start-ver=1.4 cd-journal=joma no-vol=85 cd-vols= no-issue=9 article-no= start-page=2608 end-page=2618 dt-received= dt-revised= dt-accepted= dt-pub-year=2002 dt-pub=200209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A New Route for Preparation of 5-Deoxy-5-(hydroxyphosphinyl)- D-mannopyranose and -L-gulopyranose Derivatives en-subtitle= kn-subtitle= en-abstract= kn-abstract=Starting from methyl 2,3-O-isopropylidene-α-D-mannofuranoside (5), methyl 6-O-benzyl-2,3-O-isopropylidene-α-D-lyxo-hexofuranosid-5-ulose (12) was prepared in three steps. The addition reaction of dimethyl phosphonate to 12, followed by deoxygenation of 5-OH group, provided the 5-deoxy-5-dimethoxyphosphinyl-α-D-mannofuranoside derivative 15a and the β-L-gulofuranoside isomer 15b. Reduction of 15a and 15b with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by the action of HCl and then H2O2, afforded the D-mannopyranose (17) and L-gulopyranose analog 21, each having a phosphinyl group in the hemiacetal ring. These were converted to the corresponding 1,2,3,4,6-penta-O-acetyl-5-methoxyphosphinyl derivatives 19 and 23, respectively, structures and conformations (4C1 or 1C4, resp.) of which were established by 1H-NMR spectroscopy. en-copyright= kn-copyright= en-aut-name=HanayaTadashi en-aut-sei=Hanaya en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoHiroshi en-aut-sei=Yamamoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Center of Instrumental Analysis, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20261007 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Temporally structured plasticity in death-feigning behavior in response to nutritional conditions in Tribolium castaneum en-subtitle= kn-subtitle= en-abstract= kn-abstract=Investment in antipredator behavior and foraging both directly influence fitness, yet these investments are often subject to trade-offs. In income-breeding species, individuals may initially prioritize foraging after adult emergence and subsequently increase investment in antipredator behavior as their nutritional condition improves. In this study, we investigated temporal changes in death-feigning behavior, an antipredator response, in the red flour beetle Tribolium castaneum from immediately after adult emergence. Both fed and starved individuals exhibited an increase in death-feigning duration with time after emergence. However, in starved individuals, this trend reversed after approximately 15 days, with a marked decline in duration. These results suggest that the increase in investment in death-feigning behavior early in adulthood is relatively inflexible, whereas behavioral responses become highly plastic in response to environmental conditions around day 15. Furthermore, individuals that were fed until day 18 before starvation showed a less pronounced behavioral change than those subjected to starvation from the beginning of the experimental period, suggesting that the timing of environmental exposure may influence subsequent behavioral responses. Together, these findings suggest that behavioral plasticity is not constant over time but is instead structured across developmental stages. We propose a novel conceptual framework, termed temporally structured plasticity (TSP), to describe this pattern. en-copyright= kn-copyright= en-aut-name=ShibuyaKohjiro en-aut-sei=Shibuya en-aut-mei=Kohjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumuraKentarou en-aut-sei=Matsumura en-aut-mei=Kentarou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyatakeTakahisa en-aut-sei=Miyatake en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of General Systems Studies, Graduate School of Arts and Sciences, The University of Tokyo kn-affil= affil-num=3 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Avoiding attack kn-keyword=Avoiding attack en-keyword=Beetle kn-keyword=Beetle en-keyword=Playing dead kn-keyword=Playing dead en-keyword=Thanatosis kn-keyword=Thanatosis en-keyword=Post-contact immobility kn-keyword=Post-contact immobility en-keyword=Tonic immobility kn-keyword=Tonic immobility END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=3 article-no= start-page=1525 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bioinformatic Prediction of Activation States in Molecular Network Pathways of Eukaryotic Initiation Factor 2 (EIF2) Signaling and Coronavirus Pathogenesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Eukaryotic initiation factor 2 (EIF2) signaling plays a crucial role in regulating mRNA translation and initiating eukaryotic protein synthesis. Computational molecular network pathway analysis of the canonical pathways of the coronaviral infection revealed that EIF2 signaling is inactivated when the coronavirus pathogenesis pathway is activated and vice versa. Our computational analyses indicated that the coronavirus pathogenesis pathway and EIF2 signaling had inverse activation states. Computational investigation of upstream or downstream microRNA (miRNA) revealed that EIF2 signaling directly interacted with miRNAs, including let-7, miR-1292-3p (miRNAs with the seed CGCGCCC), miR-15, miR-34, miR-378, miR-493, miR-497, miR-7, miR-8, and MIRLET7. A total of 36 nodes, including 8 molecules (ATF4, BCL2, CCND1, DDIT3, EIF2A, EIF2AK3, EIF4E, and ERK1/2), 1 complex (the ribosomal 40s subunit), and 1 function (apoptosis) in the coronavirus pathogenesis pathway, overlapped with EIF2 signaling. Alterations in EIF2 signaling may play a role in the pathogenesis of coronavirus. en-copyright= kn-copyright= en-aut-name=TanabeShihori en-aut-sei=Tanabe en-aut-mei=Shihori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=QuaderSabina en-aut-sei=Quader en-aut-mei=Sabina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnoRyuichi en-aut-sei=Ono en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaHiroyoshi Y. en-aut-sei=Tanaka en-aut-mei=Hiroyoshi Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CabralHoracio en-aut-sei=Cabral en-aut-mei=Horacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=2 en-affil=Innovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion kn-affil= affil-num=3 en-affil=Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=4 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Bioengineering, Graduate School of Engineering, The University of Tokyo kn-affil= en-keyword=coronavirus kn-keyword=coronavirus en-keyword=EIF2 signaling kn-keyword=EIF2 signaling en-keyword=microRNA kn-keyword=microRNA en-keyword=molecular pathway kn-keyword=molecular pathway en-keyword=network activation kn-keyword=network activation END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20261005 