemura en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OpokuGabriel en-aut-sei=Opoku en-aut-mei=Gabriel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 ORCID= en-aut-name=StenzelSaskia en-aut-sei=Stenzel en-aut-mei=Saskia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NayarStuart G. en-aut-sei=Nayar en-aut-mei=Stuart G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Ramos VegaMarta en-aut-sei=Ramos Vega en-aut-mei=Marta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Hecksher-S?rensenJacob en-aut-sei=Hecksher-S?rensen en-aut-mei=Jacob kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TimmlerSebastian en-aut-sei=Timmler en-aut-mei=Sebastian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=DowsettGeorgina K.C. en-aut-sei=Dowsett en-aut-mei=Georgina K.C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=LamBrian Y.H. en-aut-sei=Lam en-aut-mei=Brian Y.H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YeoGiles S.H. en-aut-sei=Yeo en-aut-mei=Giles S.H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=AlongeKimberly M. en-aut-sei=Alonge en-aut-mei=Kimberly M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=LiHuiliang en-aut-sei=Li en-aut-mei=Huiliang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=RichardsonWilliam D. en-aut-sei=Richardson en-aut-mei=William D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=EvansMark L. en-aut-sei=Evans en-aut-mei=Mark L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=BlouetClemence en-aut-sei=Blouet en-aut-mei=Clemence kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge kn-affil= affil-num=2 en-affil=Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge kn-affil= affil-num=3 en-affil=Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge kn-affil= affil-num=4 en-affil=Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge kn-affil= affil-num=5 en-affil=Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge kn-affil= affil-num=6 en-affil=Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge 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=Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge kn-affil= affil-num=12 en-affil=Wolfson Institute for Biomedical Research, University College London kn-affil= affil-num=13 en-affil=GUBRA kn-affil= affil-num=14 en-affil=GUBRA kn-affil= affil-num=15 en-affil=Cambridge Stem Cell Institute, University of Cambridge kn-affil= affil-num=16 en-affil=Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge kn-affil= affil-num=17 en-affil=Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge kn-affil= affil-num=18 en-affil=Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge kn-affil= affil-num=19 en-affil=Diabetes Institute, University of Washington kn-affil= affil-num=20 en-affil=Wolfson Institute for Biomedical Research, University College London kn-affil= affil-num=21 en-affil=Wolfson Institute for Biomedical Research, University College London kn-affil= affil-num=22 en-affil=Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge kn-affil= affil-num=23 en-affil=Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge kn-affil= en-keyword=Oligodendrogenesis kn-keyword=Oligodendrogenesis en-keyword=Median eminence kn-keyword=Median eminence en-keyword=Blood-hypothalamus barrier kn-keyword=Blood-hypothalamus barrier en-keyword=ADAMTS4 kn-keyword=ADAMTS4 en-keyword=Glucose sensing kn-keyword=Glucose sensing en-keyword=Hypoglycaemia kn-keyword=Hypoglycaemia 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=31 cd-vols= no-issue=9 article-no= start-page=1890 end-page=1900 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260616 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Event-free survival and recurrence patterns after curative resection for locally advanced head and neck squamous cell carcinoma: single-institution real-world outcomes prior to the introduction of perioperative immunotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Perioperative immune checkpoint inhibitors have improved outcomes for resectable locally advanced head and neck squamous cell carcinoma (HNSCC). However, real-world surgical outcome data based on contemporary endpoints remain limited.
Methods We retrospectively analyzed 233 patients who underwent curative-intent surgery for locally advanced HNSCC. Event-free survival (EFS) and overall survival (OS) were evaluated. Unresectable recurrence-free survival (URFS) was explored as an additional endpoint to capture post-recurrence treatment feasibility. Prognostic factors were assessed using Cox proportional hazards models.
Results The median follow-up duration was 18.2 months. The 1-year EFS and OS rates were 67.1% and 89.4%, respectively. pN2 or higher disease, venous invasion, and perineural invasion were identified as independent adverse prognostic factors. Recurrence occurred in 34.8% of patients; among these, disease control at the last follow-up was achieved in 61.7% following curative-intent salvage treatment. Salvage surgery was associated with significantly improved post-recurrence survival (p? Conclusions This study provides real-world surgical outcome data for resectable locally advanced HNSCC prior to the introduction of perioperative immunotherapy. Recurrence remains a major clinical challenge, with heterogeneous post-recurrence outcomes influenced by treatment feasibility. These findings may help inform interpretation of treatment outcomes and clinical decision-making in the evolving era of perioperative immunotherapy. en-copyright= kn-copyright= en-aut-name=MakinoTakuma en-aut-sei=Makino en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaoiYuto en-aut-sei=Naoi en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasegawaGo en-aut-sei=Hasegawa en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamasakiTakuto en-aut-sei=Yamasaki en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NodaHiroki en-aut-sei=Noda en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimotoShohei en-aut-sei=Fujimoto en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoJunya en-aut-sei=Matsumoto en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Head and neck squamous cell carcinoma kn-keyword=Head and neck squamous cell carcinoma en-keyword=Surgery kn-keyword=Surgery en-keyword=Event-free survival kn-keyword=Event-free survival en-keyword=Recurrence kn-keyword=Recurrence en-keyword=Salvage surgery kn-keyword=Salvage surgery END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=2 article-no= start-page=e70089 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Species‐specific roles of cellular communication network proteins in cartilage development: A comparative study using in vitro chondrogenic models en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cellular communication network (CCN) proteins are key matricellular regulators of cartilage development, yet their species-specific roles and network-level context remain unclear. This study integrated bulk RNA sequencing from chicken and mouse embryonic limb bud micromass cultures and human mesenchymal stem cell chondrogenesis with co-expression, protein?protein interaction, and ortholog analyses to construct CCN-centered regulatory networks across models. CCN1 and CCN2 emerged as dominant, conserved hubs enriched in collagen-containing extracellular matrix, cartilage development, and growth factor signaling modules, whereas CCN3?CCN6 showed lower context-dependent expression and connectivity. Functional and ortholog analyses revealed moderate pathway conservation, with high conservation of IGF, EGFR, and HIF-1 signaling, but reduced overlap in hypoxia and mechanosensing/Hippo categories, indicating species-specific tuning of environmental sensing. A focused ortholog screen identified multifunctional conserved hubs, including COL2A1, TGFBR1, SMAD3, RUNX2, HIF1A, IGF1, SPP1, and CD44. Single-cell RNA-seq meta-analysis of human iPSC-derived chondrogenesis and embryonic limb datasets showed CCN1/2 expression and homologous network activity peaking in mesenchymal and early chondrocyte populations, consistent with model-dependent persistence into hypertrophic and ossification stages in vivo. Overall, this work defines a conserved CCN1/2-centered axis integrating extracellular matrix formation with growth factor and mechanical cues, providing a framework for model selection and CCN-targeted cartilage regeneration strategies. en-copyright= kn-copyright= en-aut-name=WangZhangzheng en-aut-sei=Wang en-aut-mei=Zhangzheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=V?g?Judit en-aut-sei=V?g? en-aut-mei=Judit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Tak?csRoland en-aut-sei=Tak?cs en-aut-mei=Roland kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=P?liskaSzil?rd en-aut-sei=P?liska en-aut-mei=Szil?rd kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimEe Hyun en-aut-sei=Kim en-aut-mei=Ee Hyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JinEun‐Jung en-aut-sei=Jin en-aut-mei=Eun‐Jung kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KleerCelina G en-aut-sei=Kleer en-aut-mei=Celina G kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=PerbalBernard en-aut-sei=Perbal en-aut-mei=Bernard kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MattaCsaba en-aut-sei=Matta en-aut-mei=Csaba kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen kn-affil= affil-num=2 en-affil=Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen kn-affil= affil-num=3 en-affil=Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen kn-affil= affil-num=4 en-affil=Genomic Medicine and Bioinformatics Core Facility Department of Biochemistry and Molecular Biology Faculty of Medicine, University of Debrecen kn-affil= affil-num=5 en-affil=Department of Biomedical Materials Science Graduate School of JABA, Wonkwang University kn-affil= affil-num=6 en-affil=Department of Biomedical Materials Science Graduate School of JABA, Wonkwang University kn-affil= affil-num=7 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University, Faculty of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Department of Pathology, University of Michigan Medical School kn-affil= affil-num=9 en-affil=International CCN Society kn-affil= affil-num=10 en-affil=Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen kn-affil= en-keyword=cartilage regeneration kn-keyword=cartilage regeneration en-keyword=CCN kn-keyword=CCN en-keyword=chondrogenesis kn-keyword=chondrogenesis en-keyword=osteoarthritis kn-keyword=osteoarthritis en-keyword=regulatory network kn-keyword=regulatory network en-keyword=transcriptomics kn-keyword=transcriptomics END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=9 article-no= start-page=e0086926 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260901 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Combinations of long terminal repeat and tax protein substitutions influence bovine leukemia virus transmission through altered viral productivity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bovine leukemia virus (BLV) infection imposes a substantial economic burden on the global cattle industry. Although proviral load (PVL) in blood influences transmission, the effects of viral genetic variations, including the high viral production-associated long terminal repeat (LTR) substitution at nucleotide position 175 (LTR175), on herd-level dynamics remain unclear. This study investigated the effects of specific substitutions on the regulation of viral productivity and transmission. Longitudinal monitoring of a single farm (herd size: 50?68 cows; 438 samples collected) over a 7-year period revealed that viral strains carrying cytosine at LTR175 (LTR175C) significantly increased in frequency, becoming dominant over wild-type strains carrying thymidine. In contrast, amino acid substitutions in the Tax protein at positions 69 (Tax69) and 73 (Tax73) modified viral transactivation independent of LTR175. Structural modeling via AlphaFold2 predicted that Tax69 and Tax73 mutations alter protein properties, suggesting modulation of transactivation activity. Consistent with this prediction, in vitro assays confirmed that the substitutions modified viral production by regulating transactivation independent of LTR175. Moreover, high viral-productivity haplotypes containing LTR175C and Tax73Q (glutamine at amino acid residue 73) exhibited a transmission advantage within the herd, even when host PVL levels were not significantly elevated. These findings suggest that cellular-level viral productivity is one of the key determinants of transmission fitness. Overall, this study revealed a regulatory interaction between the LTR and Tax protein that optimizes viral spread and highlights the need for control strategies that account for viral genetic substitutions. en-copyright= kn-copyright= en-aut-name=MurakamiHironobu en-aut-sei=Murakami en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoReiichiro en-aut-sei=Sato en-aut-mei=Reiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SogawaKazuyuki en-aut-sei=Sogawa en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshidaHiroho en-aut-sei=Ishida en-aut-mei=Hiroho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagaiMakoto en-aut-sei=Nagai en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=School of Veterinary Medicine, Azabu University kn-affil= affil-num=2 en-affil=Graduate School of Medicine and Veterinary Medicine, University of Miyazaki kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=School of Life and EnvironmentaScience, Azabu University kn-affil= affil-num=5 en-affil=School of Veterinary Medicine, Azabu University kn-affil= affil-num=6 en-affil=School of Veterinary Medicine, Azabu University kn-affil= en-keyword=bovine leukemia virus kn-keyword=bovine leukemia virus en-keyword=substitution kn-keyword=substitution en-keyword=transmission kn-keyword=transmission en-keyword=haplotype kn-keyword=haplotype en-keyword=molecular clone kn-keyword=molecular clone en-keyword=proviral load kn-keyword=proviral load en-keyword=reverse genetics kn-keyword=reverse genetics END start-ver=1.4 cd-journal=joma no-vol=139 cd-vols= no-issue=2 article-no= start-page=255 end-page=265 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=Knockout of a single aquaporin, OsPIP2;4, decreases root water permeability in rice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aquaporins (AQPs) are membrane proteins that facilitate water transport and are present in nearly all bacterial, animal, and plant cells. In plants, AQPs are classified into four or more subfamilies, with plasma membrane intrinsic proteins (PIPs) playing a key role in root water uptake and cellular water regulation. Previous studies have demonstrated that PIPs contribute to root hydraulic conductivity (Lpr) in various plant species. In this study, we examined the specific role of OsPIP2;4, one of the PIP-type aquaporins among 11 rice (Oryza sativa) PIP2s, in regulating Lpr. Transgenic rice plants, including OsPIP2;4-knockout (KO) and overexpressing (Ox) lines, were used for this investigation. Two independent KO lines, generated via the CRISPR-Cas9 system and T-DNA insertion mutagenesis, respectively, showed significantly lower Lpr compared to wild-type rice plants. The decrease in Lpr in the T-DNA KO line was associated with reduced OsPIP2;4 transcript levels, measured by real-time PCR, and lower OsPIP2;4 protein levels, as shown by immunohistochemical analysis. Conversely, no notable increase in Lpr was observed in the Ox lines. These results suggest that OsPIP2;4 is expressed in appropriate tissues in rice roots and is a key factor influencing Lpr. This research represents a significant step toward further understanding the physiological functions of OsPIP2;4 in rice. en-copyright= kn-copyright= en-aut-name=OnishiAya en-aut-sei=Onishi en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=IshitsukaRyo en-aut-sei=Ishitsuka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasanoShizuka en-aut-sei=Sasano en-aut-mei=Shizuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=MitoYunosuke en-aut-sei=Mito en-aut-mei=Yunosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UtsugiShigeko en-aut-sei=Utsugi en-aut-mei=Shigeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshikawaJunko en-aut-sei=Ishikawa en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MahdiehMajid en-aut-sei=Mahdieh en-aut-mei=Majid kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu 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=Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University kn-affil= affil-num=6 en-affil=Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University kn-affil= affil-num=7 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=8 en-affil=Institute of Crop Science, NARO kn-affil= affil-num=9 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=10 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=PIP aquaporin kn-keyword=PIP aquaporin en-keyword=Rice kn-keyword=Rice en-keyword=Root hydraulic conductivity kn-keyword=Root hydraulic conductivity en-keyword=Root pressure chamber kn-keyword=Root pressure chamber END start-ver=1.4 cd-journal=joma no-vol=146 cd-vols= no-issue=9 article-no= start-page=864 end-page=876 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260901 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Optimization of Smart Grid Operation Considering Diverse Electricity Consumption Patterns kn-title=多様な電力消費形態を考慮したスマートグリッド運用の最適化 en-subtitle= kn-subtitle= en-abstract= kn-abstract=　This study examines an optimal operation model for a smart grid composed of multiple microgrids to promote renewable energy use in Japan. In Japan, about 70% of electricity is still supplied by fossil fuel power, while renewables account for only 18% despite a 36?38% target for 2030. Using demand and photovoltaic data from Setagaya Ward, we construct a system model with factory/office and residential microgrids and formulate a mathematical optimization model that considers power interchange, batteries and heat storage. Numerical experiments based on several case studies show the effectiveness of smart grid operation designed according to the proposed model in promoting renewable energy utilization and reducing total generation cost. In particular, the results show that increasing photovoltaic capacity, increasing the number of microgrids, and considering heat demand are all effective measures. However, these benefits depend on the season. Future work should extend the system model to account for seasonal variability and associated investment costs. en-copyright= kn-copyright= en-aut-name=KawamotoTakaki en-aut-sei=Kawamoto en-aut-mei=Takaki kn-aut-name=川本卓樹 kn-aut-sei=川本 kn-aut-mei=卓樹 aut-affil-num=1 ORCID= en-aut-name=TodaYuriko en-aut-sei=Toda en-aut-mei=Yuriko kn-aut-name=戸田悠莉子 kn-aut-sei=戸田 kn-aut-mei=悠莉子 aut-affil-num=2 ORCID= en-aut-name=HasuikeTakashi en-aut-sei=Hasuike en-aut-mei=Takashi kn-aut-name=蓮池隆 kn-aut-sei=蓮池 kn-aut-mei=隆 aut-affil-num=3 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil=岡山大学学術研究院環境生命自然科学学域 affil-num=2 en-affil=School of Creative Science and Engineering, Waseda University kn-affil=早稲田大学大学院創造理工学研究科 affil-num=3 en-affil=School of Creative Science and Engineering, Waseda University kn-affil=早稲田大学大学院創造理工学研究科 en-keyword=スマートグリッド (smart grid) kn-keyword=スマートグリッド (smart grid) en-keyword=マイクログリッド (microgrid) kn-keyword=マイクログリッド (microgrid) en-keyword=再生可能エネルギー (renewable energy) kn-keyword=再生可能エネルギー (renewable energy) en-keyword=電力融通 (power interchange) kn-keyword=電力融通 (power interchange) END start-ver=1.4 cd-journal=joma no-vol=192 cd-vols= no-issue= article-no= start-page=37 end-page=51 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=A Practical Study on Collaborative Training of Novice University Note-takers for Support University Students Who Are Deaf or Hard of Hearing: Examining a Training Model Utilizing Diverse Human Resources kn-title=聴覚障害学生支援のための初学者向け大学ノートテイカー共同養成研修の効果・課題・あり方 ―多様な人的リソースを活用した養成研修モデルの検討― en-subtitle= kn-subtitle= en-abstract= kn-abstract=　本研究は，多様な人的リソースを活用した聴覚障害学生支援のための初学者向けノートテイカー共同養成研修の効果と課題を明らかにし，今後の共同養成研修のあり方について検討することを目的とした。共同養成研修の効果として，【他大学との交流の有効性】，【研修順序の有効性】，【研修内容の充実】などが見られ，今後の研修の生かし方として，【研鑽や活動拡大】，【支援・研修の充実】などが挙げられており，研修の有効性が明らかになった。一方で，共同養成研修の課題として，交流プログラムの満足度が相対的に最も低く，【時間不足】が背景にあると考えられた。これらのことを踏まえて，共同養成研修のあり方として，学生・教職員が交流する十分な時間の確保や，各講義時間の増加のために，動画を視聴するオンデマンド形式を基本として，交流や演習などを対面，またはリアルタイムオンラインで実施するなどの研修方法が考えられる。 en-copyright= kn-copyright= en-aut-name=SHIMONAKAMURATakeshi en-aut-sei=SHIMONAKAMURA en-aut-mei=Takeshi kn-aut-name=下中村武 kn-aut-sei=下中村 kn-aut-mei=武 aut-affil-num=1 ORCID= en-aut-name=INOUEHiroko en-aut-sei=INOUE en-aut-mei=Hiroko kn-aut-name=井上寛子 kn-aut-sei=井上 kn-aut-mei=寛子 aut-affil-num=2 ORCID= en-aut-name=TAKAGIYuka en-aut-sei=TAKAGI en-aut-mei=Yuka kn-aut-name=木由香 kn-aut-sei=木 kn-aut-mei=由香 aut-affil-num=3 ORCID= en-aut-name=SOEJIMAHirofumi en-aut-sei=SOEJIMA en-aut-mei=Hirofumi kn-aut-name=副島弘文 kn-aut-sei=副島 kn-aut-mei=弘文 aut-affil-num=4 ORCID= en-aut-name=FUJISENoboru en-aut-sei=FUJISE en-aut-mei=Noboru kn-aut-name=藤瀬昇 kn-aut-sei=藤瀬 kn-aut-mei=昇 aut-affil-num=5 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=Child Consultation Center, Kumamoto city kn-affil=熊本市児童相談所 affil-num=3 en-affil=Student Accessibility Support Room, Kumamoto University kn-affil=熊本大学障がい学生支援室 affil-num=4 en-affil=Student Accessibility Support Room, Kumamoto University kn-affil=熊本大学障がい学生支援室 affil-num=5 en-affil=Kumamoto Prefecture Mental Health Welfare Center kn-affil=熊本県精神保健福祉センター en-keyword=聴覚障害 kn-keyword=聴覚障害 en-keyword=障害学生 kn-keyword=障害学生 en-keyword=情報保障 kn-keyword=情報保障 en-keyword=ノートテイク kn-keyword=ノートテイク en-keyword=共同養成 kn-keyword=共同養成 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=27 cd-vols= no-issue=17 article-no= start-page=7542 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260823 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Assessment of the Association of Periodontitis and Diabetes Mellitus with Alzheimer’s Disease in a Mouse Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=The purpose of the present study was to investigate how periodontitis and diabetes mellitus (DM) are associated with Alzheimer’s disease (AD) through microRNA (miRNA) using AD model mice. The experimental period was 8 weeks. Twenty-four male knock-in mice (B6-AppNL-G-F/NL-G-F/J) were divided into four groups: control group fed a normal diet (C), DM group fed a high-fat/sucrose diet (DM), periodontitis (P) group, and DM + periodontitis (DM+P) group. Memory performance was compared using the Y-maze test. Next-generation sequencing was performed on brain samples, and fold changes in miRNA expression were calculated by comparing the DM+P and C groups. Integrated miRNA?mRNA analysis identified putative miRNA-targeted mRNAs, and protein expression of the top candidate gene was assessed. Memory function in the DM+P group was significantly lower than in the C group. Among the seven mRNAs identified by the integrated analysis, Neurod1 showed the greatest decrease in expression, and it was predicted to be regulated by miR-693-3p. Neurod1 protein expression in the hippocampus was significantly lower in the DM+P group than the C group. Our results suggest that the combined exposure to periodontitis and DM was associated with AD-like pathological changes and identified the miR-693-3p/Neurod1 pair as a candidate regulatory axis. en-copyright= kn-copyright= en-aut-name=NakaharaMomoko en-aut-sei=Nakahara en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KataokaKota en-aut-sei=Kataoka en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaruyamaTakayuki en-aut-sei=Maruyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NurhamimMohammad en-aut-sei=Nurhamim en-aut-mei=Mohammad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhangYixuan en-aut-sei=Zhang en-aut-mei=Yixuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuharaDaiki en-aut-sei=Fukuhara en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Uchida-FukuharaYoko en-aut-sei=Uchida-Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IslamMd Monirul en-aut-sei=Islam en-aut-mei=Md Monirul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SaitoTakashi en-aut-sei=Saito en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Division of Dentistry, Medical Development Field, Okayama University kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Dental School, Okayama University kn-affil= affil-num=7 en-affil=Laboratory of Biological Anthropology, Research Center for Integrative Evolutionary Science, The Graduate University for Advanced Studies, SOKENDAI kn-affil= affil-num=8 en-affil=Centre for Policy Studies, University College Cork kn-affil= affil-num=9 en-affil=Department of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health Care kn-affil= affil-num=10 en-affil=Department of Neuropathology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=11 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Alzheimer’s disease kn-keyword=Alzheimer’s disease en-keyword=periodontitis kn-keyword=periodontitis en-keyword=diabetes mellitus kn-keyword=diabetes mellitus en-keyword=microRNA kn-keyword=microRNA en-keyword=mRNA kn-keyword=mRNA END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fenestration Re-creation for Early Fontan Deterioration: Long-Term Hemodynamic and Clinical Outcomes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spontaneous closure of a Fontan fenestration may precipitate early hemodynamic deterioration in vulnerable patients. In such situations, fenestration re-creation may be considered as a rescue strategy when medical therapy is insufficient. However, the long-term hemodynamic consequences of this intervention remain poorly defined. We retrospectively reviewed 62 patients who underwent the Fontan procedure between January 2011 and December 2020 and subsequently experienced spontaneous fenestration closure. Patients were divided into two groups according to management strategy: those who underwent fenestration re-creation (Group 1, n?=?19) and those managed without re-creation (Group 2, n?=?43). Longitudinal hemodynamic data were analyzed using linear mixed models over a median follow-up of 10.2 years. Fenestration closed spontaneously at a median of 12 days (IQR 2.5?26.5) and initial re-creation was performed at the median of 42 days (IQR 11?213) postoperatively. Early and mide-term hemodynamic trends were broadly similar between groups, however, clear divergence emerged in the late follow-up. fenestration re-created patients demonstrated persistently higher central venous pressure and pulmonary vascular resistance, lower systemic vascular resistance, progressive increases in cardiac index, and declining oxygen saturation. Survival in this group remained above 80% during the mid-term follow-up but declined substantially in the late phase compared with patients without re-creation (52% vs. 85%, p?=?0.043). This was accompanied by higher incidences of protein-losing enteropathy/plastic bronchitis, thromboembolism, and severe cyanosis. Fenestration re-creation may provide temporary hemodynamic stabilization in early Fontan deterioration; however, its benefits appear to diminish in the late phase. These findings highlight the need for hemodynamically tailored management strategies and alternative therapeutic options for patients with deteriorating Fontan circulation. en-copyright= kn-copyright= en-aut-name=TranThi Hai Yen en-aut-sei=Tran en-aut-mei=Thi Hai Yen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuritaYoshihiko en-aut-sei=Kurita en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoMaiko en-aut-sei=Kondo en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukushimaYosuke en-aut-sei=Fukushima en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShigemitsuYusuke en-aut-sei=Shigemitsu en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawamotoYuya en-aut-sei=Kawamoto en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaraMayuko en-aut-sei=Hara en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwasakiTatsuo en-aut-sei=Iwasaki en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KasaharaShingo en-aut-sei=Kasahara en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=BabaKenji en-aut-sei=Baba en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Pediatrics, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatric anesthesiology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Cardiovascular Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Fontan operation kn-keyword=Fontan operation en-keyword=Spontaneous fenestration closure kn-keyword=Spontaneous fenestration closure en-keyword=Fenestration recreation kn-keyword=Fenestration recreation en-keyword=Longitudinal hemodynamic changes kn-keyword=Longitudinal hemodynamic changes END start-ver=1.4 cd-journal=joma no-vol=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=19 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260403 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Potential effects of intradialytic exercise therapy on physical performance in hemodialysis patients based on the intervention period: a systematic review and meta-analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Intradialytic exercise during hemodialysis (HD) improves physical function and shows high adherence. In Japan, the 2018 guideline by the Japanese Society of Renal Rehabilitation supports intradialytic exercise, but medical insurance only covers the first 90 days. As new studies have emerged since the guideline was published, we conducted a systematic review and meta-analysis to evaluate the impact and optimal duration of exercise interventions beyond 12 weeks.
Methods We followed a preregistered protocol (PROSPERO CRD42025642273) and PRISMA-P guidelines. Randomized controlled trials of adult patients undergoing HD performing structured exercise were identified via MEDLINE database (PubMed, March 2017?November 2024) and ICHUSHI-Web database. Two independent reviewers screened studies, extracted data, and assessed risk of bias using Cochrane RoB 2.0. Outcomes included peak oxygen uptake (VO2peak), maximal oxygen uptake (VO2max), 6 min walk distance, timed up and go (TUG) test, handgrip strength, sit-to-stand (STS) performance, and biochemical measures (hemoglobin, standard weekly urea Kt/V [std Kt/V]). Pooled mean differences (MD) with 95% confidence intervals (CI) were calculated using a mixed-effects model (Hartung?Knapp?Sidik?Jonkman method).
Results A total of 71 studies, including 43 newly identified studies, were included. Risk of bias was moderate-to-high. Interventions?>?12 weeks significantly improved 6 min walking distance (MD 52.4 m [95% CI 35.4?69.3], p??12 weeks of exercise.
Conclusions Our findings suggest that exercise interventions lasting more than 12 weeks can enhance physical performance. Nevertheless, the applicability of these results to older patients remains uncertain, as most evidence is derived from middle-aged cohorts.
Trial registration Registered in the PROSPERO database (CRD42025642273). en-copyright= kn-copyright= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HondaYu en-aut-sei=Honda en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KojimaShigeki en-aut-sei=Kojima en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakeHiromasa en-aut-sei=Miyake en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimotoMasatoshi en-aut-sei=Nishimoto en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HishikawaAkihito en-aut-sei=Hishikawa en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TonomuraShun en-aut-sei=Tonomura en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SofueTadashi en-aut-sei=Sofue en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiNaohiko en-aut-sei=Fujii en-aut-mei=Naohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SaitohMasakazu en-aut-sei=Saitoh en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NaritaIchiei en-aut-sei=Narita en-aut-mei=Ichiei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamagataKunihiro en-aut-sei=Yamagata en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HoshinoJunichi en-aut-sei=Hoshino en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawarazakiHiroo en-aut-sei=Kawarazaki en-aut-mei=Hiroo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SakuradaTsutomu en-aut-sei=Sakurada en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Internal Medicine, Teikyo University Hospital Mizonokuchi kn-affil= affil-num=2 en-affil=Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine kn-affil= affil-num=3 en-affil=Kojima Kidney and Dialysis Clinic kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Nara Medical University kn-affil= affil-num=6 en-affil=Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine kn-affil= affil-num=8 en-affil=Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Department of Nephrology, Hyogo Prefectural Nishinomiya Hospital kn-affil= affil-num=10 en-affil=Department of Physical Therapy, Faculty of Health Science, Juntendo University kn-affil= affil-num=11 en-affil=Niigata Institute for Health and Sports Medicine, Niigata Sports Association kn-affil= affil-num=12 en-affil=Department of Nephrology, Institute of Medicine, University of Tsukuba kn-affil= affil-num=13 en-affil=Division of Preventive and Sports Nephrology, Graduate School of Comprehensive Human Sciences, Tokyo Women’s Medical University kn-affil= affil-num=14 en-affil=Department of Internal Medicine, Teikyo University Hospital Mizonokuchi kn-affil= affil-num=15 en-affil=Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine kn-affil= en-keyword=Intradialytic exercise kn-keyword=Intradialytic exercise en-keyword=Physical performance kn-keyword=Physical performance en-keyword=Exercise period kn-keyword=Exercise period en-keyword=Short physical performance battery kn-keyword=Short physical performance battery en-keyword=Handgrip strength kn-keyword=Handgrip strength en-keyword=Systematic review kn-keyword=Systematic review en-keyword=Meta-analysis kn-keyword=Meta-analysis END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=13 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260308 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Duration-stratified effects of exercise therapy on health-related quality of life in hemodialysis patients: a systematic review and meta-analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Patients on maintenance hemodialysis (HD) have reduced health-related quality of life (HRQoL). Structured exercise therapy is recommended, but domain-specific effects and the influence of intervention duration remain uncertain. This study evaluated the impact of structured exercise therapy on multiple HRQoL domains, including fatigue and depression, stratified by intervention duration.
Methods: We conducted a systematic review and meta-analysis, searching MEDLINE (PubMed) through November 2024. The protocol was registered in PROSPERO (CRD42025642273). We included trials comparing structured exercise with non-exercise controls in adult HD patients. Primary outcomes were Short Form (SF)-36 Physical and Mental Component Summaries (PCS, MCS), fatigue, pain, general health, and depression (Beck Depression Inventory). Data were synthesized using random-effects models, stratified by intervention duration (??3 versus?>?3 months). Risk of bias was assessed using the Cochrane RoB 2 tool.
Results: We identified 94 randomized controlled trials (5228 participants); 22 reported HRQoL outcomes and were meta-analyzed. Exercise significantly improved fatigue (mean difference [MD]?+?7.27, 95% confidence interval [CI] 4.75?9.80) and reduced depressive symptoms in?>?3-month trials (MD??7.62, 95% CI??8.34 to??6.90); no???3-month depression data were available. In overall analyses, general health (MD?+?11.59, 95% CI 6.98?16.21) and PCS (MD?+?5.83, 95% CI 0.71?10.94) improved, whereas MCS (MD?+?7.60, 95% CI??3.75 to 18.94) and pain (MD?+?2.19, 95% CI??4.41 to 8.79) showed no clear benefit. Short-term interventions (??3 months) yielded significant improvements in pain and general health. In longer-term interventions (>?3 months), general health estimates were similar in magnitude but statistically nonsignificant, and pain effects were also nonsignificant with substantial heterogeneity. Fatigue improved in both duration strata.