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Experimental evolution of female mating responses to infertile males in Tribolium castaneum en-subtitle= kn-subtitle= en-abstract= kn-abstract=In many animal populations, infertile males—those unable to reproduce—are commonly present. If females mate exclusively with such males, they fail to produce offspring. How, then, do females deal with this situation? Distinguishing infertile from fertile males both before and after copulation is difficult for females. Here, we tested the hypothesis of bet-hedging polyandry, in which females mitigate the risk of reproductive failure by mating with multiple males, using experimental evolution in the red flour beetle (Tribolium castaneum). Females were cohabited with males artificially sterilized by sublethal radiation and with untreated males at a 1:1 ratio (sterile:untreated). After more than 15 generations, females from the treatment strains did not avoid mating with infertile males, leading to reduced reproductive success. However, compared with the control strains, females from the treated strains tended to mate with a greater number of males. The results raise the possibility that increased polyandry (mating with multiple males) may evolve rather than relying on pre- or post-copulatory discrimination to mitigate the risk posed by infertile males. Bet-hedging is a strategy that spreads or minimizes risk under uncertainty, and these results are consistent with the hypothesis that polyandry can function as a bet-hedging strategy against uncertain male fertility. en-copyright= kn-copyright= en-aut-name=FujiiYui en-aut-sei=Fujii en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsanoYui en-aut-sei=Asano en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KoriKenta en-aut-sei=Kori en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumuraKentarou en-aut-sei=Matsumura en-aut-mei=Kentarou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YasuiYukio en-aut-sei=Yasui en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HimuroChihiro en-aut-sei=Himuro en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamotoYutaka en-aut-sei=Nakamoto en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SokeiYoshitaka en-aut-sei=Sokei en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyatakeTakahisa en-aut-sei=Miyatake en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Faculty of Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Arts and Sciences, The University of Tokyo kn-affil= affil-num=5 en-affil=Faculty of Agriculture, Kagawa University kn-affil= affil-num=6 en-affil=Okinawa Prefectural Plant Protection Center kn-affil= affil-num=7 en-affil=Okinawa Prefectural Plant Protection Center kn-affil= affil-num=8 en-affil=Okinawa Prefectural Plant Protection Center kn-affil= affil-num=9 en-affil=Faculty of Environmental, Natural Science and Technology, Okayama University kn-affil= en-keyword=Beetle kn-keyword=Beetle en-keyword=Bet-hedging kn-keyword=Bet-hedging en-keyword=Copulation kn-keyword=Copulation en-keyword=Matingbehavior kn-keyword=Matingbehavior en-keyword=Reproductive failure kn-keyword=Reproductive failure END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=11 article-no= start-page=132 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20261007 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=No evidence for differential allocation or sex ratio adjustment in response to male attractiveness in the broad-horned flour beetle en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sexual selection theory predicts that females can enhance the benefits of mate choice by increasing reproductive investment (differential allocation) or by biasing offspring sex ratios toward sons (sex ratio adjustment) when mating with attractive males. Clear empirical support for these hypotheses has been documented in many vertebrate taxa, whereas relatively few studies have tested them in invertebrates. Here, we investigated whether females adjust reproductive investment and offspring sex ratio in response to male attractiveness in the beetle Gnatocerus cornutus. We assessed male attractiveness using copulation latency and examined its associations with female lifetime reproductive success, egg size, and offspring sex ratio under single-mating conditions. Our results, however, provide no support for either the differential allocation or sex ratio adjustment hypotheses: females did not alter reproductive investment or offspring sex ratio according to mate quality. In this species, male sexual phenotypes are strongly influenced by environmental conditions. Such phenotype–genotype mismatches may reduce the reliability of male traits as indicators of genetic quality and increase the likelihood of assessment errors by females. This may explain the absence of maternal allocation in relation to mate attractiveness in G. cornutus. Instead, previous work on this beetle indicates that females can secure genetic benefits by remating with more attractive males and biasing fertilization toward their sperm. Our findings therefore suggest that postcopulatory mechanisms, rather than differential maternal allocation, provide a more effective route for females to secure the benefits of mate choice in G. cornutus. en-copyright= kn-copyright= en-aut-name=OkadaKensuke en-aut-sei=Okada en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KiyoseKatsuya en-aut-sei=Kiyose en-aut-mei=Katsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatsukiMasako en-aut-sei=Katsuki en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Seibukasei Co., Ltd kn-affil= affil-num=3 en-affil=Graduate School of Bioagricultural Sciences, Nagoya University kn-affil= en-keyword=Fisherian process kn-keyword=Fisherian process en-keyword=good genes kn-keyword=good genes en-keyword=horned beetle kn-keyword=horned beetle en-keyword=life-history evolution kn-keyword=life-history evolution en-keyword=sexual selection kn-keyword=sexual selection END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=10 article-no= start-page=e70299 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Interstitial Lung Disease in Patients With Unresectable Stage III NSCLC Treated With Chemoradiotherapy Followed by Durvalumab in Japan: Analysis From the Multicenter Prospective AYAME Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Interstitial lung disease (ILD) is a concerning adverse event associated with immune checkpoint inhibitors, including durvalumab. This analysis of the multicenter AYAME study assessed the longterm safety of durvalumab, focusing on ILD.