Conclusions: Structured exercise therapy appears to improve fatigue in patients on maintenance HD and may provide additional gains in PCS and general health with interventions longer than 3 months. Improvements in depressive symptoms were observed from limited evidence, and duration-specific effects remain uncertain because no trials assessed depression at???3 months. Effects on pain and MCS remain uncertain owing to substantial heterogeneity. Larger long-term trials are needed to clarify the sustainability of HRQoL benefits beyond 3 months. en-copyright= kn-copyright= en-aut-name=HondaYu en-aut-sei=Honda en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KojimaShigeki en-aut-sei=Kojima en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakeHiromasa en-aut-sei=Miyake en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimotoMasatoshi en-aut-sei=Nishimoto en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HishikawaAkihito en-aut-sei=Hishikawa en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TonomuraShun en-aut-sei=Tonomura en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SofueTadashi en-aut-sei=Sofue en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiNaohiko en-aut-sei=Fujii en-aut-mei=Naohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SaitohMasakazu en-aut-sei=Saitoh en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NaritaIchiei en-aut-sei=Narita en-aut-mei=Ichiei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamagataKunihiro en-aut-sei=Yamagata en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HoshinoJunichi en-aut-sei=Hoshino en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawarazakiHiroo en-aut-sei=Kawarazaki en-aut-mei=Hiroo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SakuradaTsutomu en-aut-sei=Sakurada en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Teikyo University Hospital Mizonokuchi kn-affil= affil-num=3 en-affil=Kojima Kidney and Dialysis Clinic kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Nara Medical University kn-affil= affil-num=6 en-affil=Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine kn-affil= affil-num=8 en-affil=Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Department of Nephrology, Hyogo Prefectural Nishinomiya Hospital kn-affil= affil-num=10 en-affil=Department of Physical Therapy, Faculty of Health Science, Juntendo University kn-affil= affil-num=11 en-affil=Niigata Institute for Health and Sports Medicine, Niigata Sports Association kn-affil= affil-num=12 en-affil=Department of Nephrology, Institute of Medicine, University of Tsukuba kn-affil= affil-num=13 en-affil=Department of Nephrology, Tokyo Women’s Medical University kn-affil= affil-num=14 en-affil=Department of Internal Medicine, Teikyo University Hospital Mizonokuchi kn-affil= affil-num=15 en-affil=Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine kn-affil= en-keyword=Hemodialysis kn-keyword=Hemodialysis en-keyword=Exercise therapy kn-keyword=Exercise therapy en-keyword=Intradialytic exercise kn-keyword=Intradialytic exercise en-keyword=Health-related quality of life kn-keyword=Health-related quality of life en-keyword=Fatigue kn-keyword=Fatigue en-keyword=Depression kn-keyword=Depression en-keyword=Randomized controlled trials kn-keyword=Randomized controlled trials en-keyword=Meta-analysis kn-keyword=Meta-analysis END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=2 article-no= start-page=527 end-page=535 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260516 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Microcontroller-Integrated Multichannel Time Detector for Paper-Based Analytical Devices ? Applications to Viscosity Measurements in Saliva Analysis and Protease-Activity Assays en-subtitle= kn-subtitle= en-abstract= kn-abstract=We designed and developed a microcontroller-integrated multichannel time detection system that uses a microfluidic paper-based analytical device (?PAD) to measure liquid viscosity. This detection system is equipped with ten detectors to enhance the throughput of the measurements. The ?PAD utilizes capillary action to determine viscosity based on the flow time of a liquid sample. A conductivity detection system begins counting the flow time when a sample is introduced and stops the count when the sample reaches the detection electrode. Sodium chloride (NaCl) was pre-deposited in the detection channel of the ?PAD to enhance the conductivity of non-conductive samples, and Grade 1 CHR chromatography paper was selected as the optimal vehicle for substrates after comparing various channel widths, paper types, and channel lengths. The device demonstrated a linear correlation between flow time and viscosity for bovine serum albumin (BSA) and glucose solutions, which validates the theoretical model. The time readout measured protease activity when gelatin was used as a substrate and revealed an activity order of bromelain?>?papain?>?trypsin. The practical applicability of this system was further confirmed by testing real saliva samples, which demonstrated that the viscosity of saliva decreases rapidly after collection. Moreover, the results indicate that saliva viscosity was increased during extended durations of exercise. Overall, this ?PAD system provides a simple, low-cost, and portable solution for viscosity measurement, with potential applications in clinical diagnostics and field measurements. en-copyright= kn-copyright= en-aut-name=RenJianchao en-aut-sei=Ren en-aut-mei=Jianchao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DanchanaKaewta en-aut-sei=Danchana en-aut-mei=Kaewta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanetaTakashi en-aut-sei=Kaneta en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Chemistry, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry, Okayama University kn-affil= en-keyword=Paper-based analytical device kn-keyword=Paper-based analytical device en-keyword=Time detector kn-keyword=Time detector en-keyword=Multichannel kn-keyword=Multichannel en-keyword=Viscosity kn-keyword=Viscosity en-keyword=Enzyme assay kn-keyword=Enzyme assay en-keyword=Saliva kn-keyword=Saliva END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=5 article-no= start-page=e70145 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260821 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Transforming Life Science Through Chromosome‐Level Genome Assemblies en-subtitle= kn-subtitle= en-abstract= kn-abstract=Advances in long-read sequencing and Hi?C scaffolding have made chromosome-level genome assembly increasingly accessible to individual laboratories, shifting genome research from large consortium-led projects toward investigator-driven studies across diverse taxa. This transition allows researchers to select organisms based on biological questions rather than the prior availability of genomic resources. In this review, we summarize the core experimental and computational steps for generating, evaluating, and annotating chromosome-level assemblies, and examine how they have advanced research in non-model organisms and genetically complex systems. Representative case studies illustrate four major contributions: resolving structural variation and lineage-specific genome architecture, linking genome organization to phenotypic innovation and plasticity, reconstructing deep chromosome evolution and macrosynteny, and distinguishing homologous and homoeologous chromosomes in polyploid genomes. These examples show that chromosome-level assemblies provide more than complete reference sequences. They establish a continuous genomic coordinate system through which genes, regulatory elements, transposable element insertions, sequence variants, and cellular states can be interpreted within broader chromosomal, population, and evolutionary contexts. We describe this integrative perspective as “glocal biology.” Future progress will require pangenomic, population-scale, and haplotype-resolved resources integrated with multi-omics and functional analyses. Collectively, chromosome-level genomics is reshaping life science by embedding molecular functions within chromosomal and evolutionary contexts. en-copyright= kn-copyright= en-aut-name=KonTetsuo en-aut-sei=Kon en-aut-mei=Tetsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KataokaKosuke en-aut-sei=Kataoka en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LuoYi‐Jyun en-aut-sei=Luo en-aut-mei=Yi‐Jyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WibisanaJohannes Nicolaus en-aut-sei=Wibisana en-aut-mei=Johannes Nicolaus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TogaKouhei en-aut-sei=Toga en-aut-mei=Kouhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UnoNarumi en-aut-sei=Uno en-aut-mei=Narumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MondenYuki en-aut-sei=Monden en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HamadaMayuko en-aut-sei=Hamada en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Neurosciences and Developmental Biology, University of Vienna kn-affil= affil-num=2 en-affil=Graduate School of Engineering, Tokyo University of Agriculture and Technology kn-affil= affil-num=3 en-affil=Biodiversity Research Center, Academia Sinica kn-affil= affil-num=4 en-affil=Genomics and Regulatory Systems Unit, Okinawa Institute of Science and Technology Graduate University kn-affil= affil-num=5 en-affil=Laboratory of BioDX, PtBio Co‐Creation Research Center, Genome Editing Innovation Center, Hiroshima University kn-affil= affil-num=6 en-affil=Laboratory of Bioengineering, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=8 en-affil=Ushimado Marine Institute, Okayama University kn-affil= en-keyword=chromosome-level genome assembly kn-keyword=chromosome-level genome assembly en-keyword=genome evolution kn-keyword=genome evolution en-keyword=Hi?C scaffolding kn-keyword=Hi?C scaffolding en-keyword=long-read sequencing kn-keyword=long-read sequencing en-keyword=non-model animals kn-keyword=non-model animals END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=6 article-no= start-page=e202500237 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=NUAK2 Inhibition Enhances Macromolecular Drug Delivery in a 3D Fibrotic Model of the Pancreatic Tumor Microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pancreatic ductal adenocarcinoma (PDAC) features a fibrotic tumor microenvironment that impedes drug delivery and significantly limits the successful clinical application of nanomedicines. Targeting signaling in pancreatic stellate cells (PSCs), which drive fibrosis via excessive secretion of extracellular matrix proteins such as collagen I, may be useful in overcoming this fibrotic barrier. The AMPK-related kinases NUAK1/2 have recently gained interest as promoters of fibrosis, but whether they play a profibrotic role in PSCs remains unknown. Here, patient PSCs are used to assess NUAK1/2 involvement in the PDAC fibrotic barrier. Leveraging a 3D cell culture model of PDAC fibrosis, the effect of targeting NUAK1/2 on the permeability of macromolecular dextrans of various sizes, as well as physiologically relevant macromolecules, albumin and IgG, and clinical nanomedicines, Doxil and Abraxane, is investigated. NUAK1/2 inhibition is shown to diminish collagen I to enhance macromolecular permeability, via a mechanism independent of established pathways involving transforming growth factor-β (TGFβ) and yes-associated protein (YAP). Through isoform-specific knockdown, predominant NUAK2 involvement is demonstrated. Mechanistically, actin stress fiber regulation by NUAK2 is shown to be important. Altogether, these results show in?vitro that NUAK2 promotes fibrotic signaling in PSCs and may be targeted to enhance macromolecular drug delivery in PDAC. en-copyright= kn-copyright= en-aut-name=NakamuraMisaki en-aut-sei=Nakamura en-aut-mei=Misaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=OhiraMayu en-aut-sei=Ohira en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Ohta‐OkanoHaruko en-aut-sei=Ohta‐Okano en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraReika en-aut-sei=Nakamura en-aut-mei=Reika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SenoYu en-aut-sei=Seno en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YaraSaaya en-aut-sei=Yara en-aut-mei=Saaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujitaSakura en-aut-sei=Fujita en-aut-mei=Sakura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShibataDaichi en-aut-sei=Shibata en-aut-mei=Daichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoMasaya en-aut-sei=Yamamoto en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OsadaKensuke en-aut-sei=Osada en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=MasamuneAtsushi en-aut-sei=Masamune en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KanoMitsunobu R. en-aut-sei=Kano en-aut-mei=Mitsunobu R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Materials Processing Graduate School of Engineering, Tohoku University kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Molecular Imaging and Theranostics Institute for Quantum Medical Science, National Institutes for Quantum Sciences and Technology (QST) kn-affil= affil-num=13 en-affil=Department of Bioengineering Graduate School of Engineering, The University of Tokyo kn-affil= affil-num=14 en-affil=Division of Gastroenterology Graduate School of Medicine, Tohoku University kn-affil= affil-num=15 en-affil=Department of Pharmaceutical Biomedicine Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=fibrosis kn-keyword=fibrosis en-keyword=nanomedicine kn-keyword=nanomedicine en-keyword=NUAK kinase kn-keyword=NUAK kinase en-keyword=pancreatic cancer kn-keyword=pancreatic cancer en-keyword=tumor microenvironment kn-keyword=tumor microenvironment END start-ver=1.4 cd-journal=joma no-vol=82 cd-vols= no-issue=10 article-no= start-page=26-1707 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=A Bayesian Approach to ADC-to-Dose Conversion in Radiochromic Film Dosimetry kn-title=ベイズ推定を用いたラジオクロミックフィルムのADC値?線量変換法 en-subtitle= kn-subtitle= en-abstract=Purpose: Radiochromic film is widely used for patient-specific intensity-modulated radiation therapy quality assurance (IMRT QA) because of its high spatial resolution. However, calibration for converting pixel values to dose requires irradiation at multiple known dose levels, resulting in a substantial workload. Consequently, in some institutions, calibration is performed only under limited circumstances, such as when the film lot changes. This study aimed to develop and validate a Bayesian inference model that estimates the calibration curve using previously acquired calibration datasets together with the unirradiated pixel value of the target film, thereby improving the efficiency of the calibration process. Methods: A total of 93 calibration datasets acquired using TomoHD were analyzed. A quadratic polynomial regression model was constructed with dose and elapsed time from irradiation to scanning as explanatory variables. Separate models were developed for each scanner orientation (portrait and landscape), and the intercept was estimated using the unirradiated pixel value of the target film. Bayesian inference was performed using Stan, and model convergence was evaluated by trace plots and the Rhat statistic. Model performance was validated using 10 EBT4 films from a different lot by comparing predicted and measured pixel values and evaluating dose errors. Results: All models showed good convergence, with Rhat values below 1.01. For the validation films, the pixel value error was less than 3.6%, and the coefficient of determination (R2) exceeded 0.99. The mean dose error was 2.7±1.3?cGy at 24.0?cGy and 37.5±12.8?cGy at 868.2?cGy. The maximum dose error was 66.6?cGy at 710.6?cGy. Conclusion: The proposed method demonstrated the feasibility of estimating the calibration curve using previously acquired calibration datasets and the unirradiated pixel value of the target film. This approach has the potential to improve the efficiency of radiochromic film calibration. Future studies should apply this method to patient-specific IMRT QA and investigate its impact on dose distribution evaluation. kn-abstract=【目的】ラジオクロミックフィルムは高い空間分解能を有することから，患者別IMRT品質保証（IMRT QA）に広く利用されている．一方，ピクセル値を線量へ変換するためのキャリブレーションには，複数の既知線量で照射したフィルムが必要であり，作業負担が大きいことから，施設によってはフィルムロット変更時などに限定して実施される場合がある．本研究では，過去のキャリブレーションデータセットと対象フィルムの未照射時ピクセル値を用いてキャリブレーション曲線を推定するベイズ推定モデルを構築し，キャリブレーション作業の効率化を目的としてその有用性を検証した．【方法】TomoHDを用いて取得した93組のキャリブレーションデータセットを解析対象とした．線量および照射からスキャンまでの経過時間を説明変数とする二次多項式回帰モデルを構築した．モデルはスキャナの読み取り方向（縦方向・横方向）ごとに作成し，対象フィルムの未照射時ピクセル値を切片項として推定した．ベイズ推定にはStanを用い，トレースプロットおよびRhat統計量により収束性を評価した．更にモデル性能の評価には，異なるロットのEBT4フィルム10枚を用いて予測ピクセル値と実測値を比較するとともに，線量誤差を評価した．【結果】すべてのモデルでRhatは1.01未満を示し，良好な収束性が確認された．検証用フィルムでは，ピクセル値の誤差は3.6%未満，決定係数（R2）は0.99以上であった．また，線量誤差は24?cGyで平均2.7?cGy（SD 1.3），868.2?cGyで平均37.5?cGy（SD 12.8）であり，最大線量誤差は710.6?cGyにおいて66.6?cGyであった．【結語】本手法は，過去のキャリブレーションデータセットと対象フィルムの未照射時ピクセル値を用いてキャリブレーション曲線を推定できる可能性を示した．また，ラジオクロミックフィルムのキャリブレーション作業の効率化に寄与する可能性が示唆された．今後は患者別IMRT QAに適用し，線量分布評価への影響を検証する必要がある． en-copyright= kn-copyright= en-aut-name=TanimotoYuki en-aut-sei=Tanimoto en-aut-mei=Yuki kn-aut-name=谷本 祐樹 kn-aut-sei=谷本 kn-aut-mei=祐樹 aut-affil-num=1 ORCID= en-aut-name=SugimotoKohei en-aut-sei=Sugimoto en-aut-mei=Kohei kn-aut-name=杉本 昂平 kn-aut-sei=杉本 kn-aut-mei= 昂平 aut-affil-num=2 ORCID= en-aut-name=TamoriMasahide en-aut-sei=Tamori en-aut-mei=Masahide kn-aut-name=田盛 雅英 kn-aut-sei=田盛 kn-aut-mei=雅英 aut-affil-num=3 ORCID= en-aut-name=YatsukiMiho en-aut-sei=Yatsuki en-aut-mei=Miho kn-aut-name=八木 美保 kn-aut-sei=八木 kn-aut-mei=美保 aut-affil-num=4 ORCID= en-aut-name=YoshidaShohei en-aut-sei=Yoshida en-aut-mei=Shohei kn-aut-name=吉田 昌平 kn-aut-sei=吉田 kn-aut-mei= 昌平 aut-affil-num=5 ORCID= en-aut-name=SugaharaKazuma en-aut-sei=Sugahara en-aut-mei=Kazuma kn-aut-name=菅原 一真 kn-aut-sei=菅原 kn-aut-mei=一真 aut-affil-num=6 ORCID= en-aut-name=OitaMasataka en-aut-sei=Oita en-aut-mei=Masataka kn-aut-name=笈田 将皇 kn-aut-sei=笈田 kn-aut-mei=将皇 aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Radiology, NHO Iwakuni Clinical Center kn-affil=NHO岩国医療センター放射線科 affil-num=2 en-affil=Department of Radiological Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare kn-affil=川崎医療福祉大学医療技術学部診療放射線技術学科 affil-num=3 en-affil=Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center kn-affil=NHO呉医療センター・中国がんセンター中央放射線センター affil-num=4 en-affil=Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center kn-affil=NHO呉医療センター・中国がんセンター中央放射線センター affil-num=5 en-affil=Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center kn-affil=NHO呉医療センター・中国がんセンター中央放射線センター affil-num=6 en-affil=Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center kn-affil=NHO呉医療センター・中国がんセンター中央放射線センター affil-num=7 en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 en-keyword=radiation therapy kn-keyword=radiation therapy en-keyword=quality assurance kn-keyword=quality assurance en-keyword=patient-specific IMRT QA kn-keyword=patient-specific IMRT QA en-keyword=radiochromic film kn-keyword=radiochromic film en-keyword=Bayesian inference kn-keyword=Bayesian inference END start-ver=1.4 cd-journal=joma no-vol=165 cd-vols= no-issue=7 article-no= start-page=074308 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260821 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High-resolution analysis of the S1?S0 transition of magnesium phthalocyanine: Rotational structure and electronic angular momentum en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a high-resolution spectroscopic analysis of the S1?S0 transition of magnesium phthalocyanine (MgPc), obtained by probing buffer-gas-cooled molecules with a narrow-linewidth laser. The observed spectrum exhibits a characteristic three-peak pattern, which is well reproduced by modeling MgPc as an oblate symmetric top with D4h symmetry. A key result of this work is that the spectrum is strongly influenced by electronic Coriolis coupling, which is associated with electronic angular momentum. The electronic Coriolis constant is determined to be ?2, indicating an effective orbital angular momentum of about 2 in the excited S1 state, originating from the π-conjugated ring excitation. This provides a direct spectroscopic signature of electronic angular momentum in a large polyatomic molecule. The presence of nonzero electronic orbital angular momentum is qualitatively consistent with the perimeter model of phthalocyanines. The value lies within the range inferred from previous magnetic circular dichroism (MCD) studies. Compared with the previous MCD estimate, the present analysis provides a more state-specific and narrower constraint, demonstrating that high-resolution spectroscopy enables direct access to electronic and magnetic properties beyond conventional structural characterization. en-copyright= kn-copyright= en-aut-name=MiyamotoYuki en-aut-sei=Miyamoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EnomotoKatsunari en-aut-sei=Enomoto en-aut-mei=Katsunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IwakuniKana en-aut-sei=Iwakuni en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KumaSusumu en-aut-sei=Kuma en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadaKoichi M. T. en-aut-sei=Yamada en-aut-mei=Koichi M. T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Physics, University of Toyama kn-affil= affil-num=3 en-affil=Institute for Laser Science, University of Electro-Communications kn-affil= affil-num=4 en-affil=Department of Physics, Rikkyo University kn-affil= affil-num=5 en-affil=Institute for Laser Science, University of Electro-Communications kn-affil= END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=11 article-no= start-page=1302 end-page=1313 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trastuzumab-Pertuzumab Plus Eribulin or Taxane as First-Line Chemotherapy for Human Epidermal Growth Factor 2?Positive Locally Advanced/Metastatic Breast Cancer: The Randomized Noninferiority Phase III EMERALD Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Trastuzumab-pertuzumab (HP) plus taxane is a current standard first-line therapy for recurrent or metastatic human epidermal growth factor 2 (HER2)+ breast cancer (BC). We investigated noninferiority of eribulin to a taxane when combined with dual HER2 blockade as first-line systemic treatment for locally advanced/metastatic HER2+ BC.
Methods In the phase III EMERALD trial (target sample size, 480; ClinicalTrials.gov identifier: NCT03264547/UMIN000027938), patients were randomly assigned (1:1) to receive eribulin 1.4 mg/m2 once daily on days 1 and 8 (eribulin group) or a taxane (docetaxel 75 mg/m2 once on day 1 or paclitaxel 80 mg/m2 once daily on days 1, 8, and 15; taxane group) intravenously in a 21-day cycle, each with HP on day 1. The primary end point was progression-free survival (PFS; intention-to-treat population). Secondary end points included objective response rate, overall survival (OS), patient-reported quality of life (QoL), and safety. Noninferiority was tested using the stratified Cox proportional hazards model to estimate hazard ratios (HRs) for PFS events, with a noninferiority HR margin of 1.33.
Results Between August 2017 and June 2021, 446 patients (median age, 56.0 years) were enrolled. The median PFS was 14.0 and 12.9 months in the eribulin group (n = 224) and taxane group (n = 222 [docetaxel/paclitaxel, n = 186/36]), respectively (HR, 0.95 [95% CI, 0.76 to 1.19]), which confirmed the noninferiority of the study regimen. The median OS was 65.3 months in the taxane group but has not been reached in the eribulin group. Median time to QoL deterioration was numerically longer with eribulin than with taxane. Adverse event (AE) rates were similar, despite the longer duration of eribulin use. Infusion reaction, skin-related AEs, diarrhea, and edema were more common with taxane, whereas neutropenia was more common with eribulin.
Conclusion The results suggested that eribulin + HP is an option for first-line treatment of locally advanced/metastatic HER2+ BC. en-copyright= kn-copyright= en-aut-name=YamashitaToshinari en-aut-sei=Yamashita en-aut-mei=Toshinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SajiShigehira en-aut-sei=Saji en-aut-mei=Shigehira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakanoToshimi en-aut-sei=Takano en-aut-mei=Toshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaitoYoichi en-aut-sei=Naito en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuneizumiMichiko en-aut-sei=Tsuneizumi en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshimuraAkiyo en-aut-sei=Yoshimura en-aut-mei=Akiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiMasato en-aut-sei=Takahashi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsurutaniJunji en-aut-sei=Tsurutani en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwataniTsuguo en-aut-sei=Iwatani en-aut-mei=Tsuguo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitadaMasahiro en-aut-sei=Kitada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TadaHiroshi en-aut-sei=Tada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoriNatsuko en-aut-sei=Mori en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HiguchiToru en-aut-sei=Higuchi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwasaTsutomu en-aut-sei=Iwasa en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ArakiKazuhiro en-aut-sei=Araki en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KoizumiKei en-aut-sei=Koizumi en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HasegawaHiroki en-aut-sei=Hasegawa en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UchidaYohei en-aut-sei=Uchida en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MoritaSatoshi en-aut-sei=Morita en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MasudaNorikazu en-aut-sei=Masuda en-aut-mei=Norikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Breast Surgery and Oncology, Kanagawa Cancer Center kn-affil= affil-num=2 en-affil=Department of Medical Oncology, Fukushima Medical University kn-affil= affil-num=3 en-affil=Department of Breast Medical Oncology, The Cancer Institute Hospital of JFCR kn-affil= affil-num=4 en-affil=Department of General Internal Medicine, National Cancer Center Hospital East kn-affil= affil-num=5 en-affil=Department of Breast Surgery, Shizuoka General Hospital kn-affil= affil-num=6 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=7 en-affil=Department of Breast Surgery, Hokkaido University Hospital kn-affil= affil-num=8 en-affil=Advanced Cancer Translational Research Institute, Showa University kn-affil= affil-num=9 en-affil=Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Breast Disease Center, Asahikawa Medical University Hospital kn-affil= affil-num=11 en-affil=Department of Surgery, Division of Breast and Endocrine Surgery, Tohoku University Hospital kn-affil= affil-num=12 en-affil=Department of Breast Surgery, Seirei Hamamatsu General Hospital kn-affil= affil-num=13 en-affil=Department of Breast Unit, Japanese Red Cross Saitama Hospital kn-affil= affil-num=14 en-affil=Department of Medical Oncology, Kindai University Hospital kn-affil= affil-num=15 en-affil=Department of Breast Medical Oncology, Gunma Prefectural Cancer Center kn-affil= affil-num=16 en-affil=Department of Surgery 1, Division of Breast Surgery, Hamamatsu University School of Medicine kn-affil= affil-num=17 en-affil=Medical HQs, Eisai Co, Ltd kn-affil= affil-num=18 en-affil=Medical HQs, Eisai Co, Ltd kn-affil= affil-num=19 en-affil=Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University kn-affil= affil-num=20 en-affil=Department of Breast Surgery, Graduate School of Medicine, Kyoto University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=5 article-no= start-page=68 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Primary angiosarcoma of the breast: a literature review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Objective: Primary angiosarcoma of the breast (PBA) is an extremely rare and heterogeneous disease. PBA is difficult to diagnose and has a poor prognosis. In order to better understand the disease and provide evidence-based treatment for PBA patients, a review of the published literature in the English language was conducted.
Methods: A literature review in agreement with the PRISMA protocol was conducted. Medline and Cochrane databases were searched for English articles on PBA patients in September 2023 with a predetermined strategy. The articles were categorized and assessed based on hierarchical levels of scientific evidence.
Key Content and Findings: A total of 255 articles were identified, among these 137 publications which included 1,888 patients met the criteria for inclusion in the final analysis. No prospective, randomized trials exclusive to PBA have been recognized. This article provides an overview of the most current and comprehensive evidence concerning the epidemiology, etiology, genomic features, clinical presentations, diagnosis, treatment, and prognosis of PBA.
Conclusions: Despite the fact that current evidence is largely derived from retrospective studies, database analyses, and case reports, we utilized this information to tackle important clinical questions concerning optimal patient management practices for PBA. Complete surgical excision continues to be the mainstay treatment for PBA. However, the effectiveness of adjuvant therapies is still unclear. This narrative review highlights the urgent need for more rigorously designed research to enhance the management and treatment strategies for PBA. en-copyright= kn-copyright= en-aut-name=ZhuYidan en-aut-sei=Zhu en-aut-mei=Yidan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamotoShogo en-aut-sei=Nakamoto en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsukiokiTakahiro en-aut-sei=Tsukioki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiYuko en-aut-sei=Takahashi en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwataniYoko en-aut-sei=Iwatani en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwataniTsuguo en-aut-sei=Iwatani en-aut-mei=Tsuguo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhangXinfeng en-aut-sei=Zhang en-aut-mei=Xinfeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TaniokaMaki en-aut-sei=Tanioka en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Breast Surgery, Liaoning Cancer Hospital & Institute kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Breast Surgery, Liaoning Cancer Hospital & Institute kn-affil= affil-num=8 en-affil=Department of Clinical AI Human Resources Development Program, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=Primary angiosarcoma of the breast (PBA) kn-keyword=Primary angiosarcoma of the breast (PBA) en-keyword=complete surgical excision kn-keyword=complete surgical excision en-keyword=hierarchal levels of scientific evidence kn-keyword=hierarchal levels of scientific evidence en-keyword=literature review kn-keyword=literature review 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= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260820 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Performance of generative artificial intelligence in oral and maxillofacial radiology based on the board-certification examination of Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective To evaluate the performance and potential utility of generative artificial intelligence (AI) in oral and maxillofacial radiology using the board-certification examination administered by the Japanese Society for Oral and Maxillofacial Radiology (JSOMR).
Methods The responses generated by ChatGPT for multiple-choice questions from the board-certification examination of the JSOMR over the three-year period from 2020 to 2022 were assessed. The questions were manually entered individually as prompts for GPT-3.5, GPT-4, and GPT-5, which are the models available from ChatGPT. The accuracy was calculated according to examination year, question format, and level of taxonomy.
Results GPT-3.5 achieved an accuracy of 40.3% for the three years (42.9%, 42.0%, and 36.0% for 2020, 2021, and 2022, respectively), that of GPT-4 was 67.8% (67.3%, 74.0%, and 62.0%, respectively), and that of GPT-5 was 76.5% (79.6%, 78.0%, and 72.0%, respectively). GPT-5’s results exceeded the passing score for each year with the accuracy significantly outperformed that of GPT-3.5 and GPT-4. Regarding performance according to the question format, GPT-5 performed significantly superior to the earlier models, especially on two-answer questions.
Conclusions On the board-certification examination of the JSOMR, the performance of GPT-5 was significantly superior to that of GPT-3.5 and GPT-4. This suggests that, given the rapid development of generative AI, GPT-5 has reached a level of text-based knowledge equivalent to that assessed in the board-certification examination of the JSOMR. 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=KawazuToshiyuki en-aut-sei=Kawazu en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=5 ORCID= en-aut-name=ShibanumaAkira en-aut-sei=Shibanuma en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NambaYuri en-aut-sei=Namba en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaSuzuka en-aut-sei=Yoshida en-aut-mei=Suzuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshidaSaori en-aut-sei=Yoshida en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakamuraYoshihide en-aut-sei=Nakamura en-aut-mei=Yoshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YanagiYoshinobu en-aut-sei=Yanagi en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Medical Development Field, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Radiology, Medical Development Field, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Radiology, Medical Development Field, Okayama University kn-affil= affil-num=6 en-affil=Department of Community and Global Health, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Radiology, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Radiology, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=9 en-affil=Preliminary Examination Room, Medical Development Field, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Artificial intelligence kn-keyword=Artificial intelligence en-keyword=Generative artificial intelligence kn-keyword=Generative artificial intelligence en-keyword=ChatGPT kn-keyword=ChatGPT en-keyword=Large language model kn-keyword=Large language model en-keyword=Radiology kn-keyword=Radiology en-keyword=Education kn-keyword=Education 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=10 cd-vols= no-issue=10 article-no= start-page=101308 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Inhibition of Scarb1 on Endothelial Cells Attenuates Pressure Overload-Induced Heart Failure Progression en-subtitle= kn-subtitle= en-abstract= kn-abstract=Inappropriate endothelial cell (EC) interactions contribute to heart failure; however, their precise mechanisms remain poorly understood. This study investigated EC-fibroblast interactions mediated by Scarb1 using single-cell RNA-sequencing analysis in a mouse heart failure model. ECs exhibited inflammatory and fibrotic gene expression, with Scarb1-mediated fibroblast-EC interactions driving disease progression. EC-specific Scarb1 knockout and systemic SCARB1 inhibition attenuated heart failure progression. In vitro and spatial omics analyses confirmed the role of SCARB1 in ECs and cell-cell interaction during heart failure progression. These findings highlight SCARB1 as a promising therapeutic target for EC-focused interventions. en-copyright= kn-copyright= en-aut-name=KatsukiToshiomi en-aut-sei=Katsuki en-aut-mei=Toshiomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KusumotoDai en-aut-sei=Kusumoto en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AkibaYohei en-aut-sei=Akiba en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KimuraMai en-aut-sei=Kimura en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KomuroJin en-aut-sei=Komuro en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraTakahiro en-aut-sei=Nakamura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HashimotoHisayuki en-aut-sei=Hashimoto en-aut-mei=Hisayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoukaThukaa en-aut-sei=Kouka en-aut-mei=Thukaa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugaiKazuhisa en-aut-sei=Sugai en-aut-mei=Kazuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatsumataYoshinori en-aut-sei=Katsumata en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MiyasakaMasaki en-aut-sei=Miyasaka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SuzukiYutaka en-aut-sei=Suzuki en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KuramotoJunko en-aut-sei=Kuramoto en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KubotaYoshiaki en-aut-sei=Kubota en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FukudaKeiichi en-aut-sei=Fukuda en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 ORCID= en-aut-name=IedaMasaki en-aut-sei=Ieda en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=4 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=5 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=6 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=8 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=9 en-affil=Institute for Integrated Sports Medicine, School of Medicine, Keio University kn-affil= affil-num=10 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=11 en-affil=Department of Computational Biology and Medical Sciences, the University of Tokyo kn-affil= affil-num=12 en-affil=Department of Computational Biology and Medical Sciences, the University of Tokyo kn-affil= affil-num=13 en-affil=Department of Pathology, Keio University School of Medicine kn-affil= affil-num=14 en-affil=Department of Anatomy, Keio University School of Medicine kn-affil= affil-num=15 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=16 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= en-keyword=endothelial cells kn-keyword=endothelial cells en-keyword=fibroblasts kn-keyword=fibroblasts en-keyword=heart failure kn-keyword=heart failure en-keyword=SCARB1 kn-keyword=SCARB1 END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue=1 article-no= start-page=97 end-page=112 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vaccination in paediatric, adolescent, and transitional-age rheumatic diseases: a systematic review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: This systematic review evaluated the efficacy and safety of vaccination in patients with paediatric, adolescent, and transitional-age rheumatic diseases as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement.
Methods: An independent investigator systematically searched PubMed to identify relevant studies published by September 2022. The search results were divided into vaccines or toxoids for diphtheria, pertussis, tetanus, pneumococcus, influenza virus, hepatitis A virus, hepatitis B virus, human papillomavirus, poliovirus, measles virus, mumps virus, rubella virus, varicella zoster virus, and tuberculosis.
Results: A meta-analysis was not feasible due to the lack of randomized controlled trials with standardized patient backgrounds and conditions. Non-live vaccines are generally immunogenic and safe for patients with rheumatic diseases. In contrast, live attenuated vaccines should usually be withheld in patients on immunosuppressants, corticosteroids, biologics, or Janus kinase inhibitors. However, for necessary immunizations against measles, rubella, mumps, or varicella, live attenuated vaccines may be considered for patients receiving low-dose corticosteroids, methotrexate, or tumour necrosis factor inhibitors.
Conclusions This review highlights the significant gap in evidence for paediatric populations compared with adults, particularly concerning new biological therapies and Janus kinase inhibitors. Further evidence is needed regarding vaccination in paediatric patients with rheumatic diseases. en-copyright= kn-copyright= en-aut-name=OhnishiTakuma en-aut-sei=Ohnishi en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WakiguchiHiroyuki en-aut-sei=Wakiguchi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshimoriShingo en-aut-sei=Ishimori en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItohNaohiro en-aut-sei=Itoh en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamazakiSusumu en-aut-sei=Yamazaki en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkafujiIkuo en-aut-sei=Okafuji en-aut-mei=Ikuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhtomoYoshiyuki en-aut-sei=Ohtomo en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KobayashiIchiro en-aut-sei=Kobayashi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pediatrics, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Pediatrics, Kobe University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Faculty of Medical Sciences, Department of Pediatrics, University of Fukui kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Pediatrics, Kobe City Medical Center General Hospital kn-affil= affil-num=8 en-affil=Department of Pediatrics, Juntendo University Nerima Hospital kn-affil= affil-num=9 en-affil=Center for Pediatric Allergy and Rheumatology, KKR Sapporo Medical Center kn-affil= en-keyword=Bacille Calmette?Gu?rin kn-keyword=Bacille Calmette?Gu?rin en-keyword=diphtheria, pertussis, and tetanus vaccine kn-keyword=diphtheria, pertussis, and tetanus vaccine en-keyword=hepatitis A virus vaccine kn-keyword=hepatitis A virus vaccine en-keyword=hepatitis B virus vaccine kn-keyword=hepatitis B virus vaccine en-keyword=human papillomavirus vaccine kn-keyword=human papillomavirus vaccine en-keyword=inactivated polio vaccine kn-keyword=inactivated polio vaccine en-keyword=influenza vaccine kn-keyword=influenza vaccine en-keyword=measles, mumps, and rubella vaccine kn-keyword=measles, mumps, and rubella vaccine en-keyword=pneumococcal vaccine kn-keyword=pneumococcal vaccine en-keyword=varicella zoster virus vaccine kn-keyword=varicella zoster virus vaccine END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260727 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Workforce and institutional factors associated with comprehensive genomic profiling utilization in gynecologic oncology: a nationwide questionnaire survey in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Comprehensive genomic profiling (CGP) has been widely introduced into precision oncology; however, its real-world implementation in gynecologic oncology remains unclear. This study evaluated nationwide CGP utilization, treatment translation, and management of secondary germline findings in Japanese gynecologic oncology.
Methods A nationwide survey was conducted across 98 institutions participating in gynecologic oncology training and/or Japan’s cancer genomic medicine network. Institutional characteristics, workforce composition, treatment translation, and management of germline findings were assessed. Associations between institutional factors and CGP utilization or trial-related treatment translation were analyzed using incidence rate ratios (IRRs) with 95% confidence intervals.
Results Among 68 institutions with complete CGP volume data, 6,964 CGP tests were performed, including 922 for gynecologic malignancies. The median number of gynecologic CGP tests per institution was 10. In multivariate analysis, the number of board-certified obstetrician?gynecologists was associated with CGP utilization (IRR, 1.05; 95% CI 1.01?1.08). CGP-guided therapy was delivered to 80 patients (8.7%). Trial-related treatment translation was associated with the number of board-certified obstetrician?gynecologists (IRR, 1.09; 95% CI 1.02?1.16) and the presence of a medical oncology department (IRR, 7.93; 95% CI 1.41?44.72). Presumed germline pathogenic variants were identified in 100 cases (10.8%); however, confirmatory germline testing was performed in only 38 cases.