Methods: AYAME enrolled patients prescribed durvalumab for unresectable stage III non-small cell lung cancer (NSCLC) after chemoradiotherapy (CRT) from July 2019 to December 2020 in Japan. Patients received durvalumab for ≤ 12 months and were prospectively followed for 3 years. Incidence, severity, and management of ILD were examined. Multivariable logistic regression analysis was conducted to investigate the association of patient characteristics with grade ≥ 2 ILD occurrence.
Results: Of 511 patients in the safety analysis population, ILD occurred in 383 patients (75.0%) from durvalumab initiation to subsequent treatment start; median time to occurrence was 44.0 days. ILD led to permanent durvalumab discontinuation in 121/383 patients (31.6%), dose interruption in 111/383 (29.0%), and corticosteroid intervention in 168/383 (43.9%). Grade ≥ 2 ILD occurrence was higher in patients with volume of lung parenchyma that received 20 Gy (V20) ≥ 25% versus < 25% (60.3% vs. 29.4%; adjusted odds ratio 2.20, 95% confidence interval 1.08–4.48), 5 Gy (V5) ≥ median (37.85%) versus < median (51.5% vs. 27.2%; 1.79, 1.07–3.00), and grade 1 ILD before durvalumab administration versus no ILD (50.0% vs. 37.6%; 2.11, 1.07–4.17).
Conclusions: This study of durvalumab for NSCLC after CRT in a real-world setting indicated factors associated with grade ≥ 2 ILD and provided valuable insights into ILD management strategies. These findings may contribute to establishing effective approaches to minimize ILD risk in practice.
Trial Registration: UMIN000037090/NCT03995875 en-copyright= kn-copyright= en-aut-name=YamamotoNobuyuki en-aut-sei=Yamamoto en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KenmotsuHirotsugu en-aut-sei=Kenmotsu en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkdemirBurak en-aut-sei=Akdemir en-aut-mei=Burak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UematsuShinya en-aut-sei=Uematsu en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuiAyako en-aut-sei=Fukui en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KotoRyo en-aut-sei=Koto en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiwaraMasakazu en-aut-sei=Fujiwara en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwaoChikako en-aut-sei=Iwao en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitagawaHiroshi en-aut-sei=Kitagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshinoIchiro en-aut-sei=Yoshino en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GemmaAkihiko en-aut-sei=Gemma en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MitsudomiTetsuya en-aut-sei=Mitsudomi en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SaitoYoshinobu en-aut-sei=Saito en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= affil-num=2 en-affil=Division of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Oncology Medical, AstraZeneca K.K kn-affil= affil-num=5 en-affil=Oncology Medical, AstraZeneca K.K kn-affil= affil-num=6 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K kn-affil= affil-num=7 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K kn-affil= affil-num=8 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K kn-affil= affil-num=9 en-affil=Oncology Medical, AstraZeneca K.K kn-affil= affil-num=10 en-affil=Oncology Medical, AstraZeneca K.K kn-affil= affil-num=11 en-affil=Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital kn-affil= affil-num=12 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=13 en-affil=Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Pulmonary Medicine, Nippon Medical School Musashi Kosugi Hospital kn-affil= en-keyword=carcinoma kn-keyword=carcinoma en-keyword=chemoradiotherapy kn-keyword=chemoradiotherapy en-keyword=durvalumab kn-keyword=durvalumab en-keyword=interstitial kn-keyword=interstitial en-keyword=lung diseases kn-keyword=lung diseases en-keyword=non-small- cell lung kn-keyword=non-small- cell lung END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=5 article-no= start-page=e84709 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250523 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phase II Study of Platinum Re-administration in Non-small Cell Lung Cancer Following Chemoimmunotherapy Resistance en-subtitle= kn-subtitle= en-abstract= kn-abstract=Platinum compounds represent standard treatments for various cancers. However, the efficacy of re-administrating platinum compounds has been demonstrated only in ovarian cancer and small cell lung cancer (SCLC), with its utility in non-small cell lung cancer (NSCLC) remaining unclear. Given that the prognosis of NSCLC has improved with effective treatments such as immune checkpoint inhibitors (ICIs), we propose a multicenter, single-arm, prospective phase II trial of re-administrating platinum-based combination therapy for NSCLC. Patients with NSCLC who have progressed after chemoimmunotherapy and exhibit a platinum-free interval of 85 days or more will receive carboplatin combination therapy. The drugs combined with carboplatin - pemetrexed, nab-paclitaxel, or gemcitabine - must not have been administered previously. The primary endpoint is progression-free survival (PFS), assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Assuming a threshold PFS of 4.2 months and an expected hazard ratio of 0.60, the required sample size is calculated as 40 patients to achieve 70% power with a 5% alpha error. Secondary endpoints included objective response rate, toxicity, and overall survival. This study will clarify the efficacy of re-administrating platinum compounds to patients with NSCLC who have developed resistance to chemoimmunotherapy. en-copyright= kn-copyright= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HosokawaShinobu