Conclusion CGP utilization in Japanese gynecologic oncology was associated with gynecologic workforce capacity and multidisciplinary genomic infrastructure. Collaboration between gynecologic oncology and medical oncology may facilitate treatment translation. CGP may also serve as an entry point for hereditary cancer evaluation despite incomplete downstream germline evaluation. en-copyright= kn-copyright= en-aut-name=SudoTamotsu en-aut-sei=Sudo en-aut-mei=Tamotsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MasudaKenta en-aut-sei=Masuda en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OdaKatsutoshi en-aut-sei=Oda en-aut-mei=Katsutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatariHidemichi en-aut-sei=Watari en-aut-mei=Hidemichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoShinya en-aut-sei=Sato en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaranoKenichi en-aut-sei=Harano en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagaseSatoru en-aut-sei=Nagase en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakeharaKazuhiro en-aut-sei=Takehara en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MandaiMasaki en-aut-sei=Mandai en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SasajimaYuko en-aut-sei=Sasajima en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YanaiHirouki en-aut-sei=Yanai en-aut-mei=Hirouki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TsudaHitoshi en-aut-sei=Tsuda en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KobayashiYusuke en-aut-sei=Kobayashi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KawanaKei en-aut-sei=Kawana en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MikamiMikio en-aut-sei=Mikami en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KatoKiyoko en-aut-sei=Kato en-aut-mei=Kiyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=AokiDaisuke en-aut-sei=Aoki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OkamotoAikou en-aut-sei=Okamoto en-aut-mei=Aikou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Cancer Genetics and Genomics, School of Medicine, Fujita Health University kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Division of Integrative Genomics, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University kn-affil= affil-num=5 en-affil=Department of Clinical Genomic Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Tottori University School of Medicine kn-affil= affil-num=7 en-affil=Department of Medical Oncology, National Cancer Center Hospital East kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Yamagata University kn-affil= affil-num=9 en-affil=Department of Gynecologic Oncology, NHO Shikoku Cancer Center kn-affil= affil-num=10 en-affil=Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Pathology, Teikyo University Hospital kn-affil= affil-num=12 en-affil=Department of Pathology, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Basic Pathology, National Defense Medical College kn-affil= affil-num=14 en-affil=Department of Obstetrics and Gynecology, Institute of Medicine, University of Tsukuba kn-affil= affil-num=15 en-affil=Department of Obstetrics and Gynecology, Nihon University School of Medicine kn-affil= affil-num=16 en-affil=Department of Medical Science, Shonan University of Medical Science kn-affil= affil-num=17 en-affil=Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=18 en-affil=International University of Health and Welfare Graduate School kn-affil= affil-num=19 en-affil=Department of Obstetrics and Gynecology, The Jikei University School of Medicine kn-affil= en-keyword=Comprehensive genomic profiling kn-keyword=Comprehensive genomic profiling en-keyword=Gynecological oncology kn-keyword=Gynecological oncology en-keyword=Precision oncology kn-keyword=Precision oncology en-keyword=Cancer genomic medicine kn-keyword=Cancer genomic medicine en-keyword=Organ-specialty?led implementation kn-keyword=Organ-specialty?led implementation en-keyword=Germline findings kn-keyword=Germline findings END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=8 article-no= start-page=494 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260807 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oral Supplementation of Bacillus subtilis Attenuated Alveolar Bone Loss in a Mouse Model of Ligature-Induced Periodontitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: This study aimed to investigate the effects of oral Bacillus subtilis (BS) on alveolar bone loss, intestinal morphology, and gut microbiota in a mouse model of ligature-induced periodontitis. Methods: A total of 24 male C57BL/6J mice (6 weeks old) were allocated to control, periodontitis (P), BS, and BS+P groups. Periodontitis was induced by bilateral ligation of maxillary second molars, and BS was orally administered for 18 consecutive days. Gut microbiota composition was analyzed by 16S rDNA sequencing, alveolar bone loss and gut morphology were evaluated using ImageJ version 1.54g, and ELISA-detectable serum vitamin D metabolite concentrations were measured using an enzyme-linked immunosorbent assay. Results: Compared with the P group, the BS+P group showed reduced bone loss. Serum vitamin D metabolite concentrations, small-intestine villus height, and villus height-to-crypt depth ratios were higher in the BS+P group. In gut microbiota, alpha diversity differed significantly among groups based on the Shannon index. Bray?Curtis-based beta diversity differed significantly among groups. Conclusions: Oral supplementation of BS attenuated the progression of ligature-induced periodontitis in a mouse model, and changes in gut microbiota may be associated with this effect. en-copyright= kn-copyright= en-aut-name=ZhangYixuan en-aut-sei=Zhang en-aut-mei=Yixuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ToyamaNaoki en-aut-sei=Toyama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NurhamimMohammad en-aut-sei=Nurhamim en-aut-mei=Mohammad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakaharaMomoko en-aut-sei=Nakahara en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukuharaDaiki en-aut-sei=Fukuhara en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaruyamaTakayuki en-aut-sei=Maruyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Dental School, Okayama University kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Dental School, Okayama University kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Bacillus subtilis kn-keyword=Bacillus subtilis en-keyword=periodontitis kn-keyword=periodontitis en-keyword=alveolar bone loss kn-keyword=alveolar bone loss en-keyword=gut microbiota kn-keyword=gut microbiota en-keyword=intestinal morphology kn-keyword=intestinal morphology en-keyword=vitamin D kn-keyword=vitamin D en-keyword=mouse model kn-keyword=mouse model END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=11 article-no= start-page=19516 end-page=19529 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=Structural Design of Litz Wires for Reducing AC Transport Current Loss Using an Equivalent Circuit Model Considering the Path of All Strands en-subtitle= kn-subtitle= en-abstract= kn-abstract=Litz wires are generally fabricated based on the proprietary know-how of wire manufacturers. Therefore, the design guidelines for the conductor structure of low-loss Litz wires have not been clearly established. In this study, we investigated the effect of differences in the conductor structure on the AC resistance using the equivalent circuit model considering the path of all strands. Moreover, we proposed design guidelines for the conductor structure of Litz wires to reduce AC resistance originating from strand paths. Furthermore, we prototyped Litz wires according to the proposed design guidelines and compared the AC resistance of the proposed Litz wires with that of commercial Litz wires. As a result, the AC resistance of the prototyped Litz wires according to the proposed design guidelines was reduced compared to that of the commercial Litz wires. Moreover, the quality factor of the spiral coil using the proposed Litz wire was higher than that using the commercial Litz wire. From the above results, we experimentally clarified that the proposed design guidelines for the conductor structure of Litz wires are effective in reducing the AC resistance originating from strand paths. en-copyright= kn-copyright= en-aut-name=InoueRyota en-aut-sei=Inoue en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UedaHiroshi en-aut-sei=Ueda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimSeokBeom en-aut-sei=Kim en-aut-mei=SeokBeom kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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= en-keyword=AC resistance kn-keyword=AC resistance en-keyword=copper loss kn-keyword=copper loss en-keyword=equivalent circuit kn-keyword=equivalent circuit en-keyword=Litz wire kn-keyword=Litz wire en-keyword=spiral coil kn-keyword=spiral coil END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=5 article-no= start-page=764 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=The New Era of Intraperitoneal Carboplatin in Ovarian Cancer: From Biological Rationale to Clinical Implementation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Epithelial ovarian cancer is predominantly characterized by peritoneal dissemination, providing a strong biological rationale for intraperitoneal (IP) chemotherapy. Although IP cisplatin-based regimens have demonstrated substantial survival benefits in pivotal randomized trials, toxicity and catheter-related complications limit their widespread adoption. IP carboplatin has emerged as a pragmatic alternative with improved tolerability while preserving its pharmacokinetic advantages. This review summarizes the biological and pharmacological rationale for IP carboplatin and critically examines the clinical evidence, with a particular emphasis on the Intraperitoneal Carboplatin for Ovarian Cancer (iPocc) trial and its divergence from Gynecologic Oncology Group (GOG)-252. We further discuss the potential applicability of IP carboplatin beyond the traditional setting of minimal residual disease, including patients undergoing neoadjuvant chemotherapy and interval debulking surgery, as well as its possible use in the contemporary era of maintenance therapy. Collectively, the accumulated evidence supports renewed consideration of IP carboplatin as a versatile component in modern ovarian cancer management. en-copyright= kn-copyright= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujikawaAtsushi en-aut-sei=Fujikawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaYui en-aut-sei=Tanaka en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniokaMomoko en-aut-sei=Tanioka en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImataniRyoko en-aut-sei=Imatani en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TaniYoshinori en-aut-sei=Tani en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugiharaHanako en-aut-sei=Sugihara en-aut-mei=Hanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=MatsuokaHirofumi en-aut-sei=Matsuoka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IdaNaoyuki en-aut-sei=Ida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HaragaJunko en-aut-sei=Haraga en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OgawaChikako en-aut-sei=Ogawa en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=ovarian cancer kn-keyword=ovarian cancer en-keyword=intraperitoneal chemotherapy kn-keyword=intraperitoneal chemotherapy en-keyword=carboplatin kn-keyword=carboplatin en-keyword=dose-dense TC therapy kn-keyword=dose-dense TC therapy en-keyword=homologous recombination deficiency kn-keyword=homologous recombination deficiency en-keyword=PARP inhibitor kn-keyword=PARP inhibitor en-keyword=neoadjuvant chemotherapy kn-keyword=neoadjuvant chemotherapy END start-ver=1.4 cd-journal=joma no-vol=91 cd-vols= no-issue= article-no= start-page=103582 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=Does ESG performance enhance investment efficiency and firm performance? Evidence from Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study examines the association between investment sensitivity to growth opportunities, firm performance, and environmental, social, and governance (ESG) performance in Japanese listed firms. To determine whether ESG performance is associated with a firm’s investment sensitivity to growth opportunities rather than directly increasing investment levels, panel data covering the period from 2002 to 2023 and an investment-Q sensitivity framework are employed. To evaluate robustness and reduce endogeneity issues, high-dimensional fixed effects (HDFE), the System Generalized Method of Moments (GMM), and a difference-in-differences (DID) design based on Japan’s post-2015 governance and disclosure environment are added to the baseline fixed-effects estimations. The findings show a positive association between investment-Q sensitivity and ESG performance, indicating a conditional association wherein firms with higher ESG performance are more receptive to expansion prospects. The findings, however, contradict the hypothesis that ESG performance and investment intensity are consistently associated. Stricter identification techniques diminish positive baseline associations, demonstrating sensitivity to model specification and cross-sectional firm variations. As a result, firm performance results are mixed. Governance-related factors are comparatively more consistently associated with investment outcomes across all ESG components. By focusing on ESG performance and capital allocation behavior under various economic scenarios rather than on whether ESG generally enhances firm outcomes, this study expands the ESG literature. The results imply that ESG serves more as a governance and information mechanism associated with investment sensitivity than as a reliable indicator of firm performance or investment efficiency. en-copyright= kn-copyright= en-aut-name=NazirYusra en-aut-sei=Nazir en-aut-mei=Yusra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=CaiXiaojing en-aut-sei=Cai en-aut-mei=Xiaojing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TennojiyaTatsumasa en-aut-sei=Tennojiya en-aut-mei=Tatsumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Humanities and Social Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Humanities and Social Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Humanities and Social Sciences, Okayama University kn-affil= en-keyword=ESG performance kn-keyword=ESG performance en-keyword=Investment efficiency kn-keyword=Investment efficiency en-keyword=Firm performance kn-keyword=Firm performance en-keyword=Return on assets kn-keyword=Return on assets en-keyword=Asset turnover kn-keyword=Asset turnover en-keyword=Corporate sustainability kn-keyword=Corporate sustainability en-keyword=Japanese firms kn-keyword=Japanese firms END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=8 article-no= start-page=e91242 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250829 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy of Ibuprofen Gargle for Oral Lichen Planus: A Single-Center, Placebo-Controlled, Double-Blind, Randomized Crossover Study Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: Oral lichen planus (OLP) is a chronic, refractory type of stomatitis characterized by abnormal keratinization and often accompanied by pain. The best treatment for OLP, particularly for pain management, remains unclear. This study focuses on the short-term efficacy of ibuprofen gargle for pain relief in patients with OLP.
Methods: In this crossover study, 24 patients with painful OLP were enrolled. One group received an ibuprofen gargle (0.6%) on days one and three to five and a placebo on day two. The other group received a placebo on day one and ibuprofen on days two to five. The primary outcome was the change in pain level, measured by a Visual Analogue Scale (VAS) before and after gargling on days one and two. Additionally, changes in each domain of the Patient-Reported Oral Mucositis Symptom (PROMS) scale were evaluated from days one to five.
Results: There was no significant difference in the degree of reduction in pain VAS values between the ibuprofen and placebo groups before and five and 15 minutes after use of the gargle. However, the PROMS scale showed a significant reduction in dietary restrictions (p = 0.032) in favor of the ibuprofen gargle compared to baseline.
Conclusion: Ibuprofen gargle may help alleviate dietary restrictions associated with oral intake in patients with OLP who experience pain.
Trial registration: This study was registered with the Japan Registry of Clinical Trials (jRCT) (jRCTs051220009). en-copyright= kn-copyright= en-aut-name=KakeiYasumasa en-aut-sei=Kakei en-aut-mei=Yasumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=IoroiTakeshi en-aut-sei=Ioroi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KashinMasahiko en-aut-sei=Kashin en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiMasaki en-aut-sei=Kobayashi en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriokaAsami en-aut-sei=Morioka en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=HasegawaTakumi en-aut-sei=Hasegawa en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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= en-aut-name=AkashiMasaya en-aut-sei=Akashi en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Pharmacy, Kobe University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Pharmacy, Kobe University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Oral and Maxillofacial Surgery, Shin-suma General Hospital kn-affil= affil-num=6 en-affil=Pharmacy, Kobe University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Integrated Clinical and Basic Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Pharmacy, Kobe University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine kn-affil= en-keyword=crossover study kn-keyword=crossover study en-keyword=ibuprofen kn-keyword=ibuprofen en-keyword=mouthwash kn-keyword=mouthwash en-keyword=oral lichen planus kn-keyword=oral lichen planus en-keyword=pain kn-keyword=pain END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=7 article-no= start-page=1527 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260713 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Upregulation of the Outer Membrane Protein OmpV and Its Role in Polymyxin B Stress Adaptation in Vibrio mimicus en-subtitle= kn-subtitle= en-abstract= kn-abstract=OmpV is an outer membrane protein found in a variety of Gram-negative bacteria. In this study, we demonstrated that V. mimicus strain CS-66, isolated from a patient with diarrhea, was resistant to polymyxin B (PL-B) and colistin (CL) but susceptible to chloramphenicol and ciprofloxacin. When strain CS-66 was cultured in Luria?Bertani broth containing a sub-minimal inhibitory concentration of each antibiotic used for the susceptibility tests, ompV expression as assayed by reverse transcription-qPCR, significantly increased regardless of the antibiotic tested. In contrast, cell aggregation during the early log phase was observed only when the strain was grown in the broth supplemented with PL-B or CL. A space-filling model of V. mimicus OmpV was generated. The model showed that, although OmpV adopted a β-barrel conformation, it had closed top and bottom ends and possessed a lateral cavity. Structural analysis further indicated that the interior of this lateral cavity was negatively charged and sufficiently large to accommodate PL-B. These results suggest that V. mimicus may adapt to PL-B stress through physical sequestration within the negatively charged cavity of OmpV. en-copyright= kn-copyright= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnoderaYuta en-aut-sei=Onodera en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AnnoiShunki en-aut-sei=Annoi en-aut-mei=Shunki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MuzemboBasilua Andre en-aut-sei=Muzembo en-aut-mei=Basilua Andre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Research Center for Intestinal Health Science, Okayama University kn-affil= affil-num=5 en-affil=Research Institute of Nursing Care for People and Community, University of Hyogo kn-affil= en-keyword=Vibrio mimicus kn-keyword=Vibrio mimicus en-keyword=polymyxin B kn-keyword=polymyxin B en-keyword=OmpV kn-keyword=OmpV en-keyword=β-barrel protein kn-keyword=β-barrel protein en-keyword=antibiotic sequestration kn-keyword=antibiotic sequestration END start-ver=1.4 cd-journal=joma no-vol=127 cd-vols= no-issue= article-no= start-page=111090 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=Outcome-aware and interpretable subtyping of chronic kidney disease: an analysis of the FROM-J study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chronic kidney disease (CKD) affects approximately 10% of the global population and exhibits substantial heterogeneity in disease progression and clinical outcomes. Despite ongoing efforts to develop new therapeutic strategies, the number of patients progressing to end-stage kidney disease (ESKD) and the incidence of cardiovascular disease (CVD) continue to rise. Although severity classification systems for CKD are well established and refined, they remain insufficient to capture prognostically relevant patient subtypes. In this study, we developed an outcome-aware and interpretable clustering framework for CKD subtyping using data from the FROM-J cohort with prognostic follow-up. A supervised XGBoost model was first trained to predict a ? 30% decline in estimated glomerular filtration rate (eGFR), a surrogate marker of CKD progression. SHAP (SHapley Additive exPlanations) values derived from this model were then used to quantify outcome-relevant feature contributions. Based on these feature attributions, a similarity graph was constructed, and spectral clustering was performed to identify patient subtypes driven by prognostic relevance. The proposed framework identified four CKD subtypes with distinct baseline clinical characteristics and significantly different risks of renal replacement therapy (RRT) and cardiovascular disease (CVD) events. Serum albumin, blood urea nitrogen (BUN), and smoking status consistently emerged as key features defining subtype structure and prognosis. Robust risk stratification was preserved even when clustering was restricted to these three routinely measured variables. Overall, our findings demonstrate that integrating outcome-driven feature attribution into clustering enables interpretable and clinically relevant CKD subtyping, providing a practical approach for characterizing disease heterogeneity and supporting risk stratification and personalized management. en-copyright= kn-copyright= en-aut-name=ShiTianyi en-aut-sei=Shi en-aut-mei=Tianyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YeXiucai en-aut-sei=Ye en-aut-mei=Xiucai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=XiWenyu en-aut-sei=Xi en-aut-mei=Wenyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImakuraAkira en-aut-sei=Imakura en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaseKaori en-aut-sei=Mase en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsunodaRyoya en-aut-sei=Tsunoda en-aut-mei=Ryoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaitoChie en-aut-sei=Saito en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatoAkihiko en-aut-sei=Kato en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=MaruyamaShoichi en-aut-sei=Maruyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WadaTakashi en-aut-sei=Wada en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 ORCID= en-aut-name=SakuraiTetsuya en-aut-sei=Sakurai en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Computer Science, University of Tsukuba kn-affil= affil-num=2 en-affil=Department of Computer Science, University of Tsukuba kn-affil= affil-num=3 en-affil=Department of Computer Science, University of Tsukuba kn-affil= affil-num=4 en-affil=Department of Computer Science, University of Tsukuba kn-affil= affil-num=5 en-affil=Department of Nephrology, Faculty of Medicine, University of Tsukuba kn-affil= affil-num=6 en-affil=Department of Nephrology, Faculty of Medicine, University of Tsukuba kn-affil= affil-num=7 en-affil=Department of Nephrology, Faculty of Medicine, University of Tsukuba kn-affil= affil-num=8 en-affil=Blood Purification Unit, Hamamatsu University School of Medicine 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, Nagoya University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Nephrology and Rheumatology, Kanazawa University kn-affil= affil-num=12 en-affil=Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=13 en-affil=Department of Nephrology, Faculty of Medicine, University of Tsukuba kn-affil= affil-num=14 en-affil=Department of Computer Science, University of Tsukuba kn-affil= en-keyword=Chronic kidney disease kn-keyword=Chronic kidney disease en-keyword=Outcome-aware clustering kn-keyword=Outcome-aware clustering en-keyword=Interpretable machine learning kn-keyword=Interpretable machine learning en-keyword=Risk stratification kn-keyword=Risk stratification en-keyword=Disease progression kn-keyword=Disease progression END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue= article-no= start-page=1874501 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260723 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High horizontal force and lateral force transmission induced by the twist of the Achilles tendon en-subtitle= kn-subtitle= en-abstract= kn-abstract=The Achilles tendon?the largest and strongest of the many tendons in the human body?consists of subtendons arising from each head of the triceps surae. These subtendons run helically and intertwine to form a twisted three-dimensional structure. More than a century has passed since the twisted structure of the Achilles tendon was first described, and numerous studies have investigated its functional morphology. However, it remains unclear how the presence or degree of twist affects the mechanical function of the lower limbs. Here, using finite element models of the Achilles tendon with and without twist, we show that the presence and degree of twist can modulate the forces transmitted from muscle to skeleton in a complex manner. In contrast to the model without twist, the twisted models clearly exhibit anterolaterally directed horizontal forces at the distal end under a simple proximal tensile load. The lateral and anterior components reach approximately 101 N and 63 N, respectively. Furthermore, the twisted structure induces inter-subtendon force transmission, and the magnitude of the transmitted force increases with increasing degree of twist. These results indicate that the uniaxial contractile force generated by the triceps surae is transformed into triaxial forces by the twisted Achilles tendon and is redistributed in a complex three-dimensional manner through inter-subtendon interactions. en-copyright= kn-copyright= en-aut-name=EnomotoShota en-aut-sei=Enomoto en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoKohta en-aut-sei=Ito en-aut-mei=Kohta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=2 en-affil=Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= en-keyword=computer aided engineering kn-keyword=computer aided engineering en-keyword=finite element analysis kn-keyword=finite element analysis en-keyword=modeling kn-keyword=modeling en-keyword=morphology kn-keyword=morphology en-keyword=subtendons kn-keyword=subtendons END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260717 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tripartite Interaction Between Penicillium pinophilum-Host Plants and CMV-Y: A Model for Endophyte-Mediated Viral Biocontrol en-subtitle= kn-subtitle= en-abstract= kn-abstract=Plant-fungus-virus tripartite interactions represent complex ecological systems in which mutualistic endophytes can influence host physiology, yet the molecular basis of endophyte-mediated defence remains poorly understood. Here, we demonstrate that the endophytic fungus Penicillium pinophilum EU0013 suppresses the yellow strain of cucumber mosaic virus (CMV-Y) in Solanum lycopersicum and Nicotiana benthamiana. CMV-Y infection induced pronounced oxidative and hormonal perturbations, which were mitigated by P. pinophilum colonisation. Endophyte-associated plants exhibited early accumulation of jasmonate intermediates, consistent with the activation of jasmonate signalling. This response promoted the degradation of jasmonate-ZIM-domain proteins and release of core JA-responsive transcription factors. Virus-induced gene silencing identified MYC2 as a key regulator required for endophyte-mediated antiviral protection, with WRKY17 contributing to defence modulation. In parallel, transcriptome analysis revealed the upregulation of a Dicer-like gene, indicating enhanced engagement of RNA silencing, a primary antiviral mechanism targeting viral RNA. This coordinated activation occurred alongside significant induction of pathogenesis-related proteins, particularly PR9, and improved control of reactive oxygen species. Salicylic acid-responsive defences showed a host-modulated pattern, with PR1 induced by CMV and PR2/PR5 preferentially enhanced in endophyte-associated plants. Collectively, these findings demonstrate that P. pinophilum enhances antiviral immunity through coordinated defence integration pathways, providing a framework for endophyte-based viral disease management. en-copyright= kn-copyright= en-aut-name=IbiangSarah R. en-aut-sei=Ibiang en-aut-mei=Sarah R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GalisIvan en-aut-sei=Galis en-aut-mei=Ivan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Group of Plant-Microbe Interactions, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Group of Plant-Insect Interactions, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Group of Plant-Microbe Interactions, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Group of Plant-Microbe Interactions, Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=cucumber mosaic virus kn-keyword=cucumber mosaic virus en-keyword=endophyte‐mediated resistance kn-keyword=endophyte‐mediated resistance en-keyword=jasmonate signalling kn-keyword=jasmonate signalling en-keyword=pathogenesis‐related proteins kn-keyword=pathogenesis‐related proteins en-keyword=solanaceae kn-keyword=solanaceae en-keyword=tripartite interaction kn-keyword=tripartite interaction END start-ver=1.4 cd-journal=joma no-vol=429 cd-vols= no-issue= article-no= start-page=140693 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2027 dt-pub=202702 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mechanism of Enhanced Heat Release in Spray Combustion of a Methanol?DME Blended Fuel en-subtitle= kn-subtitle= en-abstract= kn-abstract=This paper investigates the spray combustion characteristics of a methanol?DME blended fuel with a DME mole fraction of 0.57 in a constant volume vessel. The rate of heat release (ROHR) was evaluated using pressure-based heat release analysis. The results show that the methanol?DME blended fuel requires a longer injection duration due to the lower LHV (lower heating value), but it exhibits a shorter combustion duration than conventional diesel fuel, together with a higher ROHR normalized by the injection LHV rate and a shorter afterburning duration. To elucidate the relationship between the spray combustion processes and the ROHR characteristics, the spray flame was visualized using schlieren and OH chemiluminescence imaging techniques. In addition, a one-dimensional simulation based on a diesel jet model was conducted to evaluate the distributions of the equivalence ratio. These analyses reveal that the lower theoretical air?fuel ratio, attributed to the oxygenated nature of the methanol?DME blended fuel, reduces the equivalence ratio within the spray, promoting earlier formation of near-stoichiometric mixtures. As a result, the ROHR reaches and sustains its maximum earlier during mixing-controlled combustion, and fuel consumption is enhanced during afterburning. en-copyright= kn-copyright= en-aut-name=KobashiYoshimitsu en-aut-sei=Kobashi en-aut-mei=Yoshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MakinoShodai en-aut-sei=Makino en-aut-mei=Shodai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NambaMasakuni en-aut-sei=Namba en-aut-mei=Masakuni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawaharaNobuyuki en-aut-sei=Kawahara en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AsakaKatsuyoshi en-aut-sei=Asaka en-aut-mei=Katsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiKazuyuki en-aut-sei=Kobayashi en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Technical Management Division, Carbon Neutral Technology Department, DAIHATSU INFINEARTH MFG. CO., LTD. kn-affil= affil-num=6 en-affil=Technical Management Division, Carbon Neutral Technology Department, DAIHATSU INFINEARTH MFG. CO., LTD. kn-affil= en-keyword=Diesel Engine kn-keyword=Diesel Engine en-keyword=Methanol kn-keyword=Methanol en-keyword=DME kn-keyword=DME en-keyword=Mixing-controlled combustion kn-keyword=Mixing-controlled combustion en-keyword=Oxygenated fuel kn-keyword=Oxygenated fuel 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=17 cd-vols= no-issue= article-no= start-page=1875734 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Quantitative resistance to Rhizoctonia solani AG-4 develops independently in leaves and roots of Brachypodium distachyon en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rhizoctonia solani is a soil-borne phytopathogen with a broad host range, classified into multiple anastomosis groups (AGs). While the rice sheath blight pathogen AG-1 IA is well-studied, defense mechanisms against AG-4, which infects diverse monocots and dicots, remain unclear. Here, we screened 153 Brachypodium distachyon accessions for resistance to AG-4 HG-I+II using both leaf and soil inoculation assays. The accessions exhibited a quantitative resistance spectrum in both assays. Some accessions were resistant to both methods, while others showed resistance in only one, indicating that leaf and root defenses operate independently. Unlike the salicylic acid (SA)-dependent resistance observed in several accessions against AG-1 IA, AG-4 leaf resistance appears to be largely SA-independent. Among 22 resistant accessions, only eight induced the SA marker BdWRKY38, whereas twelve induced the jasmonic acid (JA) marker BdAOS. Additionally, resistance in Bd3?1 was unaffected by expression of the SA hydroxylase NahG. These results are consistent with previous findings that exogenous application of SA, JA, or ethylene fails to confer AG-4 resistance. Instead, most AG-4-resistant accessions showed common upregulation of cell wall biosynthesis-related genes following leaf infection, suggesting that cell wall fortification may contribute to defense against AG-4. These findings establish B. distachyon as a valuable model for dissecting resistance mechanisms against R. solani AG-4. en-copyright= kn-copyright= en-aut-name=FernandaRozi en-aut-sei=Fernanda en-aut-mei=Rozi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MahadevanNiranjan en-aut-sei=Mahadevan en-aut-mei=Niranjan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KohnoNatsuka en-aut-sei=Kohno en-aut-mei=Natsuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagaoReiko en-aut-sei=Nagao en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeMegumi en-aut-sei=Watanabe en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakataNanami en-aut-sei=Sakata en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuiHidenori en-aut-sei=Matsui en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ToyodaKazuhiro en-aut-sei=Toyoda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IchinoseYuki en-aut-sei=Ichinose en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KouzaiYusuke en-aut-sei=Kouzai en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MochidaKeiichi en-aut-sei=Mochida en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NoutoshiYoshiteru en-aut-sei=Noutoshi en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=School of Agriculture, Okayama University kn-affil= affil-num=4 en-affil=School of Agriculture, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Crop Stress Management Group, Division of Plant Molecular Regulation Research, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO) kn-affil= affil-num=11 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=12 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Brachypodium distachyon kn-keyword=Brachypodium distachyon en-keyword=cell wall fortification kn-keyword=cell wall fortification en-keyword=phytohormone kn-keyword=phytohormone en-keyword=quantitative resistance kn-keyword=quantitative resistance en-keyword=Rhizoctonia solani kn-keyword=Rhizoctonia solani en-keyword=root infection kn-keyword=root infection END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3 article-no= start-page=400 end-page=408 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202607 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Outcomes following the discontinuation of biologic therapy in patients with severe asthma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Biologic therapies are pivotal in managing severe asthma. Despite their efficacy, some patients discontinue biologics, with varying outcomes. Predictors of successful versus unsuccessful discontinuation remain poorly defined. This study aimed to identify clinical factors associated with post-discontinuation outcomes in a real-world practice.
Methods: This retrospective cohort included adults with severe asthma who had received biologics for at least 12 months and subsequently discontinued therapy for a minimum of three consecutive months. We assessed the effects of baseline blood eosinophilia (?300 cells/μL), residual sputum symptoms during biologic therapy, treatment responsiveness, biologic class, and discontinuation reasons on post-discontinuation asthma exacerbation rates using multivariable Cox models.
Results: A total of 118 patients were analyzed. The Kaplan?Meier analysis estimated a 65 % exacerbation-free probability at 12 months after discontinuation. Factors associated with successful discontinuation included a robust clinical response and absence of exacerbations before cessation. Conversely, baseline eosinophilia, residual sputum symptoms during biologics, and discontinuation due to inadequate therapeutic response or financial burden were associated with post-discontinuation exacerbations. In class-stratified restricted models, persistent sputum remained significantly associated with post-discontinuation exacerbations after stopping anti-IL-5 therapies, while baseline eosinophilia was associated with post-discontinuation exacerbations after stopping anti-IgE or anti-IL-4Rα. Among patients with sputum symptoms or poor-response discontinuation, the overall frequency of exacerbations declined after discontinuation.
Conclusions: Baseline eosinophilia, persistent sputum during therapy, and discontinuation prompted by poor response or cost may serve as risk factors for post-discontinuation exacerbations; however, risk is phenotype- and class-dependent. Careful patient selection and monitoring are essential when considering the discontinuation of biologic treatment. en-copyright= kn-copyright= en-aut-name=NagasakiTadao en-aut-sei=Nagasaki en-aut-mei=Tadao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoHisako en-aut-sei=Matsumoto en-aut-mei=Hisako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IwanagaTakashi en-aut-sei=Iwanaga en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsunagaKazuto en-aut-sei=Matsunaga en-aut-mei=Kazuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SekiyaKiyoshi en-aut-sei=Sekiya en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaradaTomoya en-aut-sei=Harada en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakuraiShogo en-aut-sei=Sakurai en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaradaNorihiro en-aut-sei=Harada en-aut-mei=Norihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KoyaToshiyuki en-aut-sei=Koya en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukunagaKoichi en-aut-sei=Fukunaga en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KanekoTakeshi en-aut-sei=Kaneko en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AsaiKazuhisa en-aut-sei=Asai en-aut-mei=Kazuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KomaseYuko en-aut-sei=Komase en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=GonYasuhiro en-aut-sei=Gon en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaAkihiko en-aut-sei=Tanaka en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SagaraHironori en-aut-sei=Sagara en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SunadomeHironobu en-aut-sei=Sunadome en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NaganoTatsuya en-aut-sei=Nagano en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=NakamuraYoichi en-aut-sei=Nakamura en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=NiimiAkio en-aut-sei=Niimi en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HattoriNoboru en-aut-sei=Hattori en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HajiroTakashi en-aut-sei=Hajiro en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FujimotoHajime en-aut-sei=Fujimoto en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HojoMasayuki en-aut-sei=Hojo en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=MiyaharaNobuaki en-aut-sei=Miyahara en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=YamaguchiMasafumi en-aut-sei=Yamaguchi en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TsujiKimiko en-aut-sei=Tsuji en-aut-mei=Kimiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=SanoAkiko en-aut-sei=Sano en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=HaraguchiRyuta en-aut-sei=Haraguchi en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SanoHiroyuki en-aut-sei=Sano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=MurakiMasato en-aut-sei=Muraki en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=TohdaYuji en-aut-sei=Tohda en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University kn-affil= affil-num=5 en-affil=Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital kn-affil= affil-num=6 en-affil=Department of Multidisciplinary Internal Medicine, Division of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori University kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Shizuoka General Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=10 en-affil=Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine kn-affil= affil-num=11 en-affil=Department of Pulmonology, Yokohama City University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, St.Marianna University School of Medicine, Yokohama Seibu Hospital kn-affil= affil-num=14 en-affil=Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine kn-affil= affil-num=15 en-affil=Department of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University, School of Medicine kn-affil= affil-num=16 en-affil=Department of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University, School of Medicine kn-affil= affil-num=17 en-affil=Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University kn-affil= affil-num=18 en-affil=Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Medical Center for Allergic and Immune Diseases, Yokohama City Minato Red Cross Hospital kn-affil= affil-num=20 en-affil=Department of Respiratory Medicine, Allergy, and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=21 en-affil=Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University kn-affil= affil-num=22 en-affil=Department of Respiratory Medicine, Tenri Hospital kn-affil= affil-num=23 en-affil=Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine kn-affil= affil-num=24 en-affil=Division of Respiratory Medicine, National Center for Global Health and Medicine kn-affil= affil-num=25 en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=26 en-affil=Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science kn-affil= affil-num=27 en-affil=Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University kn-affil= affil-num=28 en-affil=Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine kn-affil= affil-num=29 en-affil=Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine kn-affil= affil-num=30 en-affil=Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine kn-affil= affil-num=31 en-affil=Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital kn-affil= affil-num=32 en-affil=Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine kn-affil= en-keyword=Adult asthma kn-keyword=Adult asthma en-keyword=Biologics kn-keyword=Biologics en-keyword=Discontinuation kn-keyword=Discontinuation en-keyword=Exacerbation kn-keyword=Exacerbation en-keyword=Severe asthma kn-keyword=Severe asthma END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=1 article-no= start-page=35 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oral health care during pregnancy to prevent preterm birth and low birth weight: study protocol for a randomized controlled trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Periodontal disease during pregnancy has been associated with an increased risk of preterm birth (PTB) and low birth weight (LBW). However, most previous interventional studies have reported that scaling and root planing (SRP), a form of basic periodontal treatment, is insufficient to effectively prevent PTB and LBW. Recent systematic reviews and meta-analyses suggest that combining SRP with routine use of chlorhexidine gluconate (CHG) mouthwash may reduce the risk of these adverse birth outcomes by approximately half. This study will be among the first randomized controlled trials (RCTs) to evaluate the potential synergistic effects of this combined approach on improving birth outcomes.
Methods This multi-center, three-arm RCT will be conducted at two hospitals in Dhaka and Bogura, Bangladesh, between April 2025 and September 2026. A total of 480 pregnant women less than 20 weeks’ gestation attending antenatal checkups will be recruited. Participants diagnosed with periodontal disease will be randomly assigned to either an intervention group or a positive control group. Participants without periodontal disease will be assigned to a negative control group. The intervention consists of SRP combined with continued use of CHG mouthwash throughout pregnancy. The primary outcome will be the rate of PTB. Secondary outcomes include the birth weight of the newborn baby, maternal periodontal status, and oral health-related quality of life (OHRQoL). Effectiveness will be assessed by comparing outcomes across the study groups.
Discussion The oral health intervention is expected to improve both birth outcomes and maternal oral health. Demonstrating its effectiveness in a real-world setting may support the integration of oral health care into broader maternal, neonatal, and child health strategies, particularly in resource-limited settings.
Trial registration UMIN Clinical Trials Registry. UMIN000057519. Registered on April 4, 2025. https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000065719. en-copyright= kn-copyright= en-aut-name=YasuokaJunko en-aut-sei=Yasuoka en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkadaShunsuke en-aut-sei=Okada en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AlamProdhan MD Rubayet en-aut-sei=Alam en-aut-mei=Prodhan MD Rubayet kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShibanumaAkira en-aut-sei=Shibanuma en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NanishiKeiko en-aut-sei=Nanishi en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoYoko en-aut-sei=Sato en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HossainMd. Zahid en-aut-sei=Hossain en-aut-mei=Md. Zahid kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AmanMusfiqa en-aut-sei=Aman en-aut-mei=Musfiqa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KarimFahmida en-aut-sei=Karim en-aut-mei=Fahmida kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=RaziaSultana en-aut-sei=Razia en-aut-mei=Sultana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=RezwanaRifat en-aut-sei=Rezwana en-aut-mei=Rifat kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=RahmanMd Mahmudur en-aut-sei=Rahman en-aut-mei=Md Mahmudur kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Jahan KhanNusrat en-aut-sei=Jahan Khan en-aut-mei=Nusrat kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakashimaNaoki en-aut-sei=Nakashima en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IslamRafiqul en-aut-sei=Islam en-aut-mei=Rafiqul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KikuchiKimiyo en-aut-sei=Kikuchi en-aut-mei=Kimiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Division of Global Health Sciences, Graduate School of Public Health, St. Luke’s International University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Medical Development Field, Okayama University kn-affil= affil-num=4 en-affil=Department of Orthodontics, Dental Unit, TMSS Medical College & Rafatullah Community Hospital kn-affil= affil-num=5 en-affil=Department of Community and Global Health, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Office of International Academic Affairs, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=8 en-affil=Department of Periodontology and Oral Pathology, Holy Family Red Crescent Medical College Hospital kn-affil= affil-num=9 en-affil=Department of Periodontology, Dental Unit, TMSS Medical College & Rafatullah Community Hospital kn-affil= affil-num=10 en-affil=Department of Obstetrics & Gynecology, Holy Family Red Crescent Medical College Hospital kn-affil= affil-num=11 en-affil=Department of Obstetrics & Gynecology, TMSS Medical College & Rafatullah Community Hospital kn-affil= affil-num=12 en-affil=Department of Molecular and Cellular Biochemistry, Division of Oral Health, Brain Health and Total Health, Faculty of Dental Science, Kyushu University kn-affil= affil-num=13 en-affil=Global Communication Center, Grameen Communications kn-affil= affil-num=14 en-affil=Global Communication Center, Grameen Communications kn-affil= affil-num=15 en-affil=Department of Medical Informatics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=16 en-affil=Division of Healthcare Digital Transformation, Kyushu University kn-affil= affil-num=17 en-affil=Department of Research Promotion, Institute for Asian and Oceanian Studies, Kyushu University kn-affil= en-keyword=Preterm birth kn-keyword=Preterm birth en-keyword=Low birth weight kn-keyword=Low birth weight en-keyword=Oral health kn-keyword=Oral health en-keyword=Periodontal treatment kn-keyword=Periodontal treatment en-keyword=Chlorhexidine gluconate mouthwash kn-keyword=Chlorhexidine gluconate mouthwash en-keyword=Randomized controlled trial kn-keyword=Randomized controlled trial en-keyword=Bangladesh kn-keyword=Bangladesh END start-ver=1.4 cd-journal=joma no-vol=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? 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=53 cd-vols= no-issue=14 article-no= start-page=e2026GL121981 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260710 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Calcium Solubility of Bridgmanite in Subducted Basalt in Earth's Lower Mantle en-subtitle= kn-subtitle= en-abstract= kn-abstract=The calcium solubility in bridgmanite and the resulting abundance of davemaoite under lower-mantle pressure-temperature conditions have been under debate following a recent report of extensive calcium dissolution in bridgmanite. We experimentally investigated the calcium solubility in bridgmanite in a basaltic composition at pressures up to 125 GPa and temperatures up to 3,520 K. Our experimental data are modeled thermodynamically along the bridgmanite-davemaoite solvus to quantify the calcium solubility in bridgmanite and the davemaoite proportion in basaltic and pyrolitic assemblages along lower mantle geotherms. Our results indicate that bridgmanite hosts only 0.001?0.03 Ca cations per formula unit in the lower mantle, while davemaoite remains as an abundant mineral, accounting for 8 and 25 vol% of pyrolitic and basaltic mineralogical models, respectively, along representative lower-mantle geotherms. Our thermoelastic modeling further indicates that the effect of calcium dissolution on the density and bulk sound velocity of lower-mantle assemblages is negligible. en-copyright= kn-copyright= en-aut-name=ZhangChengwei en-aut-sei=Zhang en-aut-mei=Chengwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshinoTakashi en-aut-sei=Yoshino en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=El GhazaouiElias en-aut-sei=El Ghazaoui en-aut-mei=Elias kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=LiLuo en-aut-sei=Li en-aut-mei=Luo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhangYanyao en-aut-sei=Zhang en-aut-mei=Yanyao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=School of Earth and Environmental Sciences, Seoul National University kn-affil= affil-num=4 en-affil=Center for Advanced Radiation Sources, The University of Chicago kn-affil= affil-num=5 en-affil=Center for Advanced Radiation Sources, The University of Chicago kn-affil= affil-num=6 en-affil=Department of Earth and Planetary Sciences, Jackson School of Geosciences The University of Texas at Austin kn-affil= affil-num=7 en-affil=Earth and Planetary Sciences, Stanford University kn-affil= affil-num=8 en-affil=Department of Earth and Planetary Sciences, Jackson School of Geosciences The University of Texas at Austin kn-affil= END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=1 article-no= start-page=128 end-page=135 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Developing and Implementing a Disaster Prevention Game to Enhance Local Understanding en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study developed and implemented a local disaster prevention sugoroku-style game to address challenges in preserving and transmitting regional knowledge in areas with high population mobility. Many Japanese communities face both natural and social vulnerabilities, and effective disaster education requires linking hazard knowledge with local characteristics. Conducted at Sonan Junior High School in Okayama, the project combined lectures, workshops, and a community engagement event. Students learned about regional topography, land use, and disaster history and used this knowledge to design quizzes, rules, and disaster scenarios for the game. The final sugoroku set included a map-based board, thematic quiz areas, and preparedness item cards, enabling players to predict damage and consider appropriate actions. After creating the game, students shifted from identifying familiar landmarks to describing concrete disaster impacts such as liquefaction or infrastructure collapse. Interaction with local residents further enriched learning through shared experiences. The model proved feasible in terms of time and cost, and its structure is easily adaptable to other regions by incorporating local information. The findings suggest that this participatory, place-based approach enhances imagination, self-efficacy, and intergenerational knowledge transfer, contributing to community-wide disaster preparedness. Future studies will examine long-term educational impacts and broader regional applications. en-copyright= kn-copyright= en-aut-name=ShirokaneMiri en-aut-sei=Shirokane en-aut-mei=Miri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaAiri en-aut-sei=Yamada en-aut-mei=Airi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MisawaRyo en-aut-sei=Misawa en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MattaNobuhisa en-aut-sei=Matta en-aut-mei=Nobuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Okayama University kn-affil= affil-num=3 en-affil=Okayama University kn-affil= affil-num=4 en-affil=Okayama University kn-affil= en-keyword=disaster education kn-keyword=disaster education en-keyword=local disaster knowledge kn-keyword=local disaster knowledge en-keyword=disaster literacy kn-keyword=disaster literacy en-keyword=damage estimation abilities kn-keyword=damage estimation abilities en-keyword=community resilience kn-keyword=community resilience END start-ver=1.4 cd-journal=joma no-vol=42 cd-vols= no-issue=4 article-no= start-page=350 end-page=361 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=Medaka: a novel model for analyzing genome?environment interactions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Medaka is an established vertebrate model system for biological and biomedical research. It possesses unique features that make it particularly suitable for studying genome?environment interactions. Endemic to habitats spanning from 4 to 40°C and varying salinities, it combines broad ecological adaptability with experimental tractability. Its exceptional tolerance to inbreeding enabled the creation of the Medaka Inbred Kiyosu-Karlsruhe panel?80 near-isogenic, fully sequenced lines derived from a single wild population. More than 100 wild-derived, fully sequenced strains, collected throughout East Asia for more than 40 years, show relatively low intra-strain variation (inbreeding coefficient of >0.75) but high inter-strain variability (SNP rates >4%). Advanced quantification methods facilitate genome-wide association studies and quantitative trait locus mapping. The system’s amenability to clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 editing and emerging epigenomic profiling enables causal validation and regulatory-mechanism discovery. Collectively, medaka offers an unparalleled vertebrate framework for integrating genetics, environment, and epigenetics?bridging evolutionary, biomedical, and population-level perspectives. en-copyright= kn-copyright= en-aut-name=NaruseKiyoshi en-aut-sei=Naruse en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LoosliFelix en-aut-sei=Loosli en-aut-mei=Felix kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=BirneyEwan en-aut-sei=Birney en-aut-mei=Ewan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WittbrodtJoachim en-aut-sei=Wittbrodt en-aut-mei=Joachim kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Laboratory of Bioresources, National Institute for Basic Biology kn-affil= affil-num=2 en-affil=Institute of Biological and Chemical Systems, Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology kn-affil= affil-num=3 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=4 en-affil=European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI) kn-affil= affil-num=5 en-affil=Centre for Organismal Studies (COS), Heidelberg University kn-affil= en-keyword=medaka kn-keyword=medaka en-keyword=population genetics resource kn-keyword=population genetics resource en-keyword=wild-derived strains kn-keyword=wild-derived strains en-keyword=GWAS kn-keyword=GWAS en-keyword=QTL mapping kn-keyword=QTL mapping en-keyword=genome?environment interactions kn-keyword=genome?environment interactions END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=9 article-no= start-page=e045149 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Insomnia and the Risk of Atrial Fibrillation: A Nationwide, Real‐World Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Insomnia is one of the most prevalent diseases observed in clinical practice, contributing to increased death and a range of chronic diseases. While numerous studies have explored the relationship between insomnia and cardiovascular disease, research on its association with atrial fibrillation (AF) remains limited. This study aimed to investigate the association between insomnia and incident AF in the general population by comprehensive, nationwide, real‐world data in Japan.
Methods: A total of 1?780?764 individuals without prior cardiovascular disease including AF from the DeSC database were included between April 2014 and August 2023. Insomnia was defined by International Classification of Diseases, Tenth Revision (ICD‐10) codes (F510, G470) before the baseline health checkup. The primary outcome was incident AF (I480?I482 and I489). Cox proportional hazards models were used to estimate hazard ratios of AF according to present insomnia (versus absent).
Results: Insomnia was observed in 216?919 individuals (12.2%), showing a significant association with incident AF after adjusting for potential confounding factors (adjusted hazard ratio, 1.14 [95% CI, 1.10?1.18]). Among subgroups, a similar pattern in the association between insomnia and incident AF was seen, while the association was stronger in younger individuals aged <65?years (versus ?65?years) and women (versus men) (P for interaction=0.01 and 0.03, respectively).
Conclusions: Insomnia was significantly associated with the risk of AF. It highlighted the importance of recognizing insomnia as a risk factor for AF, given its high prevalence in the general population and the substantial impact of AF on quality of life and prognosis. en-copyright= kn-copyright= en-aut-name=MasudaTakuro en-aut-sei=Masuda en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanekoHidehiro en-aut-sei=Kaneko en-aut-mei=Hidehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiYuta en-aut-sei=Suzuki en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TayaSatoshi en-aut-sei=Taya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwasakiKeiichiro en-aut-sei=Iwasaki en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishiiNobuhiro en-aut-sei=Nishii en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkadaAkira en-aut-sei=Okada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujiuKatsuhito en-aut-sei=Fujiu en-aut-mei=Katsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakedaNorifumi en-aut-sei=Takeda en-aut-mei=Norifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MoritaHiroyuki en-aut-sei=Morita en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YasunagaHideo en-aut-sei=Yasunaga en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakedaNorihiko en-aut-sei=Takeda en-aut-mei=Norihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Advanced Cardiology, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of 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 Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, The University of Tokyo kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, The University of Tokyo kn-affil= affil-num=14 en-affil=Department of Cardiovascular Medicine, The University of Tokyo kn-affil= affil-num=15 en-affil=Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo kn-affil= affil-num=16 en-affil=Department of Cardiovascular Medicine, The University of Tokyo kn-affil= affil-num=17 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=atrial fibrillation kn-keyword=atrial fibrillation en-keyword=insomnia kn-keyword=insomnia en-keyword=risk factors kn-keyword=risk factors en-keyword=sleep apnea syndrome kn-keyword=sleep apnea syndrome en-keyword=sleep disorder kn-keyword=sleep disorder END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=13 article-no= start-page=4427 end-page=4438 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260714 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Drivers of temporal improvement in CAR T-cell therapy for large B-cell lymphoma: a Japanese nationwide registry analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Real-world CD19 chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL) is characterized by expanded eligibility and evolving management practices. However, the prognostic impact of these changes remains inconsistent, and the specific drivers of outcomes remain unclear. This study analyzed 913 patients with relapsed/refractory (R/R) LBCL from a Japanese registry and compared the outcomes between 2 calendar periods (2019-2021 vs 2022-2024). The 2022-2024 cohort was older, had more adverse baseline features, and was less pretreated. Treatment patterns have shifted toward higher utilization of second-line therapy, a growing preference for axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel), and improved disease control before infusion. Accordingly, the 2022-2024 cohort achieved a longer progression-free survival (PFS; 6-month PFS, 63.2% vs 55.2%; P = .005), which persisted after adjusting for baseline characteristics using propensity score matching. Multivariable analysis identified second-line therapy, improved preinfusion disease control, and a shift in product selection from tisagenlecleucel to axi-cel or liso-cel as the primary drivers of this improvement. This benefit was pronounced in high-risk populations, including patients with stable or progressive disease at infusion (6-month PFS, 54.6% vs 43.8%; P = .012) and those who were refractory to first-line therapy (6-month PFS, 51.7% vs 40.3%; P = .013). Despite broader use in higher-risk populations and greater axi-cel exposure, 6-month nonrelapse mortality remained low (2.1% vs 1.5%). Real-world outcomes of CD19 CAR T-cell therapy for R/R LBCL have improved, predominantly driven by second-line therapy, enhanced preinfusion disease control, and increased use of more potent CAR T products. en-copyright= kn-copyright= en-aut-name=YagiYu en-aut-sei=Yagi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanemasaYusuke en-aut-sei=Kanemasa en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=5 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=6 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=7 ORCID= en-aut-name=HanajiriRyo en-aut-sei=Hanajiri en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshiharaSatoshi en-aut-sei=Yoshihara en-aut-mei=Satoshi 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=IwakiNoriko en-aut-sei=Iwaki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 ORCID= en-aut-name=MatsukawaToshihiro en-aut-sei=Matsukawa en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 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=17 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=18 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=19 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=20 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=21 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=22 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=23 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=24 ORCID= affil-num=1 en-affil=Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=2 en-affil=Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=3 en-affil=2Department of Hematology, Okayama University Hospital, Okayama, Japan kn-affil= affil-num=4 en-affil=Department of Pediatrics, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Hematology, Kyoto University Hospital kn-affil= affil-num=6 en-affil=Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=7 en-affil=Department of Hematology, Kyoto University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Nagoya University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Hyogo Medical University Hospital kn-affil= affil-num=11 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology, National Cancer Center Hospital kn-affil= affil-num=13 en-affil=Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital kn-affil= affil-num=14 en-affil=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=15 en-affil=Department of Hematology, Hokkaido University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology, Chiba University Hospital kn-affil= affil-num=17 en-affil=Hematology and Hematopoietic Cell Transplantation, Osaka Metropolitan University Hospital kn-affil= affil-num=18 en-affil=Division of Transfusion Medicine, Kanazawa University Hospital kn-affil= affil-num=19 en-affil=Department of Hematology, Institute of Science Tokyo Hospital kn-affil= affil-num=20 en-affil=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=21 en-affil=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=22 en-affil=11Department of Hematology, Hokkaido University Hospital, Sapporo, Japan kn-affil= affil-num=23 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=24 en-affil=Department of Hematology, Oncology, and Cardiovascular Medicine, Kyushu University Hospital kn-affil= 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= cd-vols= no-issue= article-no= start-page=hyag102 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of pre-existing schizophrenia spectrum disorder on the receipt of invasive and systemic therapy for gastric cancer: a multicenter nationwide cohort study in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Patients with schizophrenia spectrum disorders (SSD) experience higher cancer mortality, partly because of later-stage diagnosis and lower rates of recommended treatments. While treatment disparities have been reported across several cancer types, no study has specifically examined stage-appropriate treatment for gastric cancer among patients with SSD.
Methods: We conducted a retrospective cohort study using a nationwide Hospital-Based Cancer Registry linked to administrative data in Japan. Patients who received initial treatment for gastric cancer between 2018 and 2021 were included. Multivariable logistic regression models examined the association between SSD and the receipt of stage-appropriate cancer treatments, adjusting for age, sex, clinical stage, Charlson Comorbidity Index, and Barthel Index.
Results: Among 189?447 patients from 709 hospitals, 1312 had SSD. Patients with SSD were more likely to be diagnosed at advanced stages. In crude analysis, SSD was associated with lower rates of surgical or endoscopic treatment; however, this association was not statistically significant after adjustment (adjusted odds ratio [aOR], 0.90; 95% confidence interval [CI], 0.75?1.08). In contrast, SSD was independently associated with lower rates of postoperative adjuvant chemotherapy for pathological stage II/III disease (aOR, 0.64; 95% CI, 0.45?0.91) and systemic therapy for stage IV disease (aOR, 0.36; 95% CI, 0.28?0.47).
Conclusions: Among patients with gastric cancer, SSD was associated with reduced receipt of systemic therapy but not surgical or endoscopic treatment. Efforts to improve early detection among patients with SSD may be important for reducing treatment disparities, alongside strengthened support for systemic therapy to ensure equitable access to guideline-recommended gastric cancer care. en-copyright= kn-copyright= en-aut-name=KhantMyo Min en-aut-sei=Khant en-aut-mei=Myo Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaYuto en-aut-sei=Yamada en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshiiTaisuke en-aut-sei=Ishii en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeTomone en-aut-sei=Watanabe en-aut-mei=Tomone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukaoTakashi en-aut-sei=Fukao en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujimoriMaiko en-aut-sei=Fujimori en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakayaNaoki en-aut-sei=Nakaya en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawamuraToshihiko en-aut-sei=Kawamura en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukiKoji en-aut-sei=Otsuki en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShimazuTaichi en-aut-sei=Shimazu en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HinotsuShiro en-aut-sei=Hinotsu en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UchitomiYosuke en-aut-sei=Uchitomi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=InagakiMasatoshi en-aut-sei=Inagaki en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Medical Development Field, Okayama University kn-affil= affil-num=3 en-affil=Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=4 en-affil=Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=5 en-affil=Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=6 en-affil=Department of Neuropsychiatry, Medical Development Field, Okayama University kn-affil= affil-num=7 en-affil=Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=8 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=9 en-affil=Department of Medical Informatics, Shimane University Hospital kn-affil= affil-num=10 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=13 en-affil=Department of Biostatistics and Data Management, Sapporo Medical University kn-affil= affil-num=14 en-affil=Department of Cancer Survivorship and Digital Medicine, The Jikei University School of Medicine kn-affil= affil-num=15 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= en-keyword=healthcare disparities kn-keyword=healthcare disparities en-keyword=schizophrenia Spectrum and other psychotic disorders kn-keyword=schizophrenia Spectrum and other psychotic disorders en-keyword=stomach neoplasms kn-keyword=stomach neoplasms 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=16 cd-vols= no-issue=1 article-no= start-page=20445 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Metastatic promoting role of mesenchymal stem cells in oral squamous cell carcinoma revealed by an improved bone marrow chimeric model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mesenchymal stem cells (MSCs) are essential stromal regulators that coordinate tissue repair, angiogenesis, and immune balance. Within tumours, MSCs remodel the microenvironment and influence disease progression, yet their systemic contribution remains unclear due to the limited recovery of functional MSCs in conventional bone marrow transplantation models. Here, we developed an improved bone marrow collection (iBMC) method using enzymatic digestion, which markedly increases MSC yield while preserving their native phenotype. GFP bone marrow chimeric mice generated by iBMC and conventional transplantation displayed comparable hematopoietic reconstitution but differed in MSC abundance, enabling direct analysis of MSC-specific effects under physiological conditions. In mouse models of oral squamous cell carcinoma (OSCC), MSCs profoundly affected tumour development. MSC-deficient tumours exhibited necrosis and infiltration of immature myeloid-derived suppressor cells (MDSCs), whereas MSC-rich tumours showed enhanced vascularisation, adaptive immune infiltration, and stromal remodelling. Notably, lung metastasis occurred only in MSC-rich mice, accompanied by bone marrow?derived endothelial activation and TNF-α?driven inflammation. Pharmacological inhibition of LepR signalling using SHU9119 unexpectedly increased metastasis, underscoring the dual, context-dependent functions of MSCs. These findings establish iBMC as a reproducible and physiologically relevant model to study MSC-mediated regulation of tumour immunity, angiogenesis, and metastasis. en-copyright= kn-copyright= en-aut-name=EainHtoo Shwe en-aut-sei=Eain en-aut-mei=Htoo Shwe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SanouSho en-aut-sei=Sanou en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SoeYamin en-aut-sei=Soe en-aut-mei=Yamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=PiaoTianyan en-aut-sei=Piao en-aut-mei=Tianyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MinZin Zin en-aut-sei=Min en-aut-mei=Zin Zin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= affil-num=11 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= en-keyword=Mesenchymal stem cells (MSCs) kn-keyword=Mesenchymal stem cells (MSCs) en-keyword=Oral squamous cell carcinoma (OSCC) kn-keyword=Oral squamous cell carcinoma (OSCC) en-keyword=Bone marrow transplantation kn-keyword=Bone marrow transplantation en-keyword=Chimeric mouse models kn-keyword=Chimeric mouse models en-keyword=Tumour microenvironment (TME) kn-keyword=Tumour microenvironment (TME) 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=69 cd-vols= no-issue=2 article-no= start-page=128 end-page=131 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=RpoB H481Y Rifampicin Resistance Mutation-Associated Oxidative Stress Sensitivity Reduces the Virulence of Staphylococcus aureus en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this study, we have established a Staphylococcus aureus RpoB H481Y mutant strain and demonstrated that it is sensitive to menadione or hydrogen peroxide-induced oxidative stress and exhibits reduced virulence against a silkworm infection model. Furthermore, the reduced virulence of the RpoB H481Y mutant was abrogated in the presence of N-acetylcysteine, a reactive oxygen species scavenger. These results suggest that oxidative stress sensitivity caused by the RpoB H481Y rifampicin resistance mutation attenuates the virulence of S. aureus. en-copyright= kn-copyright= en-aut-name=KanoTomonori en-aut-sei=Kano en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshikawaKazuya en-aut-sei=Ishikawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ImaiLina en-aut-sei=Imai en-aut-mei=Lina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=KaitoChikara en-aut-sei=Kaito en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=RNA polymerase beta subunit kn-keyword=RNA polymerase beta subunit en-keyword=Staphylococcus aureus kn-keyword=Staphylococcus aureus en-keyword=virulence kn-keyword=virulence END start-ver=1.4 cd-journal=joma no-vol=206 cd-vols= no-issue=10 article-no= start-page=e00307-24 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Overexpression of diglucosyldiacylglycerol synthase leads to daptomycin resistance in Bacillus subtilis en-subtitle= kn-subtitle= en-abstract= kn-abstract=The lipopeptide antibiotic daptomycin exhibits bactericidal activity against Gram-positive bacteria by forming a complex with phosphatidylglycerol (PG) and lipid II in the cell membrane, causing membrane perforation. With the emergence of daptomycin-resistant bacteria, understanding the mechanisms of bacterial resistance to daptomycin has gained great importance. In this study, we aimed to identify the genetic factors contributing to daptomycin resistance in Bacillus subtilis, a model Gram-positive bacterium. Our findings demonstrated that overexpression of ugtP, which encodes diglucosyldiacylglycerol synthase, induces daptomycin resistance in B. subtilis. Specifically, overexpression of ugtP resulted in increased levels of diglucosyldiacylglycerol (Glc2DAG) and decreased levels of acidic phospholipids cardiolipin and PG, as well as the basic phospholipid lysylphosphatidylglycerol. However, ugtP overexpression did not alter the cell surface charge and the susceptibility to the cationic antimicrobial peptide nisin or the cationic surfactant hexadecyltrimethylammonium bromide. Furthermore, by serial passaging in the presence of daptomycin, we obtained daptomycin-resistant mutants carrying ugtP mutations. These mutants showed increased levels of Glc2DAG and a >4-fold increase in the minimum inhibitory concentration of daptomycin. These results suggest that increased Glc2DAG levels, driven by ugtP overexpression, modify the phospholipid composition and confer daptomycin resistance in B. subtilis without altering the cell surface charge of the bacteria. en-copyright= kn-copyright= en-aut-name=YamamotoRyogo en-aut-sei=Yamamoto en-aut-mei=Ryogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshikawaKazuya en-aut-sei=Ishikawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyoshiYusuke en-aut-sei=Miyoshi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=KaitoChikara en-aut-sei=Kaito en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=diglucosyldiacylglycerol kn-keyword=diglucosyldiacylglycerol en-keyword=daptomycin kn-keyword=daptomycin en-keyword=phospholipid kn-keyword=phospholipid END start-ver=1.4 cd-journal=joma no-vol=88 cd-vols= no-issue=10 article-no= start-page=1199 end-page=1202 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240711 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of quercetin as a potential cytoprotector against acetaldehyde using the cultured hepatocyte model with aldehyde dehydrogenase isozyme deficiency en-subtitle= kn-subtitle= en-abstract= kn-abstract=Protective effect of quercetin against acetaldehyde was evaluated using the cultured hepatocyte models with aldehyde dehydrogenase (ALDH) isozyme deficiency (aldh2-kd and aldh1a1-kd). The quercetin-induced cytoprotection against acetaldehyde in the ALDH1A1-deficient mutant (aldh1a1-kd) was weaker than that in the wild type. Furthermore, quercetin did not enhance the ALDH activity in aldh1a1-kd cells, suggesting that ALDH1A1 is involved in quercetin-induced cytoprotection. en-copyright= kn-copyright= en-aut-name=XuYuhang en-aut-sei=Xu en-aut-mei=Yuhang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SawamotoTakeshi en-aut-sei=Sawamoto en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SunRuitong en-aut-sei=Sun en-aut-mei=Ruitong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshikuraAki en-aut-sei=Ishikura en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MunemasaShintaro en-aut-sei=Munemasa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MurataYoshiyuki en-aut-sei=Murata en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumotoAkiko en-aut-sei=Matsumoto en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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, Life, Natural Science and Technology, 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 Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Department of Social and Environmental Medicine, Saga University kn-affil= affil-num=9 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=quercetin kn-keyword=quercetin en-keyword=acetaldehyde kn-keyword=acetaldehyde en-keyword=aldehyde dehydrogenase kn-keyword=aldehyde dehydrogenase en-keyword=cytoprotection kn-keyword=cytoprotection END start-ver=1.4 cd-journal=joma no-vol=114 cd-vols= no-issue=2 article-no= start-page=303 end-page=309 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241009 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Outdoor playing during preschool was associated with a reduced risk of school-age obesity in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim: This study investigated the association between outdoor play habits during preschool and school-age obesity.
Methods: We conducted a longitudinal cohort study of all children born in Japan during 2?weeks in January and July 2001. We defined outdoor play habits at age 2.5?years (third survey) as exposure, while parent-reported height and weight at age 7?years (seventh survey) were defined as overweight and obesity status using the WHO reference. Logistic regression models were used to estimate odds ratios (ORs) for associations between preschool outdoor play habits and school-age obesity, adjusting for parental and child factors.
Results: Of 53?575 children born, 42?812 had data on outdoor play habits at age 2.5?years, with 91% (38?970) having such habits. At age 7?years, 31?743/42?812 (74%) children had height and weight data, with 3249/31?743 (10%) classified as overweight or obesity (BMI SD score??1.0). Outdoor play habits were negatively associated with obesity (adjusted OR 0.85, 95% confidence interval (CI): 0.74?0.97).