en-aut-sei=Hosokawa en-aut-mei=Shinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokoyamaToshihide en-aut-sei=Yokoyama en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugimotoKeisuke en-aut-sei=Sugimoto en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KudoKenichiro en-aut-sei=Kudo en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkadaToshiaki en-aut-sei=Okada en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaedaTadashi en-aut-sei=Maeda en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawaiHaruyuki en-aut-sei=Kawai en-aut-mei=Haruyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasugiMasayuki en-aut-sei=Yasugi en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=InoueKoji en-aut-sei=Inoue en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NinomiyaTakashi en-aut-sei=Ninomiya en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OzeIsao en-aut-sei=Oze en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=3 en-affil=Respiratory Medicine, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=5 en-affil=Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= affil-num=6 en-affil=Respiratory Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=7 en-affil=Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=8 en-affil=Respiratory Medicine, National Hospital Organization Yamaguchi Ube Medical Center kn-affil= affil-num=9 en-affil=Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=10 en-affil=Respiratory Medicine, Chugoku Central Hospital kn-affil= affil-num=11 en-affil=Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=12 en-affil=Respiratory Medicine, Iwakuni Medical Center kn-affil= affil-num=13 en-affil=Respiratory Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=14 en-affil=Division of Molecular Medicine, Aichi Cancer Center Research Institute kn-affil= affil-num=15 en-affil=Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= en-keyword=carboplatin kn-keyword=carboplatin en-keyword=clinical trial kn-keyword=clinical trial en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=platinum-free interval kn-keyword=platinum-free interval en-keyword=re-administration kn-keyword=re-administration END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=2 article-no= start-page=e79601 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Elevated Plasma Progastrin-Releasing Peptide Levels Associated With the Diagnosis of Pulmonary Carcinoid Tumors: A Report of Two Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary carcinoids are the type of thoracic malignant tumors classified as neuroendocrine tumors. Case 1 involved a 59-year-old woman with a nodular shadow in the left upper pulmonary field observed on chest radiography. Chest computed tomography (CT) scan revealed a nodule in the left upper lobe and a soft tissue tumor near the left third rib. Given her elevated plasma progastrin-releasing peptide (ProGRP) level, a CT-guided biopsy was performed, confirming a diagnosis of pulmonary carcinoid with solitary bone metastasis. She subsequently underwent partial resection of the left upper lobe and the rib tumor. Case 2 involved a 67-year-old woman referred to our hospital after a chest CT scan revealed a nodule in the left lingular region. Her plasma ProGRP level was elevated, and a CT-guided biopsy confirmed a diagnosis of pulmonary carcinoid. As no lymph node metastases were detected, she underwent segmental resection of the left upper lobe. In both cases, plasma ProGRP levels decreased following surgical resection. These findings suggest that plasma ProGRP levels may serve as a useful diagnostic marker for pulmonary carcinoids. en-copyright= kn-copyright= en-aut-name=YamaokaTakashi en-aut-sei=Yamaoka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NoumiTaku en-aut-sei=Noumi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoChiaki en-aut-sei=Matsumoto en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugimotoKeisuke en-aut-sei=Sugimoto en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= en-keyword=biopsy kn-keyword=biopsy en-keyword=case report kn-keyword=case report en-keyword=progrp kn-keyword=progrp en-keyword=pulmonary carcinoid kn-keyword=pulmonary carcinoid en-keyword=tumor marker kn-keyword=tumor marker END start-ver=1.4 cd-journal=joma no-vol=234 cd-vols= no-issue= article-no= start-page=112260 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The eukaryotic host–microbe–phage–nutrition interplay determines the bacterial effectors of supplemental lysine’s health benefits: An experimental cellular senescence model of digestive conditions in older adults en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recently, the consumption of various forms of the nutritive amino acid lysine (e.g., nutraceuticals and dietary supplements) has increased, particularly among the elderly, as it cannot be synthesized by the human body and plays a crucial role in several cellular physiological processes, including intestinal calcium and iron absorption, proteinogenesis, and fatty acid metabolism. However, the biochemical and immunological events that occur within the eukaryotic host-microbe-phage-nutrition interaction, especially when high amounts of lysine are consumed in nutraceutical or dietary supplement form by the elderly due to age-related requirements, as well as the impact on gut bacteria-derived metabolites, have not yet been fully studied. We hypothesized that (1) within an infectious-inflamed digestive milieu, the metabolism of excess extracellular lysine differs between young and senescent digestive cells, and (2) phages within the milieu exhibit alterations in