Conclusion: Outdoor play habits in early preschool years are associated with a reduced risk of school-age obesity. Parents and caregivers may consider encouraging their children to outdoor play habits at an early age to help prevent obesity later in life. en-copyright= kn-copyright= en-aut-name=TsugeTakahiro en-aut-sei=Tsuge en-aut-mei=Takahiro 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=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=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=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=outdoor play habits kn-keyword=outdoor play habits en-keyword=physical activity kn-keyword=physical activity en-keyword=preschool kn-keyword=preschool en-keyword=school-aged obesity kn-keyword=school-aged obesity en-keyword=socioeconomic status kn-keyword=socioeconomic status 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=226 cd-vols= no-issue= article-no= start-page=105997 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=Costly subjective learning en-subtitle= kn-subtitle= en-abstract= kn-abstract=We examine the behavioral foundation of rational inattention within a menu-choice framework. Unlike previous studies, our approach enables the unique identification of nonadditive information costs. The nonadditivity of information costs makes the effective cost inherently dependent on benefits of information. In contrast to additive cost models, this feature may lead to a violation of the preference for early resolution of menu uncertainty. Early resolution is typically preferable as it allows the agent to fine-tune information for relevant menus. However, if the effective cost function is convex in benefits of information, late resolution may reduce the effective information costs. The violation occurs when this cost-reduction effect outweighs the benefits of early resolution. en-copyright= kn-copyright= en-aut-name=HigashiYouichiro en-aut-sei=Higashi en-aut-mei=Youichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HyogoKazuya en-aut-sei=Hyogo en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakeokaNorio en-aut-sei=Takeoka en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Faculty of Economics, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Economics, Ryukoku University kn-affil= affil-num=3 en-affil=Department of Economics, Hitotsubashi University kn-affil= en-keyword=Information acquisition kn-keyword=Information acquisition en-keyword=Rational inattention kn-keyword=Rational inattention en-keyword=Preference for the timing of the resolution of uncertainty kn-keyword=Preference for the timing of the resolution of uncertainty en-keyword=Preference over menus kn-keyword=Preference over menus 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=53 cd-vols= no-issue=11 article-no= start-page=945 end-page=950 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-term and multi-stage ice accumulation in the martian mid-latitudes during the Amazonian en-subtitle= kn-subtitle= en-abstract= kn-abstract=Subsurface ice in the mid-latitudes of Mars represents one of the largest present-day water ice reservoirs. While atmospheric models predict Late Amazonian (during the past hundreds of millions of years) obliquity-driven ice accumulation, its long-term variations, and the factors influencing accumulation remain unclear. Using geomorphological evidence and numerical modeling, we reveal a southwestern depositional trend within northern mid-latitudinal crater walls and floors. Detailed crater-fill deposit analyses indicate multiple glaciation stages, including an earlier, high-intensity stage followed by a later, lower-intensity stage, both exhibiting this southwestern trend (ca. 640?98 Ma). We conclude that persistent multiple-stage Amazonian glaciations were governed by atmospheric water availability and obliquity-driven climate cycles. en-copyright= kn-copyright= en-aut-name=RujTrishit en-aut-sei=Ruj en-aut-mei=Trishit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkudaHanaya en-aut-sei=Okuda en-aut-mei=Hanaya 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=HasegawaHitoshi en-aut-sei=Hasegawa en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HeadJames W. en-aut-sei=Head en-aut-mei=James W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UsuiTomohiro en-aut-sei=Usui en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MihiraShun en-aut-sei=Mihira en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KobayashiMakito en-aut-sei=Kobayashi en-aut-mei=Makito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Kochi Institute for Core Sample Research (X-star), JAMSTEC kn-affil= affil-num=3 en-affil=International Research School of Planetary Sciences, Universit? d’Annunzio kn-affil= affil-num=4 en-affil=Department of Global Environment and Disaster Prevention, Faculty of Science and Technology, Kochi University kn-affil= affil-num=5 en-affil=Department of Earth, Environmental and Planetary Sciences, Brown 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=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=8 en-affil=Department of Systems Innovation, School of Engineering, University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=1 article-no= start-page=183 end-page=204 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=On the stratification of combinatorial spectra en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this note, we investigate a mixture of combinatorial spectra and stratified simplicial sets, which would be thought of as a model of the spectrum objects of (∞,∞)-categories. en-copyright= kn-copyright= en-aut-name=HoriuchiRyo en-aut-sei=Horiuchi en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=1 article-no= start-page=13 end-page=62 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=Natural homotopy of multipointed d-spaces en-subtitle= kn-subtitle= en-abstract= kn-abstract=We identify Grandis’ directed spaces as a full reflective subcategory of the category of multipointed d-spaces. When the multipointed d-space realizes a precubical set, its reflection coincides with the standard realization of the precubical set as a directed space. The reflection enables us to extend the construction of the natural system of topological spaces in Baues-Wirsching’s sense from directed spaces to multipointed d-spaces. In the case of a cellular multipointed d-space, there is a discrete version of this natural system which is proved to be bisimilar up to homotopy. We also prove that these constructions are invariant up to homotopy under globular subdivision. These results are the globular analogue of Dubut’s results. Finally, we point the apparent incompatibility between the notion of bisimilar natural systems and the q-model structure of multipointed d-spaces and we give some suggestions for future works. en-copyright= kn-copyright= en-aut-name=GaucherPhilippe en-aut-sei=Gaucher en-aut-mei=Philippe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Universit? Paris Cit?, CNRS, IRIF kn-affil= en-keyword=multipointed d-space kn-keyword=multipointed d-space en-keyword=globular subdivision kn-keyword=globular subdivision en-keyword=directed path kn-keyword=directed path en-keyword=natural system kn-keyword=natural system en-keyword=bisimulation kn-keyword=bisimulation en-keyword=open map kn-keyword=open map END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=11 article-no= start-page=8183 end-page=8197 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Solution Structure and Counterion Condensation of Carboxymethyl Cellulose in Organic Solvents en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report scattering (SANS and SAXS) and electrical conductivity data for aqueous and organic solutions of carboxymethyl cellulose with tetrabutylammonium counterions. For SANS in deuterated solvents, the contrast is heavily dominated by the hydrogen-rich counterions, while for SAXS the polymer backbone has a more significant contribution to the scattering signal. The correlation length calculated from the SAXS measurements follows a scaling law of ξ ∝ c?1/2, while that measured by SANS displays a weaker exponent at higher concentrations for solvents of high dielectric constants. These results indicate a decoupling in the characteristic length scales of fluctuations of the polymer backbone and counterions at high polyelectrolyte concentrations. The stretching parameter calculated from the correlation length indicates a highly stretched local conformation for TBACMC in water and several high dielectric constant solvents, consistent with the semiflexible nature of the cellulose backbone. In solvents of lower dielectric permittivity, the chains display a higher degree of local coiling. Combining electrical conductivity and scattering data, we find that the fraction of monomers bearing a dissociated charge is nearly independent of concentration and approximately proportional to the reciprocal of the Bjerrum length of the solvent, as expected by the Oosawa-Manning model. en-copyright= kn-copyright= en-aut-name=GulatiAnish en-aut-sei=Gulati en-aut-mei=Anish kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MengLingzi en-aut-sei=Meng en-aut-mei=Lingzi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=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= affil-num=1 en-affil=Institute of Physical Chemistry, RWTH Aachen University kn-affil= affil-num=2 en-affil=Materials Science and Engineering Department, The Pennsylvania State University kn-affil= affil-num=3 en-affil=Institute of Physical Chemistry, RWTH Aachen University kn-affil= affil-num=4 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Materials Science and Engineering Department, The Pennsylvania State University kn-affil= en-keyword=polyelectrolyte kn-keyword=polyelectrolyte en-keyword=scattering kn-keyword=scattering en-keyword=conductivity kn-keyword=conductivity en-keyword=cellulose kn-keyword=cellulose en-keyword=condensation kn-keyword=condensation END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue= article-no= start-page=rbae144 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Optimizing β-TCP with E-rhBMP-2-infused fibrin for vertical bone regeneration in a mouse calvarium model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Effective reconstruction of large bone defects, particularly in thickness, remains one of the major challenges in orthopedic and dental fields. We previously produced an Escherichia coli-based industrial-scale GMP-grade recombinant human bone morphogenetic protein-2 (E-rhBMP-2) and showed that the combination of E-rhBMP-2 with beta-tricalcium phosphate (β-TCP/E-rhBMP-2) can effectively promote bone reconstruction. However, the limited mechanical strength and poor morphology retention of β-TCP granules are key points that need optimization to obtain more effective grafts and further expand its clinical applications. Therefore, we combined β-TCP/E-rhBMP-2 with fibrin gel to enhance its mechanical properties and usability for vertical bone regeneration. We investigated the mechanical properties and vertical bone regeneration effects of the materials applied, with or without fibrin containing E-rhBMP-2, in a calvarial defect model in mice. Compression tests were conducted to assess the initial stability of the materials. Scanning electron microscopy and Fourier transform infrared spectroscopy were conducted to characterize the presence of fibrin on the scaffold. After 4 and 12?weeks of implantation, micro-computed tomography and histological and immunofluorescent analyses were performed to assess the morphology and volume of the newly formed bone. The fibrin-containing groups had significantly higher initial mechanical strength and higher ability to maintain their morphology in vivo compared to the counterparts without fibrin. However, fibrin gel alone suppressed the bone formation ability of β-TCP/E-rhBMP-2 whereas the presence of high doses of E-rhBMP-2 in fibrin gel resulted in material resorption and enhanced new bone formation. In conclusion, fibrin gel significantly improved the mechanical strength and surgical manageability of the β-TCP/E-rhBMP-2 scaffold, and the addition of E-rhBMP-2 to the fibrin gel further enhanced the vertical bone regeneration and initial structural integrity of the scaffold. en-copyright= kn-copyright= en-aut-name=ZhaoKun en-aut-sei=Zhao en-aut-mei=Kun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MuXindi en-aut-sei=Mu en-aut-mei=Xindi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=XieShichao en-aut-sei=Xie en-aut-mei=Shichao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YonezawaTomoko en-aut-sei=Yonezawa en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkadaMasahiro en-aut-sei=Okada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumotoTakuya en-aut-sei=Matsumoto en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KubokiTakuo en-aut-sei=Kuboki en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OohashiToshitaka en-aut-sei=Oohashi en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Division of Dental Biomaterials, Tohoku University Graduate School of Dentistry kn-affil= affil-num=8 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=BMP-2 kn-keyword=BMP-2 en-keyword=fibrin kn-keyword=fibrin en-keyword=vertical bone regeneration kn-keyword=vertical bone regeneration en-keyword=biocompatible materials kn-keyword=biocompatible materials END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=1 article-no= start-page=12 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250320 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Early Response After Radiation Therapy on Three-Dimensional Oral Cancer Model Using Patient-Derived Cancer-Associated Fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Cancer-associated fibroblasts (CAFs), which are an important component of the tumor microenvironment, have been reported to have an adverse effect on conventional radiotherapy. This study aims to elucidate the effects of CAFs in boron neutron capture therapy (BNCT) using a three-dimensional (3D) oral cancer model. Methods: Three-dimensional cancer models were fabricated using patient-derived CAFs or patient-derived normal oral fibroblasts (NOFs) and a human oral squamous cell carcinoma cell line. Each 3D cancer model was performed with either a conventional X-ray treatment or BNCT and additionally analyzed histomorphologically. Results: The 3D oral cancer-CAFs model demonstrated a greater depth of cancer cell invasion than the 3D oral cancer-NOFs model. Radiation therapy for the 3D oral cancer models indicated a trend for decreasing cancer cell invasion and cell number with dose dependence in both X-ray and BNCT. In comparison with X-rays, BNCT showed a consistent increase in the number of NOFs and a significant reduction in the number of CAFs. Conclusions: BNCT for the 3D oral cancer model was shown to be effective against cancer cells and CAFs but not against NOFs, indicating its usefulness as a minimally invasive treatment for advanced cancer. Furthermore, it is indicated that the 3D oral cancer-CAFs model is a valuable tool to evaluate cancer treatment and research, particularly in high-grade malignant tumors with invasion. en-copyright= kn-copyright= en-aut-name=YamamotoIzumi en-aut-sei=Yamamoto en-aut-mei=Izumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IgawaKazuyo en-aut-sei=Igawa en-aut-mei=Kazuyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoNatsuko en-aut-sei=Kondo en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakuraiYoshinori en-aut-sei=Sakurai en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HuangPeng en-aut-sei=Huang en-aut-mei=Peng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=IzumiKenji en-aut-sei=Izumi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=2 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=3 en-affil=Particle Radiation Oncology Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=4 en-affil=Particle Radiation Oncology Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=5 en-affil=Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=8 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= en-keyword=3D model kn-keyword=3D model en-keyword=oral cancer kn-keyword=oral cancer en-keyword=patient-derived cells kn-keyword=patient-derived cells en-keyword=cancer-associated fibroblasts kn-keyword=cancer-associated fibroblasts en-keyword=radiation treatment kn-keyword=radiation treatment en-keyword=boron neutron capture therapy kn-keyword=boron neutron capture therapy en-keyword=malignant tumors kn-keyword=malignant tumors END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=6 article-no= start-page=324 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250531 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Global Incidence Trend of Early-Onset Obesity-Related and Non-Obesity-Related Cancers en-subtitle= kn-subtitle= en-abstract= kn-abstract=The global rise in obesity prevalence and the incidence of early-onset cancer (diagnosed between 20 and 49 years of age) is a serious public health concern. We, therefore, evaluated the recent global trends in the incidence of early-onset obesity-related cancers and compared them to those of non-obesity-related cancers. We obtained age-standardized incidence rates of early-onset cancers diagnosed between 2000 and 2012 in 44 countries from the Cancer Incidence in Five Continents database. Using joinpoint regression models, we calculated the average annual percentage changes (AAPCs) and their corresponding 95% confidence intervals (95% CIs) for combined and individual categories of obesity-related cancers (11 and 9 cancer types in females and males, respectively) and non-obesity-related cancers (12 cancer types in both females and males). Differences in the AAPC were assessed by comparing 95% CIs, where nonoverlapping 95% CIs were considered statistically significantly different. We observed statistically significant positive AAPCs for early-onset obesity-related cancers in all available countries combined among females (global AAPC, 4.3%; 95% CI, 4.1?4.6%) and males (global AAPC, 1.4%; 95% CI, 1.2?1.7%). When analyzed by countries, we observed statistically significant positive AAPCs in 26 countries among females and 11 countries among males. AAPCs for early-onset obesity-related cancers were statistically significantly higher than those of non-obesity-related cancers in several regions, especially North America and Oceania. In conclusion, this study indicates that the incidence of early-onset obesity-related cancers exhibited a more pronounced increasing trend than non-obesity-related cancers among both sexes in many countries and regions. en-copyright= kn-copyright= en-aut-name=TerashimaMiyu en-aut-sei=Terashima en-aut-mei=Miyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakayamaKota en-aut-sei=Nakayama en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UgaiSatoko en-aut-sei=Ugai en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LeeHwa-Young en-aut-sei=Lee en-aut-mei=Hwa-Young kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsukumoYuta en-aut-sei=Tsukumo en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MizunoHiroki en-aut-sei=Mizuno en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SongMinkyo en-aut-sei=Song en-aut-mei=Minkyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SasamotoNaoko en-aut-sei=Sasamoto en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawachiIchiro en-aut-sei=Kawachi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UgaiTomotaka en-aut-sei=Ugai en-aut-mei=Tomotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Okayama University Medical School kn-affil= affil-num=2 en-affil=Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA kn-affil= affil-num=4 en-affil=Graduate School of Public Health and Healthcare Management, The Catholic University of Korea kn-affil= affil-num=5 en-affil=Department of Epidemiology, Harvard T.H. Chan School of Public Health kn-affil= affil-num=6 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Epidemiology, Harvard T.H. Chan School of Public Health kn-affil= affil-num=8 en-affil=Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health kn-affil= affil-num=9 en-affil=Public Health Sciences Division, Fred Hutchinson Cancer Center kn-affil= affil-num=10 en-affil=Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health kn-affil= affil-num=11 en-affil=Department of Epidemiology, Harvard T.H. Chan School of Public Health kn-affil= en-keyword=neoplasms kn-keyword=neoplasms en-keyword=etiology kn-keyword=etiology en-keyword=risk factors kn-keyword=risk factors en-keyword=global health kn-keyword=global health en-keyword=young adults kn-keyword=young adults 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=295 cd-vols= no-issue= article-no= start-page=51 end-page=64 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=A novel spontaneous rat model of chronic kidney disease with mitochondrial dysfunction driven by thioredoxin insufficiency en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Chronic kidney disease (CKD) is a global health burden with high prevalence and poor prognosis. Although oxidative stress and mitochondrial dysfunction have been implicated in its pathogenesis, in vivo causal evidence remains limited. Thioredoxin (Trx), encoded by Txn1, is a redox-active protein that plays a central role in controlling oxidative stress and maintaining intracellular redox homeostasis.
Methods: To address this gap, we investigated the lifelong phenotypes of Txn1-F54L mutant rats harboring approximately one-third of the normal Trx activity. These rats were generated via N-ethyl-N-nitrosourea mutagenesis and validated by clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 genome editing. Comprehensive analyses included biochemical testing, histopathology, immunohistochemistry, transmission electron microscopy, RNA-sequencing, western blotting, and cytokine profiling.
Results: Txn1-F54L mutant rats spontaneously developed progressive CKD, with median survival times of 110?119 days for homozygotes and 303?346 days for heterozygotes. Their clinical features?elevated blood urea nitrogen, hypoalbuminemia, hypercholesterolemia, hypertension, and arterial medial sclerosis?closely resembled those of human CKD. Histopathological evaluation revealed extensive tubular injury, interstitial fibrosis, and glomerulosclerosis. Transcriptomic profiling identified 3,418 differentially expressed genes significantly enriched in immune activation and fibrosis pathways. Mitochondrial dysfunction was prominent in proximal tubules, accompanied by oxidative stress accumulation and concurrent activation of regulated cell death pathways (apoptosis, necroptosis, and pyroptosis). Elevated serum levels of interleukin-1β, interleukin-6, and interferon-γ indicated systemic inflammation.
Conclusions: Our findings demonstrate that lifelong Trx deficiency induces oxidative stress?mediated mitochondrial dysfunction and regulated cell death, leading to inflammation and progressive CKD. This study establishes the Txn1 mutant rat as a valuable spontaneous CKD model, providing translational insights and a platform for developing therapeutic strategies targeting oxidative stress?induced pathways. en-copyright= kn-copyright= en-aut-name=OhmoriIori K. en-aut-sei=Ohmori en-aut-mei=Iori K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HadaYoshiko en-aut-sei=Hada en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=ToyokuniShinya en-aut-sei=Toyokuni en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MashimoTomoji en-aut-sei=Mashimo en-aut-mei=Tomoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Section of Developmental Physiology and Pathology, Faculty of Education, Okayama University kn-affil= affil-num=2 en-affil=Department of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Division of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo kn-affil= en-keyword=Chronic kidney disease kn-keyword=Chronic kidney disease en-keyword=Mitochondria kn-keyword=Mitochondria en-keyword=Thioredoxin kn-keyword=Thioredoxin en-keyword=Trx kn-keyword=Trx en-keyword=Txn1 kn-keyword=Txn1 en-keyword=Regulated cell death kn-keyword=Regulated cell death 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 ?-Batch Sequential Deployment mechanism for privacy-preserving multi-domain SFC deployment. Instead of evaluating whole-chain feasibility at once, the proposed ?-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 ?-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 ?-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=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=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=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=330 cd-vols= no-issue=5 article-no= start-page=L593 end-page=L609 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=The role of S100A8/A9 in the pathogenesis of acute exacerbations of pulmonary fibrosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Acute exacerbation of idiopathic pulmonary fibrosis is a life-threatening condition characterized by neutrophilic inflammation. S100A8/A9, an alarmin released by activated neutrophils and monocytes/macrophages, plays a pivotal role in regulating inflammatory responses. However, its specific involvement in acute exacerbations of pulmonary fibrosis remains unclear. This study evaluated the role of S100A8/A9 in the pathogenesis of acute exacerbations of pulmonary fibrosis. S100A8/A9 levels were measured in bronchoalveolar lavage fluid and serum from patients with idiopathic interstitial pneumonia, with and without acute exacerbations. To model acute exacerbations of pulmonary fibrosis, mice were intratracheally administered bleomycin followed by lipopolysaccharide. Subsequently, inflammatory cell infiltration, cytokine levels, morphological changes, and fibrosis marker levels in lung tissue and airways were analyzed. S100A8/A9 levels were significantly higher in the bronchoalveolar lavage fluid and serum of patients with idiopathic interstitial pneumonia experiencing acute exacerbations relative to those without; these levels were correlated with patient prognosis. In an experimental mouse model, intratracheal administration of bleomycin followed by lipopolysaccharide resulted in a significant increase in airway S100A8/A9 levels compared with bleomycin alone and control mice. Anti-S100A8/A9 neutralizing antibody Ab45 mitigated airway inflammation and lung fibrosis in mice with acute exacerbations of pulmonary fibrosis, reducing S100A8/A9 levels and neutrophil extracellular traps. In vitro, recombinant S100A8/A9 or lipopolysaccharide and neutrophils activated and differentiated fibroblasts; these effects were inhibited by anti-S100A8/A9 neutralizing antibody Ab45 and the humanized form of Ab45 (HuAb45). These findings highlight S100A8/A9 as a potential prognostic biomarker and therapeutic target for acute exacerbations of pulmonary fibrosis. en-copyright= kn-copyright= en-aut-name=NakamuraNaoki en-aut-sei=Nakamura en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=TaniguchiAkihiko en-aut-sei=Taniguchi en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OzekiTaichi en-aut-sei=Ozeki en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SunamiRyota en-aut-sei=Sunami en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=InukaiYumi en-aut-sei=Inukai en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=ItanoJunko en-aut-sei=Itano en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaAyaka en-aut-sei=Tanaka en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MiyaharaNobuaki en-aut-sei=Miyahara en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Medical Laboratory Science, Okayama University Faculty of Health Sciences kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Kurashiki Central Hospital kn-affil= affil-num=11 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=anti-S100A8/A9 neutralizing antibody kn-keyword=anti-S100A8/A9 neutralizing antibody en-keyword=calprotectin kn-keyword=calprotectin en-keyword=idiopathic pulmonary fibrosis kn-keyword=idiopathic pulmonary fibrosis en-keyword=lipopolysaccharide kn-keyword=lipopolysaccharide en-keyword=neutrophil extracellular traps kn-keyword=neutrophil extracellular traps 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=20260521 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Stimulator of interferon genes agonist augmented antitumor immunity of osimertinib in Egfr ‐mutated lung?cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers (NSCLCs) lack effective immunotherapy due to a noninflamed tumor microenvironment (TME). We previously reported that EGFR tyrosine-kinase-inhibitor (TKI) induced CD8+ T-cell immunity, which was insufficient for tumor eradication. We evaluated the potential of combining EGFR-TKI with stimulator of interferon genes (STING) agonists in activating a systemic antitumor response. Using a syngeneic mouse model of genetically engineered Egfr-mutant NSCLC, we evaluated the antitumor effects of STING agonist ADU-S100, alone and combined with osimertinib. Immunohistochemistry and flow cytometry were used to assess the TME. Osimertinib alone enhanced CD8+ T-cell infiltration but not Natural Killer (NK) cell infiltration. ADU-S100 injection alone modestly suppressed tumor growth with increasing CD8+/NK cell infiltration in the TME, but lacked an abscopal effect. Combining ADU-S100 with osimertinib significantly enhanced the antitumor effects and CD8+/NK cell infiltration. Depletion of either CD8+ or NK cells reduced the combination effect. Crucially, the combination induced an abscopal effect accompanied by PD-1+/CD8+ cell infiltration. Combining osimertinib with a STING agonist augmented innate and adaptive immunity, inducing systemic antitumor responses in EGFR-mutant NSCLC. en-copyright= kn-copyright= en-aut-name=NishimuraJun en-aut-sei=Nishimura en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Br?gelmannJohannes en-aut-sei=Br?gelmann en-aut-mei=Johannes kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkawaSachi en-aut-sei=Okawa en-aut-mei=Sachi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaokaMasataka en-aut-sei=Taoka en-aut-mei=Masataka 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=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=TanakaTakaaki en-aut-sei=Tanaka en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=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=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KatayamaRyohei en-aut-sei=Katayama en-aut-mei=Ryohei 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=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SosMartin L. en-aut-sei=Sos en-aut-mei=Martin L. 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= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 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 Translational Genomics Faculty of Medicine and University Hospital Cologne, University of Cologne Germany 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=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Division of Experimental Chemotherapy, Cancer Chemotherapy Centre, Japanese Foundation for Cancer Research kn-affil= affil-num=14 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Translational Genomics Faculty of Medicine and University Hospital Cologne, University of Cologne Germany kn-affil= affil-num=19 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=20 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=abscopal effect kn-keyword=abscopal effect en-keyword=CD8+ T cells kn-keyword=CD8+ T cells en-keyword=EGFR mutation kn-keyword=EGFR mutation en-keyword=EGFR tyrosine kinase inhibitor kn-keyword=EGFR tyrosine kinase inhibitor en-keyword=NK cells kn-keyword=NK cells en-keyword=stimulator of interferon genes kn-keyword=stimulator of interferon genes 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=17 cd-vols= no-issue=1 article-no= start-page=4963 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural insights into YheS-mediated release of SecM-arrested ribosome en-subtitle= kn-subtitle= en-abstract= kn-abstract=ATP-binding cassette subfamily F (ABCF) proteins interact with the ribosome to resolve translation defects near the peptidyl transferase center (PTC). In Escherichia coli, four ABCF proteins (EttA, Uup, YbiT, and YheS) selectively promote translation of distinct problematic nascent peptide sequences, but their molecular mechanisms remain unclear. Here, we present a 2.8?? cryo-EM structure of the ribosome in complex with an ATPase-deficient mutant of YheS and investigate how it releases ribosomes arrested by the SecM nascent chain. YheS binds to the ribosomal E-site via the L1 stalk, and its P-site tRNA-interaction motif (PtIM) extends toward the PTC, displacing the CCA end of the P-site tRNA. Notably, the cryo-EM density corresponding to the SecM nascent chain within the exit tunnel is largely lost upon YheS binding. These observations suggest that YheS relieves peptide sequence-dependent stalling by perturbing nascent chain-tunnel interactions through P-site tRNA relocation. Steered molecular dynamics simulations provide qualitative support for this model. Together, our findings provide mechanistic insight into a mode of arrest release distinct from the translocon-mediated release mechanism. en-copyright= kn-copyright= en-aut-name=IsoKaishi en-aut-sei=Iso en-aut-mei=Kaishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaToma en-aut-sei=Ikeda en-aut-mei=Toma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamasakiKohei en-aut-sei=Yamasaki en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AndoYushin en-aut-sei=Ando en-aut-mei=Yushin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SanoFumiya K. en-aut-sei=Sano en-aut-mei=Fumiya K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FurutaTadaomi en-aut-sei=Furuta en-aut-mei=Tadaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TaguchiHideki en-aut-sei=Taguchi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NurekiOsamu en-aut-sei=Nureki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ChadaniYuhei en-aut-sei=Chadani en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItohYuzuru en-aut-sei=Itoh en-aut-mei=Yuzuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=2 en-affil=School of Life Science and Technology, Institute of Science Tokyo 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=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=6 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=7 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=8 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=9 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= 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= article-no= start-page=1756863 end-page=1756863 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=Behavior of serum thyroglobulin in relation to thyroid function under low-thyrotropin conditions in general practice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Serum thyroglobulin (Tg) and thyroid hormones are essential biomarkers in the diagnosis and management of thyroid diseases. Although Tg is routinely measured as a marker for thyroid neoplasia and an adjunct in the diagnosis of thyrotoxicosis due to destructive thyroiditis, its clinical significance under conditions of abnormal thyroid function remains unclear.
Methods: We investigated the association between serum Tg levels and thyroid function in 292 patients who underwent simultaneous evaluation of serum Tg, free thyroxine (FT4), and free triiodothyronine (FT3) levels in routine clinical practice. Based on thyroid-stimulating hormone (TSH) levels, participants were classified into three groups: high-TSH (> 4.23 μIU/mL; n = 38), normal-TSH (0.61?4.23 μIU/mL; n = 191), and low-TSH (< 0.61 μIU/mL; n = 63).
Results: The low-TSH group exhibited significantly higher serum Tg levels (118.66 ± 32.13 ng/mL) than the normal-TSH (70.20 ± 23.48 ng/mL) and high-TSH (34.70 ± 13.62 ng/mL) groups. Among patients positive for TSH-receptor antibodies (TRAb) or thyroid-stimulating antibodies (TSAb), elevated Tg levels were observed exclusively in the low-TSH group. Correlation analyses revealed that Tg levels were positively correlated with the FT3/FT4 ratio in the low-TSH group (rho = 0.62, p < 0.01), and this association was more evident in patients positive for both TRAb and TSAb (rho = 0.71, p < 0.01). These associations remained significant after multivariable adjustment and were supported by correlations between Tg and SPINA-GD, a model-based index of thyroid function reflecting deiodinase activity, with similar findings observed in patients with autoimmune hyperthyroidism.
Conclusion: These findings suggest that serum Tg levels may reflect biochemical features consistent with T3 predominance in autoimmune hyperthyroidism and have potential clinical utility in characterizing disease pathophysiology. en-copyright= kn-copyright= en-aut-name=SazumiYosuke en-aut-sei=Sazumi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=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=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=YamamotoKoichiro en-aut-sei=Yamamoto en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuyamaAtsuhito en-aut-sei=Suyama en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakaseRyosuke en-aut-sei=Takase en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=YasudaMiho en-aut-sei=Yasuda en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FurukawaMasanori en-aut-sei=Furukawa en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=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=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Laboratory Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=FT3/FT4 ratio kn-keyword=FT3/FT4 ratio en-keyword=hyperthyroidism kn-keyword=hyperthyroidism en-keyword=iodothyronine deiodinase kn-keyword=iodothyronine deiodinase en-keyword=thyroglobulin kn-keyword=thyroglobulin en-keyword=TSH- receptor antibody kn-keyword=TSH- receptor antibody END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=7 article-no= start-page=1181 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260407 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Predictive Nomogram for Recurrence After Upfront Surgery for Resectable Pancreatic Ductal Adenocarcinoma: A Multicenter Study (OS-HBP-2) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Postoperative recurrence is a critical issue in the treatment of resectable pancreatic ductal adenocarcinoma (rPDAC). Moreover, the prognosis after early recurrence is extremely poor. This study aimed to develop a recurrence prediction model and to define early recurrence after upfront surgery (UFS) for rPDAC. Methods: This multicenter retrospective study included patients who underwent UFS for anatomically rPDAC between January 2013 and December 2017. Multivariate analyses were conducted to identify the risk factors for recurrence-free survival and to construct a recurrence prediction model. Subsequently, a minimum p value approach was used to determine the optimal cutoff values for early and late recurrence. Results: The cohort included 603 patients (325 men and 278 women). During the median follow-up period of 25 months (interquartile range, 15?38 months), 381 patients (63.2%) experienced a recurrence. Multivariate analyses revealed carbohydrate antigen 19-9 ?37 U/mL (hazard ratio [HR], 1.58; p < 0.001), tumor size ? 2.2 cm (HR, 1.59; p < 0.001), lymph node metastasis (HR, 1.86; p < 0.001), R1 resection (HR, 1.56; p = 0.002), and no adjuvant chemotherapy (HR, 1.54; p < 0.001) as independent predictors. The recurrence prediction model demonstrated an area under the curve of 0.72?0.75. The optimal threshold for early and late recurrences was a recurrence-free interval of five months. Carbohydrate antigen 19-9 ? 156 U/mL was a significant predictor of early recurrence (OR, 3.28; p < 0.001). Conclusions: This study identified the prognostic risk factors for recurrence and developed a recurrence prediction model for patients undergoing UFS for rPDAC. Moreover, a recurrence-free interval of five months was identified as the optimal threshold for distinguishing between early and late recurrences. en-copyright= kn-copyright= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=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, 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 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, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 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=recurrence kn-keyword=recurrence en-keyword=nomogram kn-keyword=nomogram 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=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=33 cd-vols= no-issue=5 article-no= start-page=e70494 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=Comparative Efficacy of First-Line Immune Checkpoint Inhibitor-Based Combination Therapies in Patients With Sarcomatoid Renal Cell Carcinoma: A Japanese Multicenter Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Sarcomatoid renal cell carcinoma (sRCC) is an aggressive histological variant associated with a poor prognosis. While immune checkpoint inhibitor (ICI)-based combinations have become the standard of care, the optimal first-line regimen, specifically dual immunotherapy (IO-IO) vs. IO plus tyrosine kinase inhibitor (IO-TKI), remains controversial. We herein examined the real-world clinical outcomes of Japanese patients with sRCC.
Methods: We conducted a retrospective multicenter study on 46 patients with advanced or metastatic sRCC receiving first-line ICI-based combination therapy between January 2018 and December 2024 (IO-IO: n =?18; IO-TKI: n =?28). In a comparative survival analysis, three favorable-risk patients in the IO-TKI group were excluded to align risk profiles, focusing on intermediate/poor-risk groups (n =?43). The primary endpoint was overall survival (OS).
Results: In the entire cohort (n =?46), the objective response rate was numerically higher in the IO-TKI group (64.3%) than in the IO-IO group (50.0%) (p =?0.37). In the comparative analysis of intermediate/poor-risk patients (n =?43), progression-free survival (PFS) was slightly longer (p =?0.071), and OS was significantly longer (p =?0.016) in the IO-TKI group than in the IO-IO group. A multivariable analysis adjusted for IMDC risk categories showed favorable survival with the IO-TKI regimen (HR 0.37, p =?0.061).
Conclusions: The present study indicates that first-line IO-TKI combination therapy represents a promising treatment option with a potential survival advantage over IO-IO therapy for Japanese patients with sRCC. However, due to the retrospective design and small sample size, reliably determining the comparative efficacy of these regimens remains challenging, and further validation is warranted. en-copyright= kn-copyright= en-aut-name=TamuraKeita en-aut-sei=Tamura en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsushitaYuto en-aut-sei=Matsushita en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeHiromitsu en-aut-sei=Watanabe en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=MorinakaHirofumi en-aut-sei=Morinaka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=ToyodaShingo en-aut-sei=Toyoda en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NukayaTakuhisa en-aut-sei=Nukaya en-aut-mei=Takuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MaenosonoRyoichi en-aut-sei=Maenosono en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KomuraKazumasa en-aut-sei=Komura en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujitaKazutoshi en-aut-sei=Fujita en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakaharaKiyoshi en-aut-sei=Takahara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AzumaHaruhito en-aut-sei=Azuma en-aut-mei=Haruhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=InamotoTeruo en-aut-sei=Inamoto en-aut-mei=Teruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Urology, Hamamatsu University School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, Hamamatsu University School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Hamamatsu University School of Medicine kn-affil= affil-num=4 en-affil=Department of Urology, Jikei University School of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, Jikei University School of Medicine kn-affil= affil-num=6 en-affil=Department of Urology, Kawasaki Medical School 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, Kindai University Faculty of Medicine kn-affil= affil-num=9 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= affil-num=10 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=11 en-affil=Department of Urology, Kawasaki Medical School 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, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= affil-num=15 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=16 en-affil=Department of Urology, Hamamatsu University School of Medicine kn-affil= en-keyword=dual immunotherapy kn-keyword=dual immunotherapy en-keyword=immune checkpoint inhibitor kn-keyword=immune checkpoint inhibitor en-keyword=immunotherapy plus tyrosine kinase inhibitor kn-keyword=immunotherapy plus tyrosine kinase inhibitor en-keyword=sarcomatoid renal cell carcinoma kn-keyword=sarcomatoid renal cell carcinoma END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue= article-no= start-page=73466 end-page=73478 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=Construction of a Lightweight Simulation Environment Based on Topological Mapping en-subtitle= kn-subtitle= en-abstract= kn-abstract=Autonomous mobile robots require safe and efficient environmental representations for traversability-aware navigation and learning. In particular, self-learning of traversability from real-world driving experience can require robots to operate near the limits of their mobility, which introduces physical risks such as falls, malfunctions, or hardware damage. To provide a safer complementary environment for such validation and future learning, this paper proposes ATC-Mesh. This framework constructs a lightweight, simulation-ready mesh environment from the topological map produced by Adaptive Resonance Theory-based Topological Clustering with Different Topologies (ATC-DT) using high-density LiDAR point clouds. Unlike standard mesh reconstruction methods that directly process dense point clouds, ATC-Mesh generates a compact mesh from the node?edge structure of the topological map while preserving traversability attributes associated with the topological map. Experiments using two real-world LiDAR datasets show that ATC-Mesh achieves competitive mesh-construction quality compared with standard baseline methods while reducing construction time and mesh size. Gazebo experiments further show that the generated meshes can support waypoint-based navigation with a low simulation load. en-copyright= kn-copyright= en-aut-name=KatoYukinaga en-aut-sei=Kato en-aut-mei=Yukinaga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=MatsunoTakayuki en-aut-sei=Matsuno en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= en-keyword=Autonomous mobile robot kn-keyword=Autonomous mobile robot en-keyword=topological map kn-keyword=topological map en-keyword=digital twin kn-keyword=digital twin END start-ver=1.4 cd-journal=joma no-vol=194 cd-vols= no-issue= article-no= start-page=118923 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=Elucidation of mechanisms underlying the therapeutic effects of cordycepin on pulmonary hypertension, with a focus on cell senescence and gut microbiota en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Pulmonary hypertension (PH) is a progressive cardiopulmonary disorder characterized by excessive pulmonary vascular remodeling and aberrant proliferation of pulmonary artery smooth muscle cells (PASMCs). Emerging evidence suggests that gut microbiota dysbiosis contributes to PH development. Cordycepin, a natural adenosine analogue derived from Cordyceps militaris, has demonstrated antiproliferative and microbiota-modulating properties; however, its mechanism of action in PH remains unclear.
Objective: Elucidate the mechanisms underlying the therapeutic effects of cordycepin on PH, focusing on cellular senescence and gut microbiota.
Methods: The effects of cordycepin on PH pathology were investigated by transcriptome analysis of PASMCs from patients, and metagenomic analysis of rodent PH models. Cellular senescence was analyzed in lung tissue from p16Ink4a-CreERT2 reporter mice and in rat bone marrow-derived macrophages (BMDMs).
Results: RNA sequencing analysis revealed activation of p53 signaling by cordycepin in PASMCs. Cordycepin suppressed CDK1 expression and TERT phosphorylation at threonine 249. It ameliorated vascular and cardiac remodeling in PH rat and mouse models. Cordycepin induced M1-like macrophage senescence in p16 Ink4a reporter mice lungs and rat BMDMs. Cordycepin significantly reshaped the gut microbiota, increasing beneficial genera (e.g. Alistipes and Acetatifactor) and reducing proinflammatory taxa (e.g., Ruminococcus), with modulating key metabolic pathways, including short-chain fatty acid, tryptophan, and vitamin K2 metabolism.