host-microbe cometabolite signal profiles. To address this, we examined how gut microbes and phages, key regulators of eukaryotic host physiology, influence the immunometabolism of excess lysine. By combining two models of young and senescent digestive cells, the pathogenic P. aeruginosa PAO1, the Pseudomonas phage KPP22, and the anti-inflammatory bacterium Intestinimonas butyriciproducens, and simulating the pathogenesis of the interactive process of excessive lysine ingestion, we developed a five-way screening approach to explore key cell readouts, including viability, integrity, and function of the epithelial barrier, as well as cellular immunometabolic responses to exogenous lysine supplementation in cultures under infectious inflammation. Our findings are consistent with the possibility that host–microbe–microbe interactions involving lysine utilization and cross-feeding may influence the effects of lysine supplementation. These effects, whether beneficial or detrimental, can depend on the bacterial community, including the presence of pathogenic or potentially beneficial bacteria, interactions with intestinal phages, and the physiological conditions and metabolic requirements of the host and individual microbial taxa. en-copyright= kn-copyright= en-aut-name=GhadimiDarab en-aut-sei=Ghadimi en-aut-mei=Darab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BlömerSophia en-aut-sei=Blömer en-aut-mei=Sophia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KAYAAysel ŞAHİN en-aut-sei=KAYA en-aut-mei=Aysel ŞAHİN kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KrügerSandra en-aut-sei=Krüger en-aut-mei=Sandra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RöckenChristoph en-aut-sei=Röcken en-aut-mei=Christoph kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SchäferHeiner en-aut-sei=Schäfer 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=212 cd-vols= no-issue=6 article-no= start-page=e70252 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=Validation and Fine Mapping of Quantitative Trait Loci Associated With Salinity Tolerance at Reproductive Stage on Chromosome 6 in the Rice Variety Nona Bokra en-subtitle= kn-subtitle= en-abstract= kn-abstract=Soil salinity is a major abiotic stress affecting rice production globally. Previously, one promising salinity-tolerant line (SL535) was identified through screening of Nona Bokra-CSSLs with a Koshihikari background. In 2016, 102 F2 individuals derived from SL535/Koshihikari were evaluated under long-term salt stress, with salt treatment imposed from the active tillering stage to maturity to investigate salt tolerance at the reproductive stage. Three QTLs for plant dry weight, panicle number, and panicle weight were detected on chromosome 6. This genomic region was further validated in 2019 and 2020 for plant dry weight, tiller number, and Na+ and Cl− contents using homozygous lines with or without the Nona Bokra allele in a Koshihikari background. As expected, significantly higher tiller number and lower Na+ and Cl− contents were maintained in plants carrying the Nona Bokra allele (NIL) at the full-heading stage. In 2023, seven newly developed NILs were evaluated for agronomic traits under control and salt stress conditions. Based on their performance, the QTL for plant dry weight, qPDW6.1, was narrowed down to a 390 kb region ranging from 4.78 to 5.17 Mb on chromosome 6. Within this region, several stress-related candidate genes were predicted based on annotation information and variant effect prediction analysis. Among them, two genes, Os06g0196700 (Auxin response factor 1) and Os06g0199100 (P-type pentatricopeptide repeat protein), were considered the most likely candidate genes associated with salt tolerance. These findings provide a foundation for future gene cloning and functional validation studies, which may help elucidate the genetic and molecular mechanisms underlying salt tolerance at the reproductive stage. en-copyright= kn-copyright= en-aut-name=Emam AhmedM M en-aut-sei=Emam Ahmed en-aut-mei=M M kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaeokaKoki en-aut-sei=Maeoka en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakataYuki en-aut-sei=Sakata en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomitaAsami en-aut-sei=Tomita en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HiraiYoshihiko en-aut-sei=Hirai en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= 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 Environment and Life Science, Okayama University kn-affil= affil-num=3 en-affil=School of Agriculture, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=fine-mapping kn-keyword=fine-mapping en-keyword=QTL kn-keyword=QTL en-keyword=reproductive stage kn-keyword=reproductive stage en-keyword=rice kn-keyword=rice en-keyword=salinity stress kn-keyword=salinity stress END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=hyag167 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Early progression after immune checkpoint inhibitor therapy in recurrent or metastatic head and neck squamous cell carcinoma: association with disease distribution in a single-center retrospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Immune checkpoint inhibitors (ICIs) are an important treatment option for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, some patients experience rapid disease progression shortly after ICI initiation, potentially resulting in deterioration of general condition and limited opportunities for subsequent treatment. This study investigated clinicopathological factors associated with early progression after ICI initiation in patients with R/M HNSCC.
Methods: We retrospectively analyzed 207 patients with R/M HNSCC treated with nivolumab or pembrolizumab at a single institution. Early progression was defined as disease progression within 90 days after ICI initiation. Associations between clinicopathological factors and early progression were evaluated using logistic regression analyses.
Results: Early progression was observed in 80 patients (38.6%). In an exploratory survival comparison, patients with early progression had significantly shorter overall survival than those without early progression. Early progression rates increased from distant-only disease to locoregional-only disease and combined locoregional and distant disease. In multivariable analysis, combined locoregional, and distant disease showed the strongest independent association with early progression. Elevated neutrophil-to-lymphocyte ratio and hypoalbuminemia were also independently associated with early progression. In contrast, treatment regimen, treatment line, number of lesions, and bulky disease were not significantly associated with early progression.
Conclusion: Disease distribution was associated with early progression after ICI initiation in patients with R/M HNSCC, with combined locoregional and distant disease showing the strongest independent association. These findings suggest that both disease status and host condition may influence failure to achieve adequate disease control shortly after ICI initiation. en-copyright= kn-copyright= en-aut-name=NodaHiroki en-aut-sei=Noda en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MakinoTakuma en-aut-sei=Makino en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NaoiYuto en-aut-sei=Naoi en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujimotoShohei en-aut-sei=Fujimoto en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=head and neck squamous cell carcinoma kn-keyword=head and neck squamous cell carcinoma en-keyword=immune checkpoint inhibitor kn-keyword=immune checkpoint inhibitor en-keyword=early progression kn-keyword=early progression en-keyword=locoregional disease kn-keyword=locoregional disease en-keyword=recurrent/metastatic disease kn-keyword=recurrent/metastatic disease END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=3 article-no= start-page=76 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel combination therapy for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma: a systematic review and network meta-analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent phase 3 randomized controlled trials (RCTs) demonstrate the promising impact of immune checkpoint inhibitor (ICI)-based combination therapies on locally advanced or metastatic urothelial carcinoma (UC). However, comparative data on the efficacy and toxicity of different ICI-based combinations are lacking. This study aims to compare the efficacy of first-line ICI-based combination therapies for locally advanced or metastatic UC using phase 3 RCT data. In November 2023, three databases were searched for RCTs evaluating oncological outcomes in patients with locally advanced or metastatic UC who were treated with first-line ICI-based combination therapies. Network meta-analysis (NMA) was conducted to compare outcomes, including overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), and treatment-related adverse events (TRAEs). Subgroup analyses were based on PD-L1 status and cisplatin eligibility. The NMA included five RCTs. Enfortumab vedotin (EV) + pembrolizumab ranked the highest for improving OS (100%), PFS (100%), ORR (96%), and CRR (96%), followed by nivolumab + chemotherapy. EV + pembrolizumab combination superiority held across PD-L1 status and cisplatin eligibility. In patients who are cisplatin-eligible, EV + pembrolizumab significantly improved OS (HR: 0.68, 95%CI 0.47–0.99) and PFS (HR: 0.67, 95%CI 0.49–0.92) compared to nivolumab + chemotherapy. Durvalumab + tremelimumab was the safest combination for severe TRAEs, and EV + pembrolizumab ranked second. Our analyses support EV + pembrolizumab combination as a first-line treatment for locally advanced or metastatic UC. Thus, EV + pembrolizumab may become a guideline-changing standard treatment. en-copyright= kn-copyright= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LaukhtinaEkaterina en-aut-sei=Laukhtina en-aut-mei=Ekaterina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=RajwaPawel en-aut-sei=Rajwa en-aut-mei=Pawel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=QuhalFahad en-aut-sei=Quhal en-aut-mei=Fahad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=PradereBenjamin en-aut-sei=Pradere en-aut-mei=Benjamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukuokayaWataru en-aut-sei=Fukuokaya en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwataniKosuke en-aut-sei=Iwatani en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=PichlerRenate en-aut-sei=Pichler en-aut-mei=Renate kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TeohJeremy Yuen-Chun en-aut-sei=Teoh en-aut-mei=Jeremy Yuen-Chun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MoschiniMarco en-aut-sei=Moschini en-aut-mei=Marco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KrajewskiWojciech en-aut-sei=Krajewski en-aut-mei=Wojciech kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MikiJun en-aut-sei=Miki en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ShariatShahrokh F. en-aut-sei=Shariat en-aut-mei=Shahrokh F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KimuraTakahiro en-aut-sei=Kimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=European Association of Urology–Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU) en-aut-sei=European Association of Urology–Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU) en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=2 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=3 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=7 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=8 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=9 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=10 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=11 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck kn-affil= affil-num=13 en-affil=S.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong kn-affil= affil-num=14 en-affil=Department of Urology, San Raffaele Hospital and Scientific Institute kn-affil= affil-num=15 en-affil=Department of Minimally Invasive and Robotic Urology, Wrocław Medical University kn-affil= affil-num=16 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=17 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=18 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=19 en-affil= kn-affil= en-keyword=Chemotherapy kn-keyword=Chemotherapy en-keyword=Enfortumab vedotin kn-keyword=Enfortumab vedotin en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors en-keyword=Metastasis kn-keyword=Metastasis en-keyword=Urothelial carcinoma kn-keyword=Urothelial carcinoma END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue= article-no= start-page=1 end-page=16 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical impact of hypomagnesemia induced by necitumumab plus cisplatin and gemcitabine treatment in patients with advanced lung squamous cell carcinoma: a subanalysis of the NINJA study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The clinical impact of hypomagnesemia induced by necitumumab plus gemcitabine and cisplatin (GCN) as a second-line or later therapy is unclear.