Conclusion: Cordycepin exerts multi-target therapeutic effects in PH by inhibiting PASMC proliferation via the p53?CDK1/pTERT axis, modulating gut microbiota-linked immunometabolism and induces proinflammatory macrophage senescence. These findings support cordycepin as a promising candidate for PH therapies targeting the vascular, immune, and gut?lung axes. en-copyright= kn-copyright= en-aut-name=LiGaopeng en-aut-sei=Li en-aut-mei=Gaopeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZhaoZhixin en-aut-sei=Zhao en-aut-mei=Zhixin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MachitaniMitsuhiro en-aut-sei=Machitani en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshikawaRyou en-aut-sei=Ishikawa en-aut-mei=Ryou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshikawaKaori en-aut-sei=Ishikawa en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YokotaNaoya en-aut-sei=Yokota en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HabaReiji en-aut-sei=Haba en-aut-mei=Reiji 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=SunZhihong en-aut-sei=Sun en-aut-mei=Zhihong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KuraharaLin-Hai en-aut-sei=Kurahara en-aut-mei=Lin-Hai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HiranoKatsuya en-aut-sei=Hirano en-aut-mei=Katsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=2 en-affil=Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University kn-affil= affil-num=3 en-affil=Division of Cancer Stem Cell, National Cancer Center Research Institute kn-affil= affil-num=4 en-affil=Department of Diagnostic Pathology, Kagawa University Hospital kn-affil= affil-num=5 en-affil=Department of General Medicine, Kagawa University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University kn-affil= affil-num=7 en-affil=Department of Diagnostic Pathology, Kagawa University Hospital kn-affil= affil-num=8 en-affil=Center for Advanced Heart Failure, Okayama University Hospital kn-affil= affil-num=9 en-affil=Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University kn-affil= affil-num=10 en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=11 en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University kn-affil= en-keyword=Pulmonary hypertension kn-keyword=Pulmonary hypertension en-keyword=p53 kn-keyword=p53 en-keyword=CDK1 kn-keyword=CDK1 en-keyword=TERT kn-keyword=TERT en-keyword=p16 kn-keyword=p16 en-keyword=Microbiota kn-keyword=Microbiota 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? 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=16 cd-vols= no-issue=1 article-no= start-page=15771 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=Adolescent envy-like social comparison stress induces HPA axis hypoactivity and anxiety in female mice: implications for somatic symptom disorder en-subtitle= kn-subtitle= en-abstract= kn-abstract=Adolescence is a critical developmental window marked by heightened neuroplasticity and maturation of the stress response system, conferring vulnerability to psychosocial stress. Chronic stress during this period increases the risk of anxiety and depressive disorders and may contribute to somatic symptom disorder (SSD), which is characterized by medically unexplained physical complaints and shows a striking female predominance. The impact of envy-like stress arising from social comparison, a pervasive psychosocial factor in modern society, remains poorly understood. Male and female C57BL/6N mice were exposed to chronic envy-like stress from postnatal day (P)21 to P52 by housing them adjacent to enriched cages, while control mice were housed without such exposure. From P52 onward, mice underwent behavioral testing of anxiety-like behavior, exploratory activity, social interaction, spatial working memory, motor coordination, nociception, and depression-like behavior. Serum corticosterone and adrenocorticotropic hormone (ACTH) concentrations were measured to assess hypothalamic?pituitary?adrenal (HPA) axis function. Envy-like stress induced sex-specific phenotypes. Male mice exhibited hyperactivity, reduced social interaction, and impaired spatial working memory. In contrast, female mice displayed robust increases in anxiety-like behavior, impaired motor coordination, and significant reductions in basal corticosterone and ACTH levels. Chronic envy-like stress during adolescence elicits distinct, sex-dependent behavioral and endocrine alterations. The phenotype observed in female mice?characterized by heightened anxiety and lower basal HPA axis hormone levels?shares some biological features with clinical observations in SSD. This model may serve as a starting point for elucidating the mechanisms linking psychosocial stress and somatic symptoms in a sex-dependent manner. 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=Adolescence kn-keyword=Adolescence en-keyword=HPA axis kn-keyword=HPA axis en-keyword=Somatic symptom disorder (SSD) kn-keyword=Somatic symptom disorder (SSD) en-keyword=Sex differences kn-keyword=Sex differences en-keyword=Psychosocial stress kn-keyword=Psychosocial stress END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=44248 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251219 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Post-weaning maternal presence exerts a protective effect against social isolation-induced behavioural alterations in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Parental “watchful presence” is considered an important factor influencing behavioural and emotional development in offspring across mammalian species, including humans. However, the effects of such parental presence remain insufficiently understood, even in human studies. In laboratory mice, offspring are typically weaned at approximately three weeks of age, leaving the impact of post-weaning maternal presence on behavioural development largely unexplored. This study aimed to investigate whether maternal presence in an adjacent cage after weaning can attenuate behavioural effects of social isolation stress in mice. Furthermore, we sought to assess whether this experimental paradigm could serve as a novel animal model for studying the effects of parental watchful presence, with potential relevance to human parent?child relationship research. Mouse pups were weaned at postnatal day 21 and housed either adjacent to their mother (maternal presence group) or without maternal presence (control group). The pups were subsequently housed either in groups with littermates or individually until eight weeks of age. After maturation, behavioural tests were conducted to assess locomotor activity, anxiety-like behaviour, social behaviour, and depression-like behaviour. In group-housed mice, maternal presence did not influence behavioural outcomes. However, in individually housed mice, maternal presence partially attenuated social isolation-induced behavioural alterations, suggesting a subtle protective effect, including hyperlocomotion, reduced anxiety-like behaviour, and abnormal social interactions. Our findings demonstrate that maternal presence during the post-weaning period can offer a protective effect against certain behavioural abnormalities induced by social isolation stress in mice.　This simple adjacent-cage paradigm provides a novel and practical model for elucidating the impact of parental watchful presence on behavioural and emotional development, offering insights relevant to the understanding of parent?child relationships in humans. 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=KitanoEriko en-aut-sei=Kitano en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=5 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=6 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=7 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=8 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=9 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 Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical 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 Psychiatry, Kawasaki Medical School kn-affil= en-keyword=Maternal presence kn-keyword=Maternal presence en-keyword=Social isolation kn-keyword=Social isolation en-keyword=Post-weaning period kn-keyword=Post-weaning period en-keyword=Resilience kn-keyword=Resilience en-keyword=Mice kn-keyword=Mice END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=2 article-no= start-page=25 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260319 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Machine learning prediction of the Madden?Julian oscillation using reservoir computing en-subtitle= kn-subtitle= en-abstract= kn-abstract=The prediction of the Madden?Julian Oscillation (MJO), a massive tropical weather event with global socio-economic impacts, has been infamously difficult with physics-based weather prediction models. We employ the reservoir computing, a brain-inspired machine-learning technique, to construct a machine learning model that forecasts the real-time multivariate MJO index (RMM), a macroscopic variable that represents the state of the MJO. The training data was refined by development of a novel real-time band-pass filter that extracts the recurrency of MJO signals only from the past raw atmospheric data, and by selection of a suitable time-delay coordinate of the RMM that enhances the recurrency of the input data. The constructed model demonstrated the skill to forecast the time sequence of the RMM for a month from pre-developmental stages of the MJO. Examination of best-performing cases suggested that RMM sequences may be predicted for over two months in some cases. These results imply that inherent predictability limit of the MJO is longer than that has been estimated from physics-based weather prediction models. en-copyright= kn-copyright= en-aut-name=SuematsuTamaki en-aut-sei=Suematsu en-aut-mei=Tamaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaiKengo en-aut-sei=Nakai en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YonedaTsuyoshi en-aut-sei=Yoneda en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakasukaDaisuke en-aut-sei=Takasuka en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=JinnoTakuya en-aut-sei=Jinno en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SaikiYoshitaka en-aut-sei=Saiki en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiuraHiroaki en-aut-sei=Miura en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=RIKEN Center for Computational Science 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 Economics, Hitotsubashi University kn-affil= affil-num=4 en-affil=Department of Geophysics, Tohoku University kn-affil= affil-num=5 en-affil=Graduate School of Science, The University of Tokyo kn-affil= affil-num=6 en-affil=Graduate School of Business Administration, Hitotsubashi University kn-affil= affil-num=7 en-affil=Graduate School of Science, The University of Tokyo kn-affil= en-keyword=Reservoir computing kn-keyword=Reservoir computing en-keyword=Machine learning kn-keyword=Machine learning en-keyword=Madden?Julian Oscillation kn-keyword=Madden?Julian Oscillation en-keyword=Sub-seasonal forecast kn-keyword=Sub-seasonal forecast END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=10 article-no= start-page=1527 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Activation of TAS2R Signaling by Diphenidol Suppresses Tumor Growth and Remodels the Tumor Immune Microenvironment in Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Oral squamous cell carcinoma (OSCC) remains a clinically challenging malignancy characterized by aggressive behavior and limited therapeutic options. Bitter taste receptors (TAS2Rs), expressed across multiple tissues and cancer types, have recently emerged as regulators of tumor biology and immune responses; however, their functional significance in OSCC remains poorly understood. Methods: Immunohistochemical analysis was performed using surgically resected human tongue OSCC specimens and a tissue microarray (TMA) cohort. In parallel, four TAS2R agonists were evaluated in SCC7 cells to assess intracellular calcium responses. RNA sequencing was conducted to analyze transcriptional changes following diphenidol treatment, and functional assays, including proliferation, migration, and apoptosis analyses, were performed in vitro. Antitumor effects were further evaluated in a syngeneic SCC7 mouse model, followed by TUNEL staining and flow cytometry to assess apoptosis and immune cell infiltration. Results: TAS2R38 expression was markedly upregulated in dysplastic and invasive OSCC lesions with predominant nuclear localization and was associated with histological grade and clinical stage, indicating an early and sustained alteration during tumor progression. Among the agonists tested, diphenidol most strongly induced IP3-dependent intracellular Ca2+ elevation. RNA sequencing revealed upregulation of Il1rl1 and Lzts2. Functionally, diphenidol significantly suppressed SCC7 cell proliferation and migration and induced apoptosis in vitro. In vivo, diphenidol reduced tumor volume and weight and increased apoptotic activity. Flow cytometry demonstrated a marked reduction in tumor-infiltrating CD4+CD25+Foxp3+ regulatory T cells, indicating modulation of the tumor immune microenvironment. Conclusions: TAS2R activation by diphenidol suppresses tumor growth through both tumor-intrinsic mechanisms and modulation of the tumor immune microenvironment in OSCC. These findings define TAS2R-mediated calcium signaling as a novel axis linking tumor progression and immunoregulation. Given that diphenidol is a clinically approved drug with an established safety profile, our results provide a strong rationale for TAS2R-targeted drug repurposing strategies in cancer therapy. en-copyright= kn-copyright= en-aut-name=NasrunNisrina Ekayani en-aut-sei=Nasrun en-aut-mei=Nisrina Ekayani kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanimuraAkihiko en-aut-sei=Tanimura en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=UeharaOsamu en-aut-sei=Uehara en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HosoyaAkihiro en-aut-sei=Hosoya en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakebeHiroaki en-aut-sei=Takebe en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AbikoYoshihiro en-aut-sei=Abiko en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=RuslinMuhammad en-aut-sei=Ruslin en-aut-mei=Muhammad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShimoTsuyoshi en-aut-sei=Shimo en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=2 en-affil=Division of Pharmacology, Department of Oral Biology, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=3 en-affil=Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=4 en-affil=Division of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Division of Craniofacial Development and Tissue Biology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=8 en-affil=Division of Histology, Department of Oral Biology, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Hasanuddin University kn-affil= affil-num=12 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido kn-affil= en-keyword=bitter taste receptor kn-keyword=bitter taste receptor en-keyword=diphenidol kn-keyword=diphenidol en-keyword=immunometabolism kn-keyword=immunometabolism en-keyword=oral squamous cellcarcinoma kn-keyword=oral squamous cellcarcinoma en-keyword=TAS2R signaling kn-keyword=TAS2R signaling en-keyword=tumor immune microenvironment kn-keyword=tumor immune microenvironment END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=46 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=Revised taxonomy reveals sustained introgression and secondary contact in ancient lake ricefishes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Biotic diversification in ancient lakes is shaped by complex geological histories and genetic exchange among populations. The Malili Lake system on Sulawesi Island represents a classic natural laboratory for studying freshwater fish evolution and harbors multiple endemic Oryzias species that diversified under repeated hydrological reorganizations. Previous genomic analyses inferred that two sympatric species in Lake Towuti (O. profundicola and O. loxolepis) experienced a single ancient introgression event from a “ghost lineage” derived from O. marmoratus inhabiting another lake. However, recent taxonomic re-evaluation has revealed the presence of an extant O. marmoratus population within Lake Towuti itself. This finding suggests that the putative ghost lineage may in fact represent a living population co-occurring in the lake, calling for a re-examination of the introgression history and speciation mode in Lake Towuti.
Results By incorporating newly generated ddRAD-seq data from the true O. marmoratus in Lake Towuti, we reanalyzed phylogenetic relationships and population genetic structure among Malili Lake Oryzias. Previously reported major phylogenetic relationships and inter-lake introgression patterns were largely reproduced. In contrast, TreeMix and f4-statistic analyses revealed that introgression signals previously attributed to a “ghost lineage” into O. profundicola and O. loxolepis instead originated from the extant O. marmoratus population coexisting within Lake Towuti. Demographic model comparisons explicitly incorporating within-lake gene flow further supported a scenario in which O. profundicola and O. loxolepis diverged in allopatry, subsequently came into secondary contact within Lake Towuti, and later experienced additional gene flow following secondary contact with O. marmoratus that entered the lake.
Conclusion Our results demonstrate that introgression from the O. marmoratus lineage into O. profundicola and O. loxolepis was not a single ancient event, but rather a more sustained process. This finding highlights the critical importance of taxonomic resolution for accurately inferring introgression and divergence history. Comparative studies across other ancient lakes on Sulawesi will be valuable for understanding how the timing and nature of gene flow from third lineages influence patterns of population divergence and the strength of reproductive isolation. en-copyright= kn-copyright= en-aut-name=YashimaYuki en-aut-sei=Yashima en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NofriantoAndy B. en-aut-sei=Nofrianto en-aut-mei=Andy B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NuryadiHandung en-aut-sei=Nuryadi en-aut-mei=Handung kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KakiokaRyo en-aut-sei=Kakioka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiHirozumi en-aut-sei=Kobayashi en-aut-mei=Hirozumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=MandagiIxchel F. en-aut-sei=Mandagi en-aut-mei=Ixchel F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MasengiKawilarang W. A. en-aut-sei=Masengi en-aut-mei=Kawilarang W. A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=LawelleSjamsu A. en-aut-sei=Lawelle en-aut-mei=Sjamsu A. 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=KusumiJunko en-aut-sei=Kusumi en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamahiraKazunori en-aut-sei=Yamahira en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=Tropical Biosphere Research Center, University of the Ryukyus kn-affil= affil-num=4 en-affil=Department of Applied Aquabiology, National Fisheries University kn-affil= affil-num=5 en-affil=The Natural History Museum and Institute kn-affil= affil-num=6 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=7 en-affil=Faculty of Fisheries and Marine Science, Sam Ratulangi University kn-affil= affil-num=8 en-affil=Faculty of Fisheries and Marine Science, Sam Ratulangi University kn-affil= affil-num=9 en-affil=Faculty of Fisheries and Marine Science, Halu Oleo University kn-affil= affil-num=10 en-affil=Bioscience and Biotechnology Center, Nagoya University kn-affil= affil-num=11 en-affil=Faculty of Social and Cultural Studies, Kyushu University kn-affil= affil-num=12 en-affil=Tropical Biosphere Research Center, University of the Ryukyus kn-affil= en-keyword=Demography kn-keyword=Demography en-keyword=Hybridization kn-keyword=Hybridization en-keyword=Malili Lakes kn-keyword=Malili Lakes en-keyword=Oryzias kn-keyword=Oryzias en-keyword=Speciation kn-keyword=Speciation en-keyword=Sulawesi kn-keyword=Sulawesi END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=1 article-no= start-page=407 end-page=414 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Polymeric Formula on Outcomes in Robotic Pancreatectomy: A Randomized Controlled Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Evidence regarding the benefits of nutritional therapy after robotic pancreatectomy is limited. This randomized controlled trial aimed to investigate the effects of a polymeric formula (PF) on preventing body weight loss (BWL) following robotic pancreatectomy.
Patients and Methods: This single-center, open-label, randomized trial was conducted to assign 46 patients undergoing robotic pancreatectomy in a 1:1 ratio to either the PF (ISOCAL Clear) or control group. The primary endpoint was the percentage of BWL on postoperative days 14 and 28. The secondary endpoints were postoperative outcomes.
Results: Of the 52 eligible patients between December 2023 and November 2024, 46 were analyzed using intention-to-treat principles: 23 in the ISOCAL group and 23 in the control group. The %BWL was significantly lower in the ISOCAL group compared with that in the control group on postoperative days 14 (4.8±3.5% vs. 6.6±3.2%, p=0.02) and 28 (6.4±3.0% vs. 8.4±3.5%, p=0.047). Postoperative outcomes, including major complications (p=0.55) and hospital stay (p=0.83), did not differ significantly between the groups.
Conclusion: This study demonstrates the safety and feasibility of administering PF to patients undergoing robotic pancreatectomy. The results showed the beneficial effects of PF on mitigating BWL without compromising short-term 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=YAMADAMOTOHIKO en-aut-sei=YAMADA en-aut-mei=MOTOHIKO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NISHIYAMATAKEYOSHI en-aut-sei=NISHIYAMA en-aut-mei=TAKEYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NAGAIYASUO en-aut-sei=NAGAI en-aut-mei=YASUO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HASHIMOTOMASASHI en-aut-sei=HASHIMOTO en-aut-mei=MASASHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=FUJIWARATOSHIYOSHI en-aut-sei=FUJIWARA en-aut-mei=TOSHIYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Robotic pancreatectomy kn-keyword=Robotic pancreatectomy en-keyword=nutrition kn-keyword=nutrition en-keyword=polymeric formula kn-keyword=polymeric formula en-keyword=outcomes kn-keyword=outcomes 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=166 cd-vols= no-issue= article-no= start-page=108524 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=eConsult in infectious diseases: A narrative review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Asynchronous electronic consultation, eConsult, is increasingly applied in infectious diseases (ID) management to improve access to specialty care and reduce unnecessary referrals. We aimed to integrate published studies to provide a comparative perspective and propose future directions for ID eConsult.
Methods: To synthesize relevant findings and present a comprehensive overview of ID eConsult, we searched in MEDLINE database and identified 11 studies between 2017 and 2025 on ID eConsult programs. Structured data were extracted on study characteristics, mode of consultation, and outcomes.
Results: Nine studies on outpatient ID eConsult demonstrated faster turnaround times, high rates of avoidance of in-person referrals (24-87%), improved antimicrobial optimization, and high provider satisfaction. Two studies on inpatient ID eConsult reported reductions in mortality, readmission rates, and broad-spectrum antibiotic use.
Conclusions: Given its affordability and scalability, the ID eConsult model is particularly advantageous in resource-limited environments. Collectively, ID eConsult may replace traditional telephone or face-to-face consultations, reducing the need for informal curbside discussions. en-copyright= kn-copyright= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AkazawaHidemasa en-aut-sei=Akazawa en-aut-mei=Hidemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=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= 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= en-keyword=Electronic consultation (eConsult) kn-keyword=Electronic consultation (eConsult) en-keyword=Telehealth kn-keyword=Telehealth en-keyword=Infectious diseases kn-keyword=Infectious diseases en-keyword=Antimicrobial stewardship kn-keyword=Antimicrobial stewardship en-keyword=Primary care kn-keyword=Primary care en-keyword=Remote consultation kn-keyword=Remote consultation 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=26 cd-vols= no-issue=1 article-no= start-page=329 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260131 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High-risk soft-tissue sarcomas in elderly patients: does perioperative radiotherapy improve local control and prognosis? en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims Accumulating evidence suggests that advanced age is associated with poor local control and prognosis in patients with soft-tissue sarcomas (STSs), highlighting the need to optimise treatment for this age group. However, real-world data on treatment details and outcomes in elderly patients are limited. This study aimed to clarify the role of perioperative radiotherapy (RT) for treating high-risk STSs in elderly patients.
Methods Patients aged???70 years who underwent surgery for localised, high-grade, deep-seated non-small round cell STSs measuring???5 cm were included in the Bone and Soft Tissue Tumour Registry in Japan. Patients with small-round cell STSs or myxoid liposarcomas, or those who received perioperative chemotherapy or intraoperative RT, were excluded.
Results Among the 1,214 patients who met the criteria, 47 (4%), 219 (18%), and 2 (0.2%) received neoadjuvant, adjuvant, and both neoadjuvant and adjuvant RT, respectively. The 5- and 10-year disease-specific survival (DSS) rates were 72.7% and 64.7%, respectively. Tumour size???10 cm, intralesional margin, and local recurrence were associated with poorer DSS; however, perioperative RT did not affect DSS. The 5- and 10-year cumulative probabilities of local recurrence (LR) were 14.6% and 19.5%, respectively. Trunk wall tumours, dedifferentiated liposarcomas, marginal margins, and intralesional margins were associated with a higher probability of LR. Adjuvant RT was associated with a reduced LR probability in patients with intralesional (p = 0.005) or marginal margins (p?=?0.044); however, no such benefit was observed in patients with wide margins, who constituted the majority of the cohort, resulting in no significant association between perioperative RT and LR in overall analyses. In the propensity score-matched cohort, no significant differences in DSS or cumulative probability of LR were observed between patients with and without perioperative RT.
Conclusion Adjuvant RT was associated with reduced LR rates in elderly patients with high-risk STSs who had intralesional or marginal margins. However, because most patients achieved wide margins and no benefit of perioperative RT was observed in this group, RT was not associated with reduced LR or improved survival in the overall or propensity score?matched analyses. Prospective trials are warranted to define the role of perioperative RT in elderly patients with high-risk STSs. en-copyright= kn-copyright= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro 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=NezuYutaka en-aut-sei=Nezu en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TajimaTakashi en-aut-sei=Tajima en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiwaShinji en-aut-sei=Miwa en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KojimaToshio en-aut-sei=Kojima en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiwaraShuichi en-aut-sei=Fujiwara en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Centre for Innovative Clinical Medicine, Medical Development Field, Okayama University kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Yokohama City University kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Kyorin University Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Nihon University School of Medicine kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Musculoskeletal Oncology, National Cancer Centre Hospital kn-affil= affil-num=9 en-affil=Department of Advanced Medical Sciences, Oita University Faculty of Medicine kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Soft-tissue sarcoma kn-keyword=Soft-tissue sarcoma en-keyword=High-risk kn-keyword=High-risk en-keyword=Surgery kn-keyword=Surgery en-keyword=Perioperative radiotherapy kn-keyword=Perioperative radiotherapy en-keyword=Elderly patients kn-keyword=Elderly patients END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=2 article-no= start-page=832 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Possible Involvement of Hypothalamic Dysfunction in Long COVID Patients Characterized by Delayed Response to Gonadotropin-Releasing Hormone en-subtitle= kn-subtitle= en-abstract= kn-abstract=Long COVID (LC) may involve endocrine dysfunction; however, the underlying mechanism remains unclear. To examine hypothalamic?pituitary responses in patients with LC, we conducted a single-center retrospective study of patients with refractory LC referred to our University Hospital who underwent anterior pituitary stimulation tests. Between February 2021 and November 2025, 1251 patients with long COVID were evaluated, of whom 207 (19%) had relatively low random ACTH or cortisol levels. Ultimately, 16 underwent anterior pituitary stimulation tests and were included. All tests were performed in an inpatient setting without exogenous steroids. Fifteen patients (six women, mean age 35.6 years) underwent corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone (GnRH) tests. All patients had mild acute COVID-19, eight had ?2 vaccinations, and the mean interval from infection was 343 days. Frequent symptoms included fatigue (100%), insomnia (66.7%), headache (60.0%), anorexia/nausea (40.0%), and brain fog (40.0%). Mean early-morning cortisol and 24 h urinary free cortisol were 7.5 μg/dL and 41.0 μg/day, respectively. MRI showed an empty sella in one case. Peak hormonal responses were preserved (ΔACTH 247%, ΔTSH 918%, ΔPRL 820%, ΔFSH 187%, ΔLH 1150%); however, peaks were delayed beyond 60 min in ACTH (13%), LH (33%), and FSH (87%). Notably, significantly delayed elevations remained at 120 min in the responses of TSH (4.1-fold), PRL (1.8-fold), LH (9.3-fold), and FSH (2.8-fold), suggesting possible hypothalamic involvement, particularly in the gonadotropin responses. Additionally, serum IGF-I was lowered (?0.70 SD), while GH response (mean peak 35.5 ng/mL) was preserved by growth hormone-releasing peptide (GHRP)-2 stimulation. Low-dose hydrocortisone and testosterone were initiated for three patients. Although direct viral effects and secondary suppression have been proposed, our findings may suggest that, at least in part, the observed response characteristics are consistent with functional secondary hypothalamic dysfunction rather than irreversible primary injury. These findings highlight the need for objective endocrine evaluation before initiating hormone replacements. en-copyright= kn-copyright= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki 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=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=SuyamaAtsuhito en-aut-sei=Suyama en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakaseRyosuke en-aut-sei=Takase en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MasudaYohei en-aut-sei=Masuda en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OmuraDaisuke en-aut-sei=Omura en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakuradaYasue en-aut-sei=Sakurada en-aut-mei=Yasue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsudaYui en-aut-sei=Matsuda en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HasegawaToru en-aut-sei=Hasegawa en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HondaHiroyuki en-aut-sei=Honda en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=UedaKeigo en-aut-sei=Ueda en-aut-mei=Keigo 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 General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=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=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=COVID-19 kn-keyword=COVID-19 en-keyword=gonadotropin kn-keyword=gonadotropin en-keyword=gonadotropin-releasing hormone (GnRH) kn-keyword=gonadotropin-releasing hormone (GnRH) en-keyword=hypothalamus kn-keyword=hypothalamus en-keyword=long COVID kn-keyword=long COVID END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=4 article-no= start-page=728 end-page=741 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=Constitutive EGFR Activation Induced by PTPRR Downregulation Confers Resistance to KRAS Inhibitors en-subtitle= kn-subtitle= en-abstract= kn-abstract=KRASG12C inhibitors, such as sotorasib, show clinical efficacy for non?small cell lung cancer (NSCLC) positive for the G12C mutations of KRAS, but primary and acquired resistance to these drugs remains a clinical problem. In this study, we show that the development of resistance to sotorasib in KRASG12C-positive NSCLC cells was mediated by constitutive activation of EGFR resulting from downregulation of the protein tyrosine phosphatase receptor type R (PTPRR). PTPRR has been identified as a physiologic regulator of ERK signaling in several cancer types. In our study, PTPRR was demonstrated to bind directly to EGFR, facilitating its dephosphorylation on tyrosine residues. Resumption of PTPRR expression in the resistant cells attenuated EGFR phosphorylation and restored sotorasib sensitivity. PTPRR downregulation was associated with gene promoter hypermethylation in the sotorasib-resistant cells and NSCLC tissue samples. Furthermore, low PTPRR expression in tumor specimens was associated with shorter progression-free and overall survival for patients with NSCLC treated with sotorasib. In contrast to sotorasib, high PTPRR expression was associated with a poor response to EGFR tyrosine kinase inhibitors in EGFR-mutated NSCLC, suggesting that PTPRR may broadly regulate EGFR dependence in NSCLC. Finally, dual blockade of KRASG12C and EGFR showed a substantial antitumor effect in a xenograft model of sotorasib-resistant NSCLC. This approach is therefore a rational therapeutic strategy for KRASG12C-positive NSCLC, especially for tumors showing PTPRR downregulation.
Significance: The current study shows that downregulation of PTPRR induces EGFR activation and resistance to KRASG12C inhibitors in NSCLC, suggesting dual KRAS-EGFR blockade as a rational therapy. PTPRR may help identify patient subgroups that would benefit from the addition of EGFR inhibitors to KRASG12C-targeted therapies. en-copyright= kn-copyright= en-aut-name=KanemuraHiroaki en-aut-sei=Kanemura en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeharaToshiyuki en-aut-sei=Takehara en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaenishiOsamu en-aut-sei=Maenishi en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwawakiNatsumi en-aut-sei=Iwawaki en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KunimasaKei en-aut-sei=Kunimasa en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakayamaTomohiro en-aut-sei=Nakayama en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeSatomi en-aut-sei=Watanabe en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SuzukiShinichiro en-aut-sei=Suzuki en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakaiKazuko en-aut-sei=Sakai en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=KudoKeita en-aut-sei=Kudo en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NishioKazuto en-aut-sei=Nishio en-aut-mei=Kazuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakagawaKazuhiko en-aut-sei=Nakagawa en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HayashiHidetoshi en-aut-sei=Hayashi en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TeramuraTakeshi en-aut-sei=Teramura en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= affil-num=1 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=2 en-affil=Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Pathology, Kindai University Faculty of Medicine kn-affil= affil-num=4 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine kn-affil= affil-num=6 en-affil=Department of Thoracic Oncology, Osaka International Cancer Institute kn-affil= affil-num=7 en-affil=Department of Medical Oncology, Kishiwada City Hospital kn-affil= affil-num=8 en-affil=Department of Medical Oncology, Kishiwada City Hospital kn-affil= affil-num=9 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=10 en-affil=Department of Genome Biology, Kindai University Faculty of Medicine kn-affil= affil-num=11 en-affil=Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine kn-affil= affil-num=12 en-affil=Department of Medical Oncology, National Hospital Organization Osaka Minami Medical Center kn-affil= affil-num=13 en-affil=Department of Genome Biology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=15 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=16 en-affil=Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine kn-affil= affil-num=17 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine 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) ?, c = 32.4870(3) ?). 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=370 cd-vols= no-issue= article-no= start-page=199761 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=Toward in planta studies of persistent fungal viruses in a model plant en-subtitle= kn-subtitle= en-abstract= kn-abstract=A model plant, Nicotiana benthamiana, was examined as a host for persistent fungal viruses capable of crossing organismal kingdoms. Protoplasts of N. benthamiana were transfected with a mixture of virions of a betapartitivirus, Rosellinia necatrix partitivirus 18 (RnPV18), and an alphapartitivirus, RnPV19, and were then subjected to plantlet regeneration. Primary RT-PCR-based screening showed that nearly 100% of the resulting calli tested positive for RnPV18, whereas approximately 90% were positive for RnPV19. However, secondary screening performed at a later stage of tissue culture revealed that only 6% of the calli retained RnPV19, whereas approximately 33% retained RnPV18. These results suggest that the calli were chimeric, consisting of virus-infected and virus-free sectors, and that the partitiviruses were progressively lost during callus maintenance. It is also possible that these fungal partitiviruses were unable to fully adapt to, or counteract, host defense responses sufficiently to establish stable infection. We succeeded in obtaining RnPV18-positive calli and suspension cultures that maintained the virus at detectable levels, as shown by northern blotting, after prolonged subculture for at least 9 months. High-throughput small RNA analyses revealed both similarities and differences in virus-derived small RNA profiles among protoplasts, calli, and suspension cultures. Viral genome analyses further revealed developmental stage-specific and stage-independent substitutions compared with the RnPV18 genomic sequence maintained in the original fungal host. Interestingly, a C-to-U mutation in the RNA-dependent RNA polymerase-encoding region of RnPV18 was detected much more frequently in a particular line, designated B21, than in another stably RnPV18-infected line, P8, irrespective of whether the virus was maintained in suspension cultures or calli. This may explain why virus accumulation in B21 calli and suspension cultures was much lower than that in P8 cell cultures, as RNA-seq analyses showed 159 K counts per million for P8 versus 44 K counts per million for B21. Taken together, this study provides a platform for investigating partitiviruses and other ubiquitous persistent viruses, which are generally difficult to inoculate experimentally. en-copyright= kn-copyright= en-aut-name=TelengechPaul en-aut-sei=Telengech en-aut-mei=Paul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=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=FavarettoFrancesco en-aut-sei=Favaretto en-aut-mei=Francesco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IchikawaHiroaki en-aut-sei=Ichikawa en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaruyamaKazuyuki en-aut-sei=Maruyama en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HyodoKiwamu en-aut-sei=Hyodo en-aut-mei=Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= affil-num=1 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=8 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Cross-kingdom infection kn-keyword=Cross-kingdom infection en-keyword=Tissue culture kn-keyword=Tissue culture en-keyword=Partitivirus kn-keyword=Partitivirus en-keyword=dsRNA virus kn-keyword=dsRNA virus en-keyword=Nicotiana, benthamiana kn-keyword=Nicotiana, benthamiana en-keyword=Callus kn-keyword=Callus en-keyword=Suspension culture kn-keyword=Suspension culture en-keyword=Model plant kn-keyword=Model plant END start-ver=1.4 cd-journal=joma no-vol=408 cd-vols= no-issue= article-no= start-page=117978 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=A flexible PVDF-based galloping flow sensor en-subtitle= kn-subtitle= en-abstract= kn-abstract=Effective monitoring of low flow velocities in small rivers and irrigation channels is hindered by the power requirements and maintenance costs of existing technologies. This study proposes a novel flexible piezoelectric polymer flow sensor utilizing galloping vibration to detect flow velocity in the low range (? 0.1?m/s). The sensor features a flexible cantilever structure composed of a silicone rubber beam embedded with a polyvinylidene fluoride (PVDF) film and a tip pillar. Unlike conventional devices based on flow-induced vibration, the use of low-stiffness materials enables the induction of self-excited vibration even under weak fluid forces. Computational fluid dynamics (CFD) analysis has been conducted to optimize the tip shape; a D-shaped semicylinder is selected over a cylinder and a square prism because the geometry maximizes the lift force per unit mass, ensuring efficient energy conversion. To predict sensor behavior, a coupled mechanical-fluid-electrical model was developed. Specifically, the model accounts for the static deflection angle caused by fluid drag. Water channel experiments demonstrated that sensors with beam thicknesses under 4?mm successfully generated stable periodic outputs at 0.1?m/s, a regime previously difficult for galloping-based devices. Conversely, thicker beam which has a thickness of 8?mm achieved higher outputs at higher velocities but failed to actuate at low speeds. Furthermore, the study showed a vibration suppression phenomenon in flexible beams at high flow velocities due to excessive static deflection, which was accurately reproduced by the analytical model. These findings establish structural stiffness as the critical design parameter for optimizing the operable velocity range of flow sensors. en-copyright= kn-copyright= en-aut-name=KuroseMitsuki en-aut-sei=Kurose en-aut-mei=Mitsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=SatoYuya en-aut-sei=Sato en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=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=HiejimaShinji en-aut-sei=Hiejima en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UedaTakeji en-aut-sei=Ueda en-aut-mei=Takeji 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=Hydro-VENUS Co., Ltd., Okayama University kn-affil= en-keyword=Flow velocity sensor kn-keyword=Flow velocity sensor en-keyword=Piezoelectric polymer kn-keyword=Piezoelectric polymer en-keyword=Flow induced vibration kn-keyword=Flow induced vibration en-keyword=Galloping vibration kn-keyword=Galloping vibration 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= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Uniqueness of Dirichlet forms for random point fields in the absence of tail triviality en-subtitle= kn-subtitle= en-abstract= kn-abstract=We consider an infinite system of interacting Brownian motions that preserves a given random point field invariant. Such dynamics are constructed using Dirichlet form theory, which naturally leads to two Dirichlet forms for the random point field: the upper and the lower Dirichlet forms. A fundamental question is the uniqueness of the Dirichlet form: that is, whether these two forms coincide. This uniqueness has often been imposed as a key assumption in the Dirichlet form approach to the stochastic analysis for infinite particle systems. A sufficient condition for the uniqueness of the Dirichlet forms is known when the random point field is tail trivial. However, tail triviality has been established for only a limited class of random point fields. In this paper, we prove the uniqueness of the Dirichlet form without assuming tail triviality. The main contribution of this work is to establish the tail preserving property, which asserts that global properties of the system, such as particle density, are preserved under time evolution. As a consequence, our results also imply the strong uniqueness of solutions to the associated infinite-dimensional stochastic differential equations. en-copyright= kn-copyright= en-aut-name=KawamotoYosuke en-aut-sei=Kawamoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama university kn-affil= en-keyword=Infinite particle systems kn-keyword=Infinite particle systems en-keyword=Interacting Brownian motions kn-keyword=Interacting Brownian motions en-keyword=Uniqueness of Dirichlet forms kn-keyword=Uniqueness of Dirichlet forms en-keyword=Random matrices kn-keyword=Random matrices END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=1 article-no= start-page=94 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Three-dimensional virtual planning reduces operative time in orthognathic surgery: a procedure-specific retrospective study incorporating additive manufacturing en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Three-dimensional virtual surgical planning (3D-VSP) is increasingly used in orthognathic surgery; however, procedure-specific evidence regarding its real-world impact on operative efficiency and intraoperative blood loss remains limited. This study evaluated the association between 3D-VSP implementation and operative time, and intraoperative blood loss across different orthognathic procedures.
Methods This retrospective cohort study included consecutive patients who underwent orthognathic surgery at a single academic institution before (2019?2020) and after (2023?2024) the full implementation of 3D-VSP integrated with in-house additive manufacturing (n?=?344). Procedure-specific multivariable linear regression analyses were performed, adjusting for age, sex, and surgeon experience.
Results After 3D-VSP implementation, operative time was reduced by approximately 36 min in sagittal split ramus osteotomy (SSRO), 50 min in Le Fort I (LF1) combined with SSRO, and 42 min in segmental LF1 combined with SSRO, representing a 15?20% reduction in total operative time. No meaningful reduction was observed in intraoral vertical ramus osteotomy (IVRO)-based procedures. A statistically significant, but modest, reduction in intraoperative blood loss was observed only in SSRO. The time-saving effect was independent of surgeon experience.
Conclusion The clinical benefit of 3D-VSP in orthognathic surgery is procedure-dependent and most evident in geometrically complex SSRO-based operations. These findings support the targeted implementation of digital planning and additive manufacturing workflows to improve operative efficiency in routine practice. en-copyright= kn-copyright= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshiokaNorie en-aut-sei=Yoshioka en-aut-mei=Norie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiyamaAkiyoshi en-aut-sei=Nishiyama en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MasuiMasanori en-aut-sei=Masui en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=TakakuraHiroaki en-aut-sei=Takakura en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=OnoKisho en-aut-sei=Ono en-aut-mei=Kisho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Orthognathic surgery kn-keyword=Orthognathic surgery en-keyword=Surgical planning kn-keyword=Surgical planning en-keyword=Three-dimensional virtual surgical planning kn-keyword=Three-dimensional virtual surgical planning en-keyword=Operative time kn-keyword=Operative time en-keyword=Intraoperative blood loss kn-keyword=Intraoperative blood loss en-keyword=Additive manufacturing kn-keyword=Additive manufacturing en-keyword=Sagittal split ramus osteotomy kn-keyword=Sagittal split ramus osteotomy END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=6 article-no= start-page=e0350803 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A multicenter, randomized, parallel-group confirmatory study protocol to evaluate the efficacy of Soft Protector CPC, a novel oral mucosal protectant, in preventing oral mucositis and alleviating pain in patients with breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oral mucositis is a frequent and debilitating adverse event observed in patients undergoing chemotherapy or radiotherapy. Current management strategies are limited in duration, require frequent application, and fail to address the mechanical irritation from teeth. A novel device, Soft Protector CPC, was developed to overcome these limitations. This multicenter, randomized, two-arm, open-label, confirmatory trial aims to evaluate the efficacy and safety of Soft Protector CPC in patients with breast cancer undergoing chemotherapy. A total of 154 participants will be randomly assigned in a 1:1 ratio to receive either oral care with Soft Protector CPC or oral care alone. The primary endpoint will be oral mucositis as assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 during the comparative treatment period. The secondary endpoints will include CTCAE v3.0 during the continuous treatment period, oral mucositis, pain (CTCAE v5.0), quality of life (Patient Reported Outcomes-CTCAE version 1.0 [PRO-CTCAE v1.0], the 15-item oral health questionnaire of the European Organization For Research And Treatment Of Cancer [EORTC QLQ-OH15], and the pain Numeric Rating Scale), onset and site of mucositis, completion of chemotherapy, use of rescue medications, technical feasibility, and patient preference. The safety endpoints will include adverse events, device malfunction, and laboratory tests. This trial is expected to establish the clinical utility of the Soft Protector CPC for the prevention and management of oral mucositis, with the potential to improve the patients’ quality of life and adherence to cancer therapy. This study was approved by the Clinical Research Review Board and registered with the Japan Registry of Clinical Trials, jRCTs062250005, on April 18, 2025. en-copyright= kn-copyright= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FurukawaKohei en-aut-sei=Furukawa en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UsubuchiMasatoshi en-aut-sei=Usubuchi en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HamadaTomofumi en-aut-sei=Hamada en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=YoshidaMichihiro en-aut-sei=Yoshida en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakatsukaYuki en-aut-sei=Nakatsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Dentistry and Oral Surgery, Shikoku Cancer Center kn-affil= affil-num=3 en-affil=Department of Dentistry, Miyagi Cancer Center kn-affil= affil-num=4 en-affil=Department of Dentistry and Oral Surgery, Sagara Hospital kn-affil= affil-num=5 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= 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=53 cd-vols= no-issue=2 article-no= start-page=e2025GL118147 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260113 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Davemaoite Elasticity Reveals Slab‐Induced Heterogeneity in the Mantle Transition Zone en-subtitle= kn-subtitle= en-abstract= kn-abstract=The observed 2%?7% low-shear velocity (VS) anomalies near the subducted slab at the bottom mantle transition zone (MTZ) indicate strong lateral heterogeneity, which is commonly attributed to subducted oceanic crust. However, davemaoite, a major constituent of the subducted oceanic crust, has been poorly constrained in its elasticity, hindering accurate velocity modeling and obscuring the origin of these low-velocity features. Here we report single-crystal elasticity of Ti-bearing davemaoite with the composition of Ca(Si0.57Ti0.43)O3 under high pressure-temperature and found that Ti incorporation significantly reduces velocities and alters the pressure dependence of the shear modulus. Further velocity modeling demonstrated that subducted crusts with varying Ti content have seismic signatures of 1.7(2)?6.8(5)% low-VS at the bottom MTZ, consistent with the observed low-VS structure in the region. These findings highlight the role of slab-derived chemical heterogeneity in generating mantle seismic anomalies and provide new experimental constraints on the structure and dynamics of the deep Earth. en-copyright= kn-copyright= en-aut-name=YuYingxin en-aut-sei=Yu en-aut-mei=Yingxin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZhangXinyue en-aut-sei=Zhang en-aut-mei=Xinyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=LiLuo en-aut-sei=Li en-aut-mei=Luo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaoZhu en-aut-sei=Mao en-aut-mei=Zhu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SunNingyu en-aut-sei=Sun en-aut-mei=Ningyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WangDenglei en-aut-sei=Wang en-aut-mei=Denglei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LiJing en-aut-sei=Li en-aut-mei=Jing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ZhaoChaoshuai en-aut-sei=Zhao en-aut-mei=Chaoshuai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=QianCheng en-aut-sei=Qian en-aut-mei=Cheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WeiYingzhan en-aut-sei=Wei en-aut-mei=Yingzhan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=LiXinyang en-aut-sei=Li en-aut-mei=Xinyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WangYuzhu en-aut-sei=Wang en-aut-mei=Yuzhu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= affil-num=1 en-affil=State Key Laboratory of Precision Geodesy, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= affil-num=2 en-affil=State Key Laboratory of Precision Geodesy, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= affil-num=3 en-affil=GeoSoilEnviroCARS, University of Chicago kn-affil= affil-num=4 en-affil=State Key Laboratory of Precision Geodesy, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= affil-num=5 en-affil=State Key Laboratory of Precision Geodesy, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= affil-num=6 en-affil=State Key Laboratory of Precision Geodesy, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= affil-num=7 en-affil=State Key Laboratory of Precision Geodesy, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= affil-num=8 en-affil=State Key Laboratory of Precision Geodesy, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= affil-num=9 en-affil=State Key Laboratory of Precision Geodesy, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= affil-num=10 en-affil=State Key Laboratory of Geological Processes and Mineral Resources, China University of Geosciences kn-affil= affil-num=11 en-affil=State Key Laboratory of High Pressure and Superhard Materials, College of Physics, Jilin University kn-affil= affil-num=12 en-affil=State Key Laboratory of High Pressure and Superhard Materials, College of Physics, Jilin University kn-affil= affil-num=13 en-affil=Shanghai Advanced Research Institute, Chinese Academy of Sciences kn-affil= affil-num=14 en-affil=Institute for Planetary Materials, Okayama University kn-affil= en-keyword=Ti-bearing davemaoite kn-keyword=Ti-bearing davemaoite en-keyword=single-crystal elasticity kn-keyword=single-crystal elasticity en-keyword=slab-induced heterogeneity kn-keyword=slab-induced heterogeneity en-keyword=mantle transition zone kn-keyword=mantle transition zone END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue= article-no= start-page=1850114 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260529 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bee larvae ameliorate andropause-like symptoms via a hormone-independent, antioxidant mechanism en-subtitle= kn-subtitle= en-abstract= kn-abstract=Late-onset hypogonadism (LOH), also known as the male menopause, is characterized by a decline in sexual function as well as various physical and psychological symptoms, including anxiety. Although bee larvae have historically been utilized as a traditional food and medicine, their efficacy and physiological mechanisms of action against male menopausal symptoms remain unclear. In this study, we investigated the effects of bee larvae (BL) on sexual and anxiety-like behaviors using two rodent models of the male menopause: aged rats and castrated mice. In the aged rat model (64 weeks old), dietary BL supplementation for 4 weeks significantly attenuated the age-associated decline in ejaculation frequency compared to controls, while no significant effects were observed on mount or intromission frequencies. Notably, plasma analysis revealed no significant differences in testosterone or dihydrotestosterone levels between the BL and control groups. To elucidate the underlying mechanism, we evaluated sexual function using a castrated mouse model. While BL supplementation did not affect sexual behavior in intact mice, post-castration BL treatment significantly shortened intromission latency without altering mount frequency. In the elevated plus maze test, BL significantly alleviated castration-induced anxiety-like behaviors and improved exploratory activity. Furthermore, in vitro assays demonstrated that the BL extract exerts potent protective effects against oxidative stress, a pathological factor contributing to both erectile dysfunction and anxiety. These results suggest that BL improves erectile function and anxiety via hormone-independent mechanisms, potentially by mitigating oxidative stress in vascular and neural tissues. Thus, bee larvae represent a promising functional food for ameliorating the multi-faceted physical and psychological symptoms associated with male menopause. en-copyright= kn-copyright= en-aut-name=ItoTakashi en-aut-sei=Ito en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkumuraNobuaki en-aut-sei=Okumura en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtiTakumi en-aut-sei=Oti en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= affil-num=1 en-affil=Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Institute for Bee Products & Health Science, Yamada Bee Company, Inc. kn-affil= affil-num=3 en-affil=Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=anxiety kn-keyword=anxiety en-keyword=bee larvae kn-keyword=bee larvae en-keyword=late-onset hypogonadism kn-keyword=late-onset hypogonadism en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=sexual behavior kn-keyword=sexual behavior END start-ver=1.4 cd-journal=joma no-vol=130 cd-vols= no-issue=8 article-no= start-page=e2025JB031715 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Linking the Spin Transition of Ferric Iron in δ‐(Al,Fe)OOH to Water Storage in the Lower Mantle en-subtitle= kn-subtitle= en-abstract= kn-abstract=As the most massive geochemical reservoir, the lower mantle affects the Earth's budget of volatile elements, including hydrogen or H2O. The properties of minerals in the lower mantle are further affected by changes in the electronic configurations of iron cations, that is, by spin transitions. The feedback between spin transitions and potential storage of H2O in solid hydrous phases in the lower mantle, however, remains unexplored. By combining high-pressure nuclear resonant inelastic X-ray scattering and high-pressure high-temperature X-ray diffraction experiments, we constrained the thermal equation of state of δ-(Al,Fe)OOH, a member of the phase H solid solution. Based on the derived thermal equation of state of δ-(Al,Fe)OOH and the underlying thermodynamic model, we calculate the excess Gibbs free energy that arises from the spin transition of ferric iron in this compound and evaluate the effect on phase equilibria. The results of our analysis show that the spin transition of ferric iron in phase H may significantly reduce the thermodynamic activity and hence the concentration of H2O in a coexisting hydrous melt. As a consequence, nominally anhydrous minerals of the lower mantle may become dehydrated in the presence of phase H. Our analysis further suggests that, under certain conditions, the spin transition may expand the thermal stability of Fe3+-bearing phase H and create a geochemical link between the storage of H2O in phase H and ferric iron in the lower mantle. en-copyright= kn-copyright= en-aut-name=BuchenJohannes en-aut-sei=Buchen en-aut-mei=Johannes kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PardoOlivia S. en-aut-sei=Pardo en-aut-mei=Olivia S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DobrosavljevicVasilije V. en-aut-sei=Dobrosavljevic en-aut-mei=Vasilije V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SturhahnWolfgang en-aut-sei=Sturhahn en-aut-mei=Wolfgang 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=CharitonStella en-aut-sei=Chariton en-aut-mei=Stella kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GreenbergEran en-aut-sei=Greenberg en-aut-mei=Eran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ToellnerThomas S. en-aut-sei=Toellner en-aut-mei=Thomas S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=JacksonJennifer M. en-aut-sei=Jackson en-aut-mei=Jennifer M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Bayerisches Geoinstitut, Universit?t Bayreuth kn-affil= affil-num=2 en-affil=Seismological Laboratory, California Institute of Technology kn-affil= affil-num=3 en-affil=Seismological Laboratory, California Institute of Technology kn-affil= affil-num=4 en-affil=Seismological Laboratory, California Institute of Technology kn-affil= affil-num=5 en-affil=Now at Institute for Planetary Materials, Okayama University kn-affil= affil-num=6 en-affil=GSECARS, The University of Chicago kn-affil= affil-num=7 en-affil=GSECARS, The University of Chicago kn-affil= affil-num=8 en-affil=Advanced Photon Source, Argonne National Laboratory kn-affil= affil-num=9 en-affil=Seismological Laboratory, California Institute of Technology kn-affil= en-keyword=spin transition kn-keyword=spin transition en-keyword=phase H kn-keyword=phase H en-keyword=lower mantle kn-keyword=lower mantle en-keyword=high pressure kn-keyword=high pressure en-keyword=equation of state kn-keyword=equation of state en-keyword=phonon density of states kn-keyword=phonon density of states 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=胸腺癌患者における全胸腺摘出術は部分胸腺摘出術よりも腫瘍学的に優れている：多施設共同実臨床データ解析からの知見 kn-title=Total Thymectomy Is Oncologically Superior to Partial Thymectomy in Patients with Thymic Carcinoma: Insights from a Multicenter Real World Data Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HAYASHITatsuya en-aut-sei=HAYASHI en-aut-mei=Tatsuya kn-aut-name=林龍也 kn-aut-sei=林 kn-aut-mei=龍也 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=予期せぬ N1/N2 リンパ節転移を伴う非小細胞肺癌に対する区域切除と葉切除の臨床成績比較：多施設リアルワールドデータ研究 kn-title=Comparable Clinical Outcomes Between Segmentectomy and Lobectomy for NSCLC With Unsuspected N1/N2: A Multicenter Real-World Data Study en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=RYUKOTsuyoshi en-aut-sei=RYUKO en-aut-mei=Tsuyoshi kn-aut-name=柳光剛志 kn-aut-sei=柳光 kn-aut-mei=剛志 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=FAP標的近赤外光免疫療法による薬剤送達の増強 kn-title=Enhancement of drug delivery through fibroblast activation protein-targeted near-infrared photoimmunotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NISHIMURASeitaro en-aut-sei=NISHIMURA en-aut-mei=Seitaro kn-aut-name=西村星多郎 kn-aut-sei=西村 kn-aut-mei=星多郎 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=ダパグリフロジンによるアデノシン介在性好中球浸潤抑制は腎虚血再灌流障害を減弱化する：リアルタイムイメージングとメタボローム解析を用いた研究 kn-title=Adenosine-mediated Neutrophil Regulation by Dapagliflozin Attenuates Renal Ischemia/Reperfusion Injury: Real-time Imaging and Metabolic Insights en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YAMANOITomoaki en-aut-sei=YAMANOI en-aut-mei=Tomoaki kn-aut-name=山野井友昭 kn-aut-sei=山野井 kn-aut-mei=友昭 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=マウス脳卒中モデルにおけるトランザクティブ応答DNA結合タンパク質43kDaを維持する潜在的メカニズム kn-title=The potential mechanism maintaining transactive response DNA binding protein 43 kDa in the mouse stroke model en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=BIANYUTING en-aut-sei=BIAN en-aut-mei=YUTING kn-aut-name=卞宇? kn-aut-sei=卞 kn-aut-mei=宇? 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=ヒアルロン酸ナトリウムとカルボキシメチルセルロースからなる生体吸収性膜（セプラフィルム）は、腹膜3Dモデルおよびマウスモデルにおいて腹膜欠損部への癌細胞転移を抑制する kn-title=Bioresorbable Membrane Composed of Sodium Hyaluronate and Carboxymethylcellulose (Seprafilm) Prevents Cancer Implantation at Peritoneal Defects in 3D‐Peritoneum and Murine Models en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=UNEYuta en-aut-sei=UNE en-aut-mei=Yuta kn-aut-name=宇根悠太 kn-aut-sei=宇根 kn-aut-mei=悠太 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=効率的な時空間洪水予測に向けた氾濫解析結果を活用したランダムフォレスト手法の開発 kn-title=Development of a Hydrodynamic-Simulation-Informed Random Forest Method for Efficient Spatiotemporal Flood Prediction en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=LIUKEXIN en-aut-sei=LIU en-aut-mei=KEXIN kn-aut-name=劉可欣 kn-aut-sei=劉 kn-aut-mei=可欣 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil=岡山大学大学院環境生命自然科学研究科 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=マウスモデルにおける枯草菌（Bacillus subtilis）による歯周炎への影響 kn-title=Effects of Bacillus subtilis on Periodontitis in a Mouse Model en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ZHANGYIXUAN en-aut-sei=ZHANG en-aut-mei=YIXUAN kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= 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=ラット歯周炎モデルにおけるmiR-128-3pによる腎臓の炎症への影響 kn-title=Effects of miR-128-3p on Renal Inflammation in a Rat Periodontitis Model en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MOHAMMAD NURHAMIM en-aut-sei=MOHAMMAD NURHAMIM 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=患者由来癌関連線維芽細胞を用いた三次元モデルに対するホウ素中性子捕捉療法の評価 kn-title=Assessment of Boron Neutron Capture Therapy on Three Dimensional Model of Patient-Derived Cancer-Associated Fibroblasts and Oral Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HARAIzumi en-aut-sei=HARA en-aut-mei=Izumi kn-aut-name=原和泉 kn-aut-sei=原 kn-aut-mei=和泉 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=14 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ibuprofen gargle for quality of life and pain improvement in oral lichen planus: randomized crossover and long-term extension phase II study en-subtitle= kn-subtitle= en-abstract= kn-abstract= 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=KakeiYasumasa en-aut-sei=Kakei en-aut-mei=Yasumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IoroiTakeshi en-aut-sei=Ioroi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YatagaiNanae en-aut-sei=Yatagai en-aut-mei=Nanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KashinMasahiko en-aut-sei=Kashin en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiMasaki en-aut-sei=Kobayashi en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MoriokaAsami en-aut-sei=Morioka en-aut-mei=Asami 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=HasegawaTakumi en-aut-sei=Hasegawa en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkashiMasaya en-aut-sei=Akashi en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine 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 Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= en-keyword=Oral lichen planus kn-keyword=Oral lichen planus en-keyword=Ibuprofen gargle kn-keyword=Ibuprofen gargle en-keyword=PROMS kn-keyword=PROMS en-keyword=Oral pain kn-keyword=Oral pain en-keyword=Long-term extension study kn-keyword=Long-term extension study END start-ver=1.4 cd-journal=joma no-vol=302 cd-vols= no-issue=6 article-no= start-page=113085 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=A photoactivatable Cre-loxP system for spatiotemporal genetic manipulation in mouse taste buds en-subtitle= kn-subtitle= en-abstract= kn-abstract=Conventional genetic approaches, including global gene KO and conditional KO strategies such as the Cre-loxP system, have some limitations arising from systemic effects or insufficient temporal resolution. The recently developed photoactivatable Cre (PA-Cre) system may have a potential to improve spatiotemporal control of gene manipulation. In this study, we established and validated the feasibility of the PA-Cre system using taste buds as a model. We generated TRE-PA-Cre:R26-rtTA/tdTomato mice to evaluate blue-light-induced Cre recombinase activity. Through systematic optimization of illumination parameters, we found that a single session of blue-light-illumination resulted in limited recombination efficiency, whereas a multisession illumination strategy markedly increased recombination efficiency. To further assess the utility of the PA-Cre system for gene KO, we generated TRE-PA-Cre:R26-rtTA:Tas1r3-flox mice and targeted a taste-related gene Tas1r3. Genomic DNA quantitative PCR and reverse transcription-quantitative PCR both showed partial reductions in Tas1r3 at the DNA and mRNA levels, respectively. Behavioral assays further revealed a selective decrease in sensitivity to sweet and umami stimuli. Together, these findings demonstrate PA-Cre-mediated gene manipulation in taste buds and establish a practical optical activation paradigm, providing a high-spatiotemporal-resolution tool for investigating gene function in optically targeted regions. en-copyright= kn-copyright= en-aut-name=ZuoYu en-aut-sei=Zuo en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HorieKengo en-aut-sei=Horie en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitohYoshihiro en-aut-sei=Mitoh en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamadaYasuhiro en-aut-sei=Yamada en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakaoTomoka en-aut-sei=Takao en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakaradaTakeshi en-aut-sei=Takarada en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= affil-num=1 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Molecular Pathology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Division of Biochemistry, Kyushu Dental University kn-affil= affil-num=8 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cre-loxP kn-keyword=Cre-loxP en-keyword=genetic manipulation kn-keyword=genetic manipulation en-keyword=mouse kn-keyword=mouse en-keyword=photoactivatable Cre kn-keyword=photoactivatable Cre en-keyword=spatiotemporal kn-keyword=spatiotemporal en-keyword=taste kn-keyword=taste 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= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Incidence of B-cell Malignancies in Patients with Lung Cancer Receiving PD-1 Blockade Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: Many patients with various cancer types have received immune checkpoint inhibitors (ICI) worldwide since their approval, and novel unexpected complications from their long-term use are apparent. We identified some cases of B-cell lymphoma occurring during PD-1 blockade therapy as such unexpected complications. In this study, we aimed to evaluate the incidence of hematologic malignancies in patients with lung cancer receiving PD-1 blockade therapy and to elucidate the mechanisms underlying the progression of these malignancies.
Experimental Design: We performed IHC staining on the clinical samples from patients with B-cell lymphoma that developed during PD-1 blockade therapy and analyzed large-scale real-world datasets. We further investigated the underlying mechanisms through in vitro and in vivo experiments.
Results: A higher incidence of B-cell malignancies has been observed in patients with lung cancer treated with PD-1 blockade therapies based on large-scale real-world data analyses (n = 15,670). The identified lymphomas had a large amount of CD4+ T follicular helper (TFH) cell infiltration. In addition, PD-1 blockade activated PD-1+ TFH cells, which promoted lymphoma proliferation via the IL4/IL4R, IL21/IL21R, and CD40L/CD40 axes. Notably, the lymphomas exhibited high expression of IL4R, IL21R, and CD40.
Conclusions: Our findings highlight the need for careful monitoring and consideration of the potential B-cell malignancy complications in clinical settings in which ICIs are used. en-copyright= kn-copyright= en-aut-name=NinomiyaToshifumi en-aut-sei=Ninomiya en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FangCaiyang en-aut-sei=Fang en-aut-mei=Caiyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorinagaTeruya en-aut-sei=Morinaga en-aut-mei=Teruya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhouWenhao en-aut-sei=Zhou en-aut-mei=Wenhao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MikiSakura en-aut-sei=Miki en-aut-mei=Sakura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ZhuLi en-aut-sei=Zhu en-aut-mei=Li kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 ORCID= en-aut-name=KatsutaTomoya en-aut-sei=Katsuta en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Ohki-IkedaTomoka en-aut-sei=Ohki-Ikeda en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NishiTatsuya en-aut-sei=Nishi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OkamotoIsamu en-aut-sei=Okamoto en-aut-mei=Isamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 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=20 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 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=22 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacy, Okayama University Hospital, Okayama University kn-affil= affil-num=4 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pharmaceutical Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Okayama University Hospital, Okayama University kn-affil= affil-num=13 en-affil=Department of Dermatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Pathology, Okayama University Hospital, Okayama University kn-affil= affil-num=15 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=18 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=19 en-affil=Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=20 en-affil=Department of Pharmacy, Okayama University Hospital, Okayama University kn-affil= affil-num=21 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=22 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=109 cd-vols= no-issue= article-no= start-page=107113 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=Bile acids as candidate therapies for multiple sclerosis: inverse signal analysis using the FDA adverse event reporting system and preclinical validation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Alterations in bile acid metabolism have been observed in individuals with multiple sclerosis (MS), yet the therapeutic implications of bile acid supplementation remain uncertain.
Methods: We conducted a two-stage study integrating pharmacovigilance analysis with preclinical validation to evaluate bile acid derivatives as candidate therapies for MS. A disproportionality analysis of the FDA Adverse Event Reporting System (FAERS; Q4/2003?Q2/2025) was performed to identify inverse associations between MS and bile acid preparations. The effects of ursodeoxycholic acid (UDCA) and obeticholic acid (6-ECDCA) were evaluated in a therapeutic experimental autoimmune encephalomyelitis (EAE) model, with treatment initiated after disease onset.
Results: Among 13,734,539 FAERS reports, 75,659 involved MS. Inverse associations were identified for UDCA (odds ratio [OR]: 0.197, 95% confidence interval [CI]: 0.117?0.333) and 6-ECDCA (OR: 0.128, 95% CI: 0.041?0.396). In the EAE model, UDCA was associated with lower clinical scores at the peak (day 18) and late phases (days 26?28), whereas 6-ECDCA showed only a non-significant trend toward improvement at day 28.
Conclusion: This two-stage investigation highlights the potential utility of pharmacovigilance-guided approaches for identifying therapeutic candidates. Bile acid derivatives, particularly UDCA, are biologically plausible candidates meriting further investigation in the context of MS. en-copyright= kn-copyright= en-aut-name=AsadaMizuho en-aut-sei=Asada en-aut-mei=Mizuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AizawaFuka en-aut-sei=Aizawa en-aut-mei=Fuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MikamiTakahisa en-aut-sei=Mikami en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GodaMitsuhiro en-aut-sei=Goda en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SonodaYuhei en-aut-sei=Sonoda en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NiimuraTakahiro en-aut-sei=Niimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=ChumaMasayuki en-aut-sei=Chuma en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UesawaYoshihiro en-aut-sei=Uesawa en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshizawaKeisuke en-aut-sei=Ishizawa en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Medical Molecular Informatics, Meiji Pharmaceutical University kn-affil= affil-num=2 en-affil=Department of Pharmacy, Tokushima University Hospital kn-affil= affil-num=3 en-affil=Department of Neurology, Massachusetts General Hospital kn-affil= affil-num=4 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=5 en-affil=Department of Pharmacy, Tokushima University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=7 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hospital Pharmacy and Pharmacology, Asahikawa Medical University and University Hospital kn-affil= affil-num=9 en-affil=Department of Medical Molecular Informatics, Meiji Pharmaceutical University kn-affil= affil-num=10 en-affil=Department of Pharmacy, Tokushima University Hospital kn-affil= en-keyword=Bile acids kn-keyword=Bile acids en-keyword=Multiple sclerosis kn-keyword=Multiple sclerosis en-keyword=Database analysis kn-keyword=Database analysis en-keyword=Drug repositioning kn-keyword=Drug repositioning en-keyword=Experimental autoimmune encephalomyelitis kn-keyword=Experimental autoimmune encephalomyelitis 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=21 cd-vols= no-issue= article-no= start-page=2247 end-page=2258 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=Surface Plasmon Resonances in Silver Nanodendrites : Trunk Length and Branch Connectivity Dependence en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study systematically investigates how trunk length and branch connectivity govern surface plasmon resonances in silver nanodendrites in the infrared (IR) region using a computational modeling strategy. We show that a continuous conductive trunk is essential for exciting long-wavelength collective plasmon modes. In a simulated bottom-up construction scheme, the trunk length is gradually increased to conductively connect additional branches to the backbone. Our results reveal that the fundamental δ mode resonance can be deterministically tuned across the mid-infrared spectrum (from 3840 nm to 4360 nm) primarily by controlling the trunk connectivity. As the number of connected branches grows, the lowest-order collective resonance peak exhibits a systematic redshift, and its resonance wavelength scales linearly with the effective dipole length Leff of the electron oscillation path. Concurrently, new higher-order modes emerge as local resonances of the connected substructures. These observations indicate that interrupting the conductive pathway causes a global collective mode to decompose into multiple resonances associated with more weakly coupled subsystems. The established linear scaling relationship provides a highly predictable design rule for this “programmable” connectivity, offering a robust platform for advanced applications such as multi-spectral infrared imaging, selective chemical sensing, and surface-enhanced infrared absorption (SEIRA) spectroscopy, where precise, a priori control over narrow-band infrared resonances is essential. en-copyright= kn-copyright= en-aut-name=MaQingyuan en-aut-sei=Ma en-aut-mei=Qingyuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KishidaYuki en-aut-sei=Kishida en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakeyasuNobuyuki en-aut-sei=Takeyasu en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShojiSatoru en-aut-sei=Shoji en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Informatics and Engineering, The University of Electro-communications kn-affil= affil-num=2 en-affil=Graduate School of Informatics and Engineering, The University of Electro-communications kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Informatics and Engineering, The University of Electro-communications kn-affil= en-keyword=Silver nanodendrites kn-keyword=Silver nanodendrites en-keyword=Surface plasmon resonances kn-keyword=Surface plasmon resonances en-keyword=Conductive coupling kn-keyword=Conductive coupling en-keyword=Topological connectivity kn-keyword=Topological connectivity en-keyword=Infrared nanoantennas kn-keyword=Infrared nanoantennas en-keyword=Plasmonic metamaterials kn-keyword=Plasmonic metamaterials END start-ver=1.4 cd-journal=joma no-vol=209 cd-vols= no-issue= article-no= start-page=117914 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=PPy-coated wire actuators for micromechanostimulation of cells ? identification of immediate-early responsive mechanoregulatory genes in osteoblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mechanotransduction, i.e., the conversion of mechanical cues into biochemical signals, is essential for bone development, remodeling, and adaptation. Although mechanical loading is known to regulate osteoblast function and bone homeostasis, dissecting the early and sustained mechanotransductive responses at the microscale remains challenging due to limitations of existing in vitro models. Here, we report the development and application of a mechanostimulation system comprising a polypyrrole (PPy)-based wire actuator that expands and contracts (4 μm in radius) upon electrical actuation and enables precise, localized micromechanical stimulation of a small number of cells within standard culture formats. Using this system, we applied short-term (30 min) cyclic (Cyc30) or static (Stat30), as well as prolonged (120 min) cyclic (Cyc120) stimulations to two osteoblast-like cells (MC3T3-E1 or KUSA-A1). Subsequent transcriptomic profiling and computational network analyses revealed that Cyc30 was not capable of inducing significant changes in mRNA expression, suggesting cellular adaptation to short-term cyclic loading. In contrast, Stat30 induced the upregulation of Fos, Btg2, Egr1, and Fosl1, all known genes associated with mechanotransduction, supporting the validity and reproducibility of our experimental mechanostimulation system. Notably, two long non-coding RNAs (B930036N10Rik and 5430431A17Rik) were identified for the first time as being upregulated in response to Stat30 stimuli. Among the differentially expressed genes (DEGs) upregulated by Cyc120 stimuli, Hmox1, a stress-inducible enzyme known for its roles in maintaining cellular homeostasis and promoting survival, was the only DEG repeatedly observed across the Cyc30/Cyc120 and Stat30/Cyc120 comparisons in both cell types, potentially emerging as a key stress-response gene under prolonged mechanical loading. Collectively, these results establish the PPy-based microactuator as a powerful tool for microscale mechanobiology, and provide molecular insight into immediate-early responsive transcriptional programs underlying osteoblastic mechanoadaptation conserved across different cell types. en-copyright= kn-copyright= en-aut-name=ChenJiamin en-aut-sei=Chen en-aut-mei=Jiamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Ortega-SantosAmaia B. en-aut-sei=Ortega-Santos en-aut-mei=Amaia B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HayanoSatoru en-aut-sei=Hayano en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=MartinezJose G. en-aut-sei=Martinez en-aut-mei=Jose G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaraEmilio Satoshi en-aut-sei=Hara en-aut-mei=Emilio Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=JagerEdwin W.H. en-aut-sei=Jager en-aut-mei=Edwin W.H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Physics, Chemistry and Biology (IFM), Link?ping University kn-affil= affil-num=3 en-affil=Department of Orthodontics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Physics, Chemistry and Biology (IFM), Link?ping University kn-affil= affil-num=6 en-affil=Department of Advanced International and Information Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Physics, Chemistry and Biology (IFM), Link?ping University kn-affil= affil-num=8 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Mechanotransduction kn-keyword=Mechanotransduction en-keyword=Mechanostimulation kn-keyword=Mechanostimulation en-keyword=Osteoblasts kn-keyword=Osteoblasts en-keyword=Polypyrrole kn-keyword=Polypyrrole END start-ver=1.4 cd-journal=joma no-vol=687 cd-vols= no-issue= article-no= start-page=120087 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=Phase diagram of Fe-C-S ternary system under planetary core conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=High-pressure, high-temperature experiments were conducted to investigate melting relations and phase assemblages in the Fe-C-S ternary system at 5 and 15 GPa, covering a temperature range of 1300?1900 K, conditions directly relevant to the Moon’s and Mercury’s cores. At 1300 K, the system is primarily governed by Fe-S eutectic melting, exhibiting notable complexity in the carbon-rich and sulfur-poor regions. With increasing temperature, the phase diagram simplifies: at 5 GPa and 1700 K, the Fe-Fe?C-FeS system features three regions (Fe+L, C + L, and L). Similar phase assemblages are observed at 15 GPa, with Fe7C3 and diamond replacing Fe3C and graphite, respectively. Extensive Fe+L, C + L, and L regions are observed at 1900 K.