Objective: We aimed to evaluate the clinical characteristics and survival impact of hypomagnesemia induced by this therapy.
Design: This was a sub-analysis of the retrospective multicenter NINJA study.
Methods: Among the 93 patients enrolled in the NINJA study, this subanalysis included 75 patients with baseline serum magnesium concentrations.
Results: The incidence of grade ⩾2 hypomagnesemia was 18.0% in the patients with normal baseline serum magnesium concentrations and 42.8% in those with low concentrations (p = 0.073). The discontinuation rates of GCN treatment owing to hypomagnesemia in each group were 0% and 7.1%, respectively (p = 0.187). The number of necitumumab doses and severity of hypomagnesemia were positively correlated (r = 0.389, p < 0.001). Patients who developed hypomagnesemia in fewer than 21 days after the first dose of GCN (n = 12) had significantly poorer progression-free survival (PFS) than those without the condition (n = 63; median: 4.1 vs 4.4 months, p = 0.048). A similar trend was observed for OS (median: 9.7 vs 15.7 months, p = 0.062). These results were maintained after multivariate analyses (PFS: hazard ratio (HR) 2.46, p = 0.014; OS: HR 2.78, p = 0.021).
Conclusion: GCN as a second-line or later therapy may be tolerable regardless of the patient’s baseline serum magnesium concentration. On the other hand, early serum magnesium reduction with this therapy is associated with a poor prognosis. However, caution should be needed because our results lacked sufficient information for confounding variables other than those analyzed here that may influence the correlation between hypomagnesemia and survival. en-copyright= kn-copyright= en-aut-name=TanzawaShigeru en-aut-sei=Tanzawa en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MisumiToshihiro en-aut-sei=Misumi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyauchiEisaku en-aut-sei=Miyauchi en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MurataYasunori en-aut-sei=Murata en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeshitaMasafumi en-aut-sei=Takeshita en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KinoshitaFumihiko en-aut-sei=Kinoshita en-aut-mei=Fumihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujishitaTakatoshi en-aut-sei=Fujishita en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugawaraShunichi en-aut-sei=Sugawara en-aut-mei=Shunichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawashimaYosuke en-aut-sei=Kawashima en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HashimotoKazuki en-aut-sei=Hashimoto en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MoriMasahide en-aut-sei=Mori en-aut-mei=Masahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MiyanagaAkihiko en-aut-sei=Miyanaga en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HayashiAnna en-aut-sei=Hayashi en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TanakaHisashi en-aut-sei=Tanaka en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HondaRyoichi en-aut-sei=Honda en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NojiriMasafumi en-aut-sei=Nojiri en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SatoYuki en-aut-sei=Sato en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HataAkito en-aut-sei=Hata en-aut-mei=Akito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=IshikawaNobuhisa en-aut-sei=Ishikawa en-aut-mei=Nobuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KozukiToshiyuki en-aut-sei=Kozuki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KawamuraTakahisa en-aut-sei=Kawamura en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=SaitoGo en-aut-sei=Saito en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YamaguchiTeppei en-aut-sei=Yamaguchi en-aut-mei=Teppei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=AsadaKazuhiro en-aut-sei=Asada en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TetsumotoSatoshi en-aut-sei=Tetsumoto en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=TanakaHiroshi en-aut-sei=Tanaka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=WatanabeSatoshi en-aut-sei=Watanabe en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=UmedaYukihiro en-aut-sei=Umeda en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=YamaguchiKakuhiro en-aut-sei=Yamaguchi en-aut-mei=Kakuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=TsurunoKosuke en-aut-sei=Tsuruno en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=MisumiYuki en-aut-sei=Misumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=KuraishiHiroshi en-aut-sei=Kuraishi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=YoshiharaKen en-aut-sei=Yoshihara en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=NakaoAkira en-aut-sei=Nakao en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=KuboAkihito en-aut-sei=Kubo en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=YokoyamaToshihiko en-aut-sei=Yokoyama en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=WatanabeKana en-aut-sei=Watanabe en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=SekiNobuhiko en-aut-sei=Seki en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= affil-num=1 en-affil=Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine kn-affil= affil-num=2 en-affil=Department of Thoracic Oncology, Kansai Medical University Hospital kn-affil= affil-num=3 en-affil=Department of Data Science, National Cancer Center Hospital East kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Tohoku University Hospital kn-affil= affil-num=5 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Ichinomiya Nishi Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Ichinomiya Nishi Hospital kn-affil= affil-num=8 en-affil=Department of Thoracic Oncology, NHO Kyushu Cancer Center kn-affil= affil-num=9 en-affil=Department of Thoracic Oncology, NHO Kyushu Cancer Center kn-affil= affil-num=10 en-affil=Department of Pulmonary