For a Moon’s core composed of a Fe-C-S alloy, nearly pure Fe is the only viable inner core phase above 1700 K. Below this temperature, both Fe and Fe?C are potential solid inner core phases, depending on carbon content; a two-phase solid inner core is also theoretically possible. The inferred compositions of the outer core suggest densities of 6200?7300 kg/m?, with tighter constraints for models featuring an Fe?C core.
At Mercury-relevant pressures, either Fe or Fe?C? may form the solid inner core, again depending on carbon content. If the inner core is nearly pure Fe, the liquid outer core density ranges from 7300 to 7900 kg/m?. In both scenarios, a “snow” regime is plausible, though with distinct settling times. The ternary phase diagram indicates that Mercury is likely to develop a structurally layered inner core during secular cooling.
en-copyright= kn-copyright= en-aut-name=ZhaoBin en-aut-sei=Zhao en-aut-mei=Bin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZhuJintao en-aut-sei=Zhu en-aut-mei=Jintao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AntonangeliDaniele en-aut-sei=Antonangeli en-aut-mei=Daniele kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=ChenQi en-aut-sei=Chen en-aut-mei=Qi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=Mus?um National d’Histoire Naturelle, Sorbonne Universit?, UMR CNRS 7590, Institut de Min?ralogie, de Physique des Mat?riaux et de Cosmochimie, IMPMC kn-affil= affil-num=4 en-affil=Mus?um National d’Histoire Naturelle, Sorbonne Universit?, UMR CNRS 7590, Institut de Min?ralogie, de Physique des Mat?riaux et de Cosmochimie, IMPMC kn-affil= affil-num=5 en-affil=Center for Advanced Radiation Sources, University of Chicago kn-affil= affil-num=6 en-affil=Institute for Planetary Materials, Okayama University kn-affil= en-keyword=planetary core kn-keyword=planetary core en-keyword=phase diagram kn-keyword=phase diagram en-keyword=multi-anvil experiments kn-keyword=multi-anvil experiments en-keyword=iron alloy kn-keyword=iron alloy END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=14 article-no= start-page=6176 end-page=6185 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=Reversible Droplet Bridging and Tunable Viscoelasticity in Emulsions Using Biocompatible PLA-b-PEO-b-PLA Telechelic Block Copolymers: Implications for Injectable Emulsion Gels en-subtitle= kn-subtitle= en-abstract= kn-abstract=Telechelic polymers are known to form reversible networks through end-group association; however, their application as structuring agents in emulsion-based soft materials remains underexplored. Herein, we systematically investigate the biocompatible amphiphilic triblock copolymer poly(d,l-lactic acid)-block-poly(ethylene oxide)-block-poly(d,l-lactic acid)(PLA-b-PEO-b-PLA) as a rheology modifier in toluene-in-water model emulsions. Owing to the selective adsorption of PLA end blocks at the oil?water interface and the solvation of the PEO midblock in the aqueous phase, this polymer is expected to form reversible droplet-bridging networks. During the process, the polymer concentration, molecular weight of the mid and end blocks, and the dispersed phase volume fraction were adjusted, and the factors governing network formation were elucidated using oscillatory rheology and stress-relaxation measurements. The results show that anchoring of the PLA end blocks and PEO-mediated bridging predominantly control the strength and dynamic reversibility of the network. Step-strain experiments further reveal that the droplet-bridging interactions can be disrupted under large deformation and partially recover when small-strain conditions are restored, confirming the presence of reversible physical associations. These findings establish a molecular design strategy for biodegradable telechelic copolymers as effective and reprocessable structuring agents in emulsion gels. The shear-responsive, tunable, and reversible nature of the droplet-bridging network makes this material platform particularly suitable for injectable emulsion gels for advanced soft matter and biomedical engineering applications. en-copyright= kn-copyright= en-aut-name=NakayamaHinako en-aut-sei=Nakayama en-aut-mei=Hinako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoAtsushi en-aut-sei=Matsumoto en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IidaYuya en-aut-sei=Iida en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OnoTsutomu en-aut-sei=Ono en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= affil-num=1 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, University of Fukui kn-affil= affil-num=3 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=5 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= en-keyword=PLA-b-PEO-b-PLA kn-keyword=PLA-b-PEO-b-PLA en-keyword=telechelic polymer kn-keyword=telechelic polymer en-keyword=rheology kn-keyword=rheology en-keyword=emulsion gel kn-keyword=emulsion gel en-keyword=viscoelasticity kn-keyword=viscoelasticity END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=5 article-no= start-page=e2026GC012945 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=Chemical Geodynamics of Granitoid Magmatism During a Pacific‐Philippine Sea Plate Transition in Southwest Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Granitoid magmatism along the western Pacific margin records interactions between subduction dynamics and crust?mantle processes; however, the links between plate reorganization and magma-source evolution remain debated. Here we integrate U?Pb zircon geochronology with Pb?Sr?Nd?Hf isotope systematics to investigate Cretaceous?Paleogene granitoids in Southwest Japan. Zircon U?Pb ages define two discrete magmatic episodes at 110?60 Ma and 45?30 Ma, separated by a magmatic hiatus of ?10?15 Myr. These granitoid groups exhibit distinct isotopic signatures, indicating derivation from isotopically distinct magma sources linked to the paleo-Pacific (Izanagi) plate and the Philippine Sea plate, respectively. Isotope-based mass-balance modeling indicates higher sediment contributions to the older granitoids, with decreasing sediment input both landward and through time. The magmatic lull at ca. 52?40 Ma coincides with an abrupt isotopic shift and is interpreted to reflect plate reorganization, during which subduction of the paleo-Pacific plate was replaced by a transform or highly oblique plate boundary associated with the northward migration of the proto?Philippine Sea plate. Independent constraints from convergence rates, sediment flux, and accretionary complex development support this interpretation. These results demonstrate that granitoid magmatism in Southwest Japan was fundamentally controlled by temporal changes in subducted lithosphere and sediment flux driven by plate reorganization, highlighting the sensitivity of arc magmatism to transient tectonic regimes. en-copyright= kn-copyright= en-aut-name=DaoNghiem V. en-aut-sei=Dao en-aut-mei=Nghiem V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YemerTsegereda A. en-aut-sei=Yemer en-aut-mei=Tsegereda A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MwaisubaTulibako T. en-aut-sei=Mwaisuba en-aut-mei=Tulibako T. 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=KobayashiKatsura en-aut-sei=Kobayashi en-aut-mei=Katsura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ImaokaTeruyoshi en-aut-sei=Imaoka en-aut-mei=Teruyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University at Misasa kn-affil= affil-num=2 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University at Misasa kn-affil= affil-num=3 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University at Misasa kn-affil= affil-num=4 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University at Misasa kn-affil= affil-num=5 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University at Misasa kn-affil= affil-num=6 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University at Misasa kn-affil= affil-num=7 en-affil=Division of Earth Science, Graduate School of Sciences and Technology for Innovation, Yamaguchi University kn-affil= affil-num=8 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University at Misasa kn-affil= en-keyword=granitoids kn-keyword=granitoids en-keyword=Pb?Sr?Nd?Hf isotopes kn-keyword=Pb?Sr?Nd?Hf isotopes en-keyword=Pacific-Philippine Sea plates kn-keyword=Pacific-Philippine Sea plates en-keyword=sub-crustal origin kn-keyword=sub-crustal origin en-keyword=tectonic transition kn-keyword=tectonic transition END start-ver=1.4 cd-journal=joma no-vol=131 cd-vols= no-issue= article-no= start-page=e2025JE009453 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lateral Variations in Lunar Crustal Thickness Inferred From Apollo Seismic and GRAIL Gravity Data en-subtitle= kn-subtitle= en-abstract= kn-abstract=The internal structure of the Moon is key to understanding its formation, evolution, and bulk composition. In particular, determining the structure of the crust?mantle interface (Moho), including its lateral variations, is of significant importance, but current knowledge is still insufficient to fully constrain it. To address this, we used seismic wave arrivals from impact events, which yield constraints on the crust at both the impact sites and the Apollo stations, to invert for local crustal thickness. Based on a series of assumed crust and mantle density models, we compared Moho depths inferred from global gravity recovery and interior laboratory gravity data with those from seismic observations. Although the gravity‐derived results broadly capture the overall Moho relief, local discrepancies remain, with differences reaching up to 10 km in the vicinity of the Apollo 17 Saturn IVB impact site. These results may reflect regional geological anomalies and highlight the importance of incorporating multiple seismically constrained crustal thickness estimates as anchors in gravity inversions. Using seven seismic anchor points and assuming an upper mantle velocity of Vp = 7.68 km/ s, an upper mantle density of 3,280 kg/m3, and a crustal density of 2,693 kg/m3, we obtain an average lunar crustal thickness of 43.6 ± 1.9 km. The findings also provide valuable guidance for future global 3D modeling of the Moon. en-copyright= kn-copyright= en-aut-name=ZhangXiang en-aut-sei=Zhang en-aut-mei=Xiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawamuraTaichi en-aut-sei=Kawamura en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DrilleauM?lanie en-aut-sei=Drilleau en-aut-mei=M?lanie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Lognonn?Philippe en-aut-sei=Lognonn? en-aut-mei=Philippe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HenriSamuel en-aut-sei=Henri en-aut-mei=Samuel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=XuZongbo en-aut-sei=Xu en-aut-mei=Zongbo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OnoderaKeisuke en-aut-sei=Onodera en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BodinThomas en-aut-sei=Bodin en-aut-mei=Thomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Universit? Paris Cit?, Institut de physique du globe de Paris, CNRS kn-affil= affil-num=2 en-affil=Universit? Paris Cit?, Institut de physique du globe de Paris, CNRS kn-affil= affil-num=3 en-affil=Universit? Paris Cit?, Institut de physique du globe de Paris, CNRS kn-affil= affil-num=4 en-affil=Universit? Paris Cit?, Institut de physique du globe de Paris, CNRS kn-affil= affil-num=5 en-affil=Universit? Paris Cit?, Institut de physique du globe de Paris, CNRS kn-affil= affil-num=6 en-affil=Universit? Paris Cit?, Institut de physique du globe de Paris, CNRS kn-affil= affil-num=7 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=8 en-affil=Instituto de Ciencias del Mar (ICM)?CSIC kn-affil= END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue=2 article-no= start-page=170 end-page=181 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of Linear Interpolation System for SMK Model Parameters Evaluated from Cellular-Scale Simulation (LISMEC) and its application to BNCT dosimetry en-subtitle= kn-subtitle= en-abstract= kn-abstract=Boron neutron capture therapy (BNCT) utilizes high linear energy transfer (LET) α-particles and 7Li ions generated through the 10B(n, α)7Li reaction. Precise dosimetry is essential for maximizing therapeutic efficacy while minimizing normal tissue adverse events, considering the microscopic distribution of 10B and cellular structures. Recently, the photon isoeffective dose (DisoE) has been proposed as a more appropriate metric for BNCT treatment planning and can be evaluated using the stochastic microdosimetric kinetic (SMK) model. However, clinical implementation of the SMK model remains challenging due to the difficulty of evaluating its input parameters, which requires computationally intensive radiation transport simulations at the cellular scale. To address this issue, we developed LISMEC (Linear Interpolation System for Stochastic Microdosimetric Kinetic model parameters Evaluated from Cellular-scale simulation), a rapid estimation framework based on precomputed cellular-scale PHITS (Particle and Heavy Ion Transport code System) simulations covering various cell geometries and boron distributions. By applying a linear interpolation algorithm, LISMEC enables the retrieval of SMK model parameters without the need for computationally intensive cellular-scale simulations. The utility of LISMEC, in conjunction with PHITS, was demonstrated through simulations of various irradiation scenarios in reactor-based BNCT. The results showed that DisoE values ranged from 7.4 to 32.7 Gy, even under a fixed macroscopic 10B concentration of 60 ppm. These findings emphasize the importance of incorporating a microscopic distribution of 10B and cellular structures into BNCT treatment planning. en-copyright= kn-copyright= en-aut-name=ShigehiraTakafumi en-aut-sei=Shigehira en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeTubasa en-aut-sei=Watanabe en-aut-mei=Tubasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuzukiMinoru en-aut-sei=Suzuki en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirataYuho en-aut-sei=Hirata en-aut-mei=Yuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OgawaTatsuhiko en-aut-sei=Ogawa en-aut-mei=Tatsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=SakuraiYoshinori en-aut-sei=Sakurai en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatoTatsuhiko en-aut-sei=Sato en-aut-mei=Tatsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=2 en-affil=Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=3 en-affil=Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=4 en-affil=Research Group for Radiation Transport Analysis, Nuclear Science and Engineering Center , Japan Atomic Energy Agency (JAEA) kn-affil= affil-num=5 en-affil=Research Group for Radiation Transport Analysis, Nuclear Science and Engineering Center , Japan Atomic Energy Agency (JAEA) kn-affil= affil-num=6 en-affil=Department of Cellular Physiology, Neutron Therapy Research Center, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=8 en-affil=Research Group for Radiation Transport Analysis, Nuclear Science and Engineering Center , Japan Atomic Energy Agency (JAEA) kn-affil= en-keyword=BNCT kn-keyword=BNCT en-keyword=microdosimetry kn-keyword=microdosimetry en-keyword=borondistribution kn-keyword=borondistribution en-keyword=cellmorphology kn-keyword=cellmorphology END start-ver=1.4 cd-journal=joma no-vol=306 cd-vols= no-issue= article-no= start-page=129728 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=Instrument-free quantitative colorimetric analysis using adsorption-band length in a packed silica gel column en-subtitle= kn-subtitle= en-abstract= kn-abstract=A simple and instrument-free colorimetric method for quantitative analysis is reported, in which analyte concentration is determined by measuring the length of a colored adsorption band formed in a packed silica gel column. The proposed method employs a miniature silica gel column that acts as a signal transducer after it adsorbs the colored compound from a solution during its flow in the column. The length of this band increases proportionally with analyte concentration, which enables quantitative detection via simple distance measurement. A theoretical model was developed to describe the relationship between solute concentration, adsorption behavior, and band propagation along the column. The principle was validated via the detection of both iron ions and enzyme-mediated glutamic acid. For Fe2+ analysis, the o-phenanthroline complexation method shows a level of sensitivity comparable to that of conventional spectrophotometry, which enables an almost quantitative recovery of trace iron in tap water. The limit of detection (LOD) and the limit of quantification (LOQ) were estimated to be 0.20 μM and 0.60 μM for the proposed method and 0.23 μM and 0.70 μM for spectrophotometry, respectively. The approach was further extended to glutamate detection using a cascade reaction involving glutamate oxidase and horseradish peroxidase with N-benzoyl leucomethylene blue as the chromogenic substrate. The LOD and the LOQ of the proposed method were 0.08 and 0.25 μM, and both values are superior to the 0.24 μM and 0.73 μM obtained using a microplate reader. By integrating preconcentration with a distance-based readout, this method provides a simple yet highly sensitive analytical platform and establishes distance as a quantitative signal for colorimetric detection. en-copyright= kn-copyright= en-aut-name=PhonxayxiongSychanh en-aut-sei=Phonxayxiong en-aut-mei=Sychanh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanetaTakashi en-aut-sei=Kaneta en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil=Department of Chemistry, Okayama University kn-affil= en-keyword=Colorimetry kn-keyword=Colorimetry en-keyword=Distance-based detection kn-keyword=Distance-based detection en-keyword=Silica gel kn-keyword=Silica gel en-keyword=Adsorption kn-keyword=Adsorption END start-ver=1.4 cd-journal=joma no-vol=134 cd-vols= no-issue=4 article-no= start-page=225 end-page=231 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cation distribution and diffusion-path topologies of A-site-deficient perovskite LixLa(1?x)/3NbO3 en-subtitle= kn-subtitle= en-abstract= kn-abstract=LixLa(1?x)/3NbO3 with an A-site-deficient perovskite structure was investigated with a focus on the relationship between its atomic configuration and Li+ diffusion properties. To this end, total scattering (diffraction) measurements were performed, and then reverse Monte Carlo modeling using the data was employed to construct the atomic configuration. The results suggest that the partial occupancy of La in the La-poor layer facilitate Li+ diffusion across the layer owing to the volume contraction. Furthermore, topological analyses conducted via persistent homology using the constructed atomic configuration indicate that a large fourfold ring formed by Nb and O is one of the reasons for superior Li+ diffusion in LixLa(1?x)/3NbO3. en-copyright= kn-copyright= en-aut-name=KitamuraNaoto en-aut-sei=Kitamura en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TangYizhong en-aut-sei=Tang en-aut-mei=Yizhong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraKoji en-aut-sei=Kimura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ObayashiIppei en-aut-sei=Obayashi en-aut-mei=Ippei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OnoderaYohei en-aut-sei=Onodera en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakashimaKen en-aut-sei=Nakashima en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshibashiChiaki en-aut-sei=Ishibashi en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IdemotoYasushi en-aut-sei=Idemoto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HayashiKoichi en-aut-sei=Hayashi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science kn-affil= affil-num=2 en-affil=Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science kn-affil= affil-num=3 en-affil=Department of Physical Science and Engineering, Nagoya Institute of Technology kn-affil= affil-num=4 en-affil=Center for Artificial Intelligence and Mathematical Data Science, Okayama University kn-affil= affil-num=5 en-affil=Center for Basic Research on Materials, National Institute for Materials Science kn-affil= affil-num=6 en-affil=Faculty of Materials for Energy, Shimane University kn-affil= affil-num=7 en-affil=Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science kn-affil= affil-num=8 en-affil=Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science kn-affil= affil-num=9 en-affil=Department of Physical Science and Engineering, Nagoya Institute of Technology kn-affil= en-keyword=A-site-deficient perovskite kn-keyword=A-site-deficient perovskite en-keyword=Li+ conduction kn-keyword=Li+ conduction en-keyword=Total scattering kn-keyword=Total scattering en-keyword=Local structure kn-keyword=Local structure en-keyword=Persistent homology kn-keyword=Persistent homology END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=12889 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Explainable analysis of the complex maze magnetic domain structure through extension of the Landau free energy model by adding an entropy feature en-subtitle= kn-subtitle= en-abstract= kn-abstract=Maze magnetic domains exhibit complex, temperature-dependent behavior that impacts energy loss in soft magnets, yet their magnetization reversal mechanisms remain poorly understood due to current model limitations. To address this gap, we develop an entropy-extended Landau free energy model that incorporates thermal effects into the analysis of magnetic domain. We employ a data-driven pipeline combining persistent homology, energy decomposition, and principal component analysis to construct an interpretable model that quantifies structure?property relationships and enables causal analysis of magnetic pattern formation. Using this approach, we trace entropy increases to their origins in initial domain configurations and quantify energy transfer among entropic, demagnetization, and exchange contributions. We also find that domain wall lengthening tracks increasing structural complexity, yielding previously inaccessible insights into magnetization reversal mechanism and enabling automated visualization. Our entropy-augmented model provides an explainable framework to decipher magnetization processes and guide the design of magnetic materials to reduce energy loss. en-copyright= kn-copyright= en-aut-name=MasuzawaK. en-aut-sei=Masuzawa en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FoggiattoA. L. en-aut-sei=Foggiatto en-aut-mei=A. L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuniiS. en-aut-sei=Kunii en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagaokaR. en-aut-sei=Nagaoka en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaniwakiM. en-aut-sei=Taniwaki en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=MitsumataC. en-aut-sei=Mitsumata en-aut-mei=C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ObayashiI. en-aut-sei=Obayashi en-aut-mei=I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiraokaY. en-aut-sei=Hiraoka en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KotsugiM. en-aut-sei=Kotsugi en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Material Science and Technology, Tokyo University of Science kn-affil= affil-num=2 en-affil=Department of Material Science and Technology, Tokyo University of Science kn-affil= affil-num=3 en-affil=Department of Material Science and Technology, Tokyo University of Science kn-affil= affil-num=4 en-affil=Department of Material Science and Technology, Tokyo University of Science kn-affil= affil-num=5 en-affil=Department of Material Science and Technology, Tokyo University of Science kn-affil= affil-num=6 en-affil=Department of Material Science and Technology, Tokyo University of Science kn-affil= affil-num=7 en-affil=Department of Material Science and Technology, Tokyo University of Science kn-affil= affil-num=8 en-affil=Interdisciplinary Education and Research Field, Okayama University kn-affil= affil-num=9 en-affil=Kyoto University Institute for Advanced Study, Kyoto University kn-affil= affil-num=10 en-affil=Department of Material Science and Technology, Tokyo University of Science kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=5 article-no= start-page=e00824-24 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250527 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sodium butyrate inhibits the expression of virulence factors in Vibrio cholerae by targeting ToxT protein en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cholera, a diarrheal disease caused by the gram-negative bacterium Vibrio cholerae, remains a global health threat in developing countries due to its high transmissibility and increased antibiotic resistance. There is a pressing need for alternative strategies, with an emphasis on anti-virulent approaches to alter the outcome of bacterial infections, given the increase in antimicrobial-resistant strains. V. cholerae causes cholera by secreting virulence factors in the intestinal epithelial cells. These virulence factors facilitate bacterial colonization and cholera toxin production during infection. Here, we demonstrate that sodium butyrate (SB), a small molecule, had no effect on bacterial viability but was effective in suppressing the virulence attributes of V. cholerae. The production of cholera toxin (CT) was significantly reduced in a standard V. cholerae El Tor strain and two clinical isolates when grown in the presence of SB. Analysis of mRNA and protein levels further revealed that SB reduced the expression of the ToxT-dependent virulence genes like tcpA and ctxAB. DNA-protein interaction assays, conducted at cellular (ChIP) and in vitro conditions (EMSA), indicated that SB weakens the binding between ToxT and its downstream promoter DNA, likely by blocking DNA binding. Furthermore, the anti-virulence efficacy of SB was confirmed in animal models. These findings suggest that SB could be developed as an anti-virulence agent against V. cholerae, serving as a potential alternative to conventional antibiotics or as an adjunctive therapy to combat cholera. en-copyright= kn-copyright= en-aut-name=KunduSushmita en-aut-sei=Kundu en-aut-mei=Sushmita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DasSuman en-aut-sei=Das en-aut-mei=Suman kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaitraPriyanka en-aut-sei=Maitra en-aut-mei=Priyanka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HalderProlay en-aut-sei=Halder en-aut-mei=Prolay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KoleyHemanta en-aut-sei=Koley en-aut-mei=Hemanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MukhopadhyayAsish K. en-aut-sei=Mukhopadhyay en-aut-mei=Asish K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=DuttaShanta en-aut-sei=Dutta en-aut-mei=Shanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ChatterjeeNabendu Sekhar en-aut-sei=Chatterjee en-aut-mei=Nabendu Sekhar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=BhattacharyaSushmita en-aut-sei=Bhattacharya en-aut-mei=Sushmita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= affil-num=2 en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= affil-num=3 en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= affil-num=4 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= affil-num=5 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= affil-num=6 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= affil-num=7 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= affil-num=9 en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= affil-num=10 en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases) kn-affil= en-keyword=sodium butyrate (SB) kn-keyword=sodium butyrate (SB) en-keyword=inhibitor kn-keyword=inhibitor en-keyword=pathogenesis kn-keyword=pathogenesis en-keyword=Vibrio cholerae kn-keyword=Vibrio cholerae en-keyword=ctxAB kn-keyword=ctxAB en-keyword=antimicrobial resistance kn-keyword=antimicrobial resistance en-keyword=toxin-coregulated pilus (TcpA) kn-keyword=toxin-coregulated pilus (TcpA) END start-ver=1.4 cd-journal=joma no-vol=145 cd-vols= no-issue= article-no= start-page=108229 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=Real-world evaluation of Armstrong's criteria in corticobasal degeneration: Phenotypic overlap and diagnostic challenges en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Corticobasal degeneration (CBD) is a four-repeat tauopathy with heterogeneous clinical manifestations. Armstrong's criteria involve a two-step diagnostic approach: first, classifying patients into five clinical phenotypes?probable/possible corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), non-fluent/agrammatic variant primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS); second, determining whether they meet the clinical research criteria for probable CBD (cr-CBD) or the clinical criteria for possible CBD (p-CBD), which are distinct from the initial CBS classifications.
Objective: To investigate how real-world patients with suspected CBD fulfill Armstrong's clinical phenotypes and diagnostic criteria, and to compare clinical and imaging features between the Alzheimer's disease (AD) group and the non-AD group defined by CSF amyloid biomarkers.
Methods: We retrospectively reviewed 137 patients undergoing differential diagnosis for CBS, frontotemporal dementia, primary progressive aphasia, or PSPS. Of these, 78 met the criteria for cr-CBD (n = 36) or p-CBD (n = 42). CSF was examined in 32 patients, and based on the CSF Aβ42/40 ratio, patients were classified into an AD-group (AD-CBS; n = 6) and a non-AD group (n = 26).
Results: Among patients classified as cr-CBD or p-CBD, 79% fulfilled two or more clinical phenotypes, with FBS and PSPS most commonly. Compared with the AD group, the non-AD group showed more parkinsonian features and frontal hypoperfusion on [123I]-IMP SPECT.
Conclusion: Armstrong's criteria captured a spectrum of overlapping clinical features. While helpful in clinical phenotyping, further validation with biomarkers is essential to distinguish CBD from AD and related disorders. Prospective studies with pathological confirmation are warranted. en-copyright= kn-copyright= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomuraEmi en-aut-sei=Nomura en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OsakadaYosuke en-aut-sei=Osakada en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YunokiTaijun en-aut-sei=Yunoki en-aut-mei=Taijun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakemotoMami en-aut-sei=Takemoto en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Corticobasal degeneration kn-keyword=Corticobasal degeneration en-keyword=CBD kn-keyword=CBD en-keyword=Corticobasal syndrome kn-keyword=Corticobasal syndrome en-keyword=CBS kn-keyword=CBS en-keyword=Armstrong's criteria kn-keyword=Armstrong's criteria END start-ver=1.4 cd-journal=joma no-vol=481 cd-vols= no-issue= article-no= start-page=125733 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The utility of Gold Coast criteria for amyotrophic lateral sclerosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease. Current diagnostic criteria, including the revised El Escorial (rEE) and Awaji (AW) criteria, have limitations in sensitivity. The Gold Coast (GC) criteria were proposed to simplify diagnosis and improve early detection, but their real-world performance remains unclear.
Methods: We retrospectively analyzed 260 patients suspected of ALS who were admitted to our department between 2013 and 2022. The GC, AW, and rEE criteria were applied to data from initial hospitalization. Final diagnoses were based on follow-up data, and sensitivity/specificity were compared using McNemar's test.
Results: The GC criteria showed equivalent sensitivity (91.6 %), but higher specificity (75.9 %) compared to all combined AW and rEE categories. GC sensitivity was significantly higher than that of AW/rEE definite/probable categories. False negatives of GC criteria were often due to insufficient LMN signs, particularly in bulbar-onset cases. Subgroup analysis showed consistent trends.
Conclusion: The GC criteria demonstrated high sensitivity and moderate specificity, supporting their clinical utility in early ALS diagnosis. However, variability in clinical presentation and retrospective limitations suggest the need for further prospective validation. en-copyright= kn-copyright= en-aut-name=NomuraEmi en-aut-sei=Nomura en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OsakadaYosuke en-aut-sei=Osakada en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YunokiTaijun en-aut-sei=Yunoki en-aut-mei=Taijun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakemotoMami en-aut-sei=Takemoto en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Amyotrophic lateral sclerosis kn-keyword=Amyotrophic lateral sclerosis en-keyword=ALS kn-keyword=ALS en-keyword=Gold Coast criteria kn-keyword=Gold Coast criteria en-keyword=Revised El Escorial criteria kn-keyword=Revised El Escorial criteria en-keyword=Awaji criteria kn-keyword=Awaji criteria END start-ver=1.4 cd-journal=joma no-vol=211 cd-vols= no-issue= article-no= start-page=104882 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=Lease or sale: When a durable goods monopolist can choose supply chain openness en-subtitle= kn-subtitle= en-abstract= kn-abstract=We construct a two-period model of supply chain openness in a durable goods market with two marketing modes: leasing and selling. For a given marketing mode, at the beginning of the first period, an incumbent supplier and the downstream monopolist choose one of two trading modes: (i) a two-period exclusive supply chain, or (ii) an open supply chain, allowing the downstream monopolist to trade with an efficient supplier in the second period. We show that in the selling mode, the exclusive supply chain can arise if the incumbent supplier is highly efficient. In contrast, under the leasing mode, the exclusive supply chain never arises; instead, the open supply chain is always selected. Furthermore, when the downstream monopolist is allowed to endogenously choose the marketing mode before the first period, it opts for the selling mode if the incumbent supplier is relatively inefficient; otherwise, it selects the leasing mode. Regardless of the chosen marketing mode, the open supply chain always arises on the equilibrium path, implying that the recent advancement of ICT to enhance leasing may discourage the adoption of exclusive supply chains. en-copyright= kn-copyright= en-aut-name=KitamuraHiroshi en-aut-sei=Kitamura en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsushimaNoriaki en-aut-sei=Matsushima en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoMisato en-aut-sei=Sato en-aut-mei=Misato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Faculty of Economics, Kyoto Sangyo University kn-affil= affil-num=2 en-affil=Osaka School of International Public Policy, University of Osaka kn-affil= affil-num=3 en-affil=Faculty of Humanities and Social Sciences, Okayama University kn-affil= en-keyword=Durable goods kn-keyword=Durable goods en-keyword=Exclusive supply chain kn-keyword=Exclusive supply chain en-keyword=Vertical relation kn-keyword=Vertical relation en-keyword=Selling versus leasing kn-keyword=Selling versus leasing 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=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=113 cd-vols= no-issue=4 article-no= start-page=043713 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260408 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Analytical and numerical studies of periodic superradiance en-subtitle= kn-subtitle= en-abstract= kn-abstract=We conduct a theoretical study to understand the periodic superradiance observed in an Er:YSO crystal. First, we construct a model based on the Maxwell-Bloch equations for a reduced level system, a pair of superradiance states, and a population reservoir state. Analysis of the eigenvalues of the linearized differential equations shows that periodic superradiance can be realized only for certain parameters. We also derive two-variable equations consisting of the coherence and population difference between the two superradiance states, which contain the essential feature of the periodic superradiance. The two-variable equations clarify the mathematical structure of this periodic phenomenon and give analytical forms of the period, pulse duration, and number of emitted photons. Our model successfully reproduces the periodic behavior, but the actual experimental parameters are found to be outside the parameter region for the periodic superradiance. This result implies that some other mechanism(s) is (are) required. As one example, assuming that the field decay rate varies with the electric field, the periodic superradiance can be reproduced even under the actual experimental conditions. en-copyright= kn-copyright= en-aut-name=HaraHideaki en-aut-sei=Hara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyamotoYuki en-aut-sei=Miyamoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HanJunseok en-aut-sei=Han en-aut-mei=Junseok kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OmotoRiku en-aut-sei=Omoto en-aut-mei=Riku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImaiYasutaka en-aut-sei=Imai en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshimiAkihiro en-aut-sei=Yoshimi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshimuraKoji en-aut-sei=Yoshimura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshimuraMotohiko en-aut-sei=Yoshimura en-aut-mei=Motohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SasaoNoboru en-aut-sei=Sasao en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=5 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=7 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=8 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=9 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=4 article-no= start-page=1769 end-page=1784 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=P53-armed Oncolytic Adenovirus Enhances the Efficacy of PD-1 Blockade in Neuroblastoma by Inducing Immunogenic Cell Death en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system. Although immunotherapy with immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) has emerged as novel antitumor therapy, high-risk NB tumors are refractory to ICI therapy. Oncolytic virotherapy is expected to potentiate the antitumor immune response by inducing immunogenic cell death (ICD). In the present study, we assessed the therapeutic potential of OBP-301 and OBP-702, telomerase-specific oncolytic adenoviruses, for the induction of ICD and combined effect with PD-1 blockade against NB cells.
Materials and Methods: The cytopathic activity of OBP-301 and OBP-702 was assessed using three human MYCN-amplified NB cell lines (IMR-32, LA-N-5, and NB-1) and a murine non-MYCN-amplified NB cell line (Neuro-2a). Virus-mediated antitumor effect was assessed by analyzing cell viability, secretion of extracellular adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1), apoptosis, autophagy, and PD-L1 levels. A subcutaneous Neuro-2a tumor model was used to evaluate the in vivo antitumor effect of combination therapy with OBP-702 and anti-PD-1 antibody.
Results: OBP-702 exhibited stronger cytopathic activity, inducing ICD with secretion of ATP and HMGB1, compared to OBP-301 in human and murine NB cells. OBP-301 and OBP-702 increased apoptosis, autophagy, and PD-L1 expression in murine NB cells. Moreover, OBP-702 significantly prolonged the survival of tumor-bearing mice compared to monotherapy with PD-1 blockade.
Conclusion: OBP-702 is a promising antitumor strategy to promote the antitumor effect of ICIs by inducing ICD against NB tumors. en-copyright= kn-copyright= en-aut-name=TANIMORIMICHI en-aut-sei=TANI en-aut-mei=MORIMICHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TAZAWAHIROSHI en-aut-sei=TAZAWA en-aut-mei=HIROSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TANIMOTOTERUTAKA en-aut-sei=TANIMOTO en-aut-mei=TERUTAKA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NOUSOHIROSHI en-aut-sei=NOUSO en-aut-mei=HIROSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WATANABEHINAKO en-aut-sei=WATANABE en-aut-mei=HINAKO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OYAMATAKANORI en-aut-sei=OYAMA en-aut-mei=TAKANORI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=URATAYASUO en-aut-sei=URATA en-aut-mei=YASUO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KAGAWASHUNSUKE en-aut-sei=KAGAWA en-aut-mei=SHUNSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NODATAKUO en-aut-sei=NODA en-aut-mei=TAKUO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KURODASHINJI en-aut-sei=KURODA en-aut-mei=SHINJI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FUJIWARATOSHIYOSHI en-aut-sei=FUJIWARA en-aut-mei=TOSHIYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Neuroblastoma kn-keyword=Neuroblastoma en-keyword=oncolytic adenovirus kn-keyword=oncolytic adenovirus en-keyword=p53 kn-keyword=p53 en-keyword=immunogenic cell death kn-keyword=immunogenic cell death en-keyword=PD-1 kn-keyword=PD-1 END