Medicine, Sendai Kousei Hospital kn-affil= affil-num=11 en-affil=Department of Pulmonary Medicine, Sendai Kousei Hospital kn-affil= affil-num=12 en-affil=Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center kn-affil= affil-num=13 en-affil=Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center kn-affil= affil-num=14 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=15 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=16 en-affil=Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Asahi General Hospital kn-affil= affil-num=18 en-affil=Department of Respiratory Medicine, Kanazawa Medical University kn-affil= affil-num=19 en-affil=Department of Respiratory Medicine, Kobe City Medical Center General Hospital kn-affil= affil-num=20 en-affil=Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center kn-affil= affil-num=21 en-affil=Department of Respiratory Medicine, Hiroshima Prefectural Hospital kn-affil= affil-num=22 en-affil=Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center kn-affil= affil-num=23 en-affil=Department of Thoracic Oncology, Osaka International Cancer Institute kn-affil= affil-num=24 en-affil=Department of Respirology, Graduate School of Medicine, Chiba University kn-affil= affil-num=25 en-affil=Department of Thoracic Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=26 en-affil=Department of Respiratory Medicine, Shizuoka General Hospital kn-affil= affil-num=27 en-affil=Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital kn-affil= affil-num=28 en-affil=Department of Internal Medicine, Niigata Cancer Center Hospital kn-affil= affil-num=29 en-affil=Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=30 en-affil=Department of Respiratory Medicine, Faculty of Medical Sciences, University of Fukui kn-affil= affil-num=31 en-affil=Department of Respiratory Medicine, Hiroshima University Hospital kn-affil= affil-num=32 en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center, Iwakuni, Yamaguchi, Japan kn-affil= affil-num=33 en-affil=Department of Respiratory Medicine, Iizuka Hospital kn-affil= affil-num=34 en-affil=Department of Respiratory Medicine, Yokohama Municipal Citizen’s Hospital kn-affil= affil-num=35 en-affil=Department of Pulmonary Medicine, Nagano Red Cross Hospital kn-affil= affil-num=36 en-affil=Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine kn-affil= affil-num=37 en-affil=Department of Respiratory Medicine, Fukuoka University Hospital kn-affil= affil-num=38 en-affil=Department of Respiratory Medicine and Allergology, Aichi Medical University kn-affil= affil-num=39 en-affil=Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital kn-affil= affil-num=40 en-affil=Department of Respiratory Medicine, Miyagi Cancer Center kn-affil= affil-num=41 en-affil=Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine kn-affil= en-keyword=adverse event kn-keyword=adverse event en-keyword=hypomagnesemia kn-keyword=hypomagnesemia en-keyword=lung squamous cell carcinoma kn-keyword=lung squamous cell carcinoma en-keyword=necitumumab kn-keyword=necitumumab en-keyword=prognosis kn-keyword=prognosis END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=3 article-no= start-page=276 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250307 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Influence of Educational Films on Antiviral Prescription for COVID-19: Insights from Web-Based Survey in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Prescribing antiviral agents for severe acute respiratory syndrome coronavirus 2 requires careful consideration based on the patient’s risk factors for severe disease progression and their vaccination status. However, effective interventions ensuring the appropriate use of antiviral agents by physicians have yet to be fully established. Thus, this study evaluated the impact of an educational film on antiviral prescription rates for coronavirus disease 2019 (COVID-19). Methods: This prospective, nationwide, web-based survey enrolled 1500 physicians. They were instructed to view a short educational film and assess the necessity of prescribing antiviral agents in 16 fictitious scenarios featuring adult patients with COVID-19 with varying risk factors for severe disease and vaccination statuses. We compared the antiviral prescription rates before and after viewing the educational film. Results: There was a significant increase in the antiviral prescription rates after viewing the educational film, particularly nirmatrelvir/ritonavir prescribed in cases involving immunocompromised patients (from 31.3% to 49.4%) and those with obesity (from 15.1% to 33.7%) who were unvaccinated and had no risk of drug interactions. However, viewing the educational film made little to no impact on the prescription rates for the patients with hypertension and hyperlipidemia or those with no underlying conditions. Conclusions: Short educational films may promote the appropriate use of antiviral agents for COVID-19. However, their impact on altering prescription behavior appears limited and varies according to the clinical context. en-copyright= kn-copyright= en-aut-name=KomiyaKosaku en-aut-sei=Komiya en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiwaraAkihiko en-aut-sei=Hagiwara en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShindoYuichiro en-aut-sei=Shindo en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakamatsuKazufumi en-aut-sei=Takamatsu en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimuraNaoki en-aut-sei=Nishimura en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakechiYukako en-aut-sei=Takechi en-aut-mei=Yukako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakazonoTakahiro en-aut-sei=Takazono en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IzumiShinyu en-aut-sei=Izumi en-aut-mei=Shinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GotohShimpei en-aut-sei=Gotoh en-aut-mei=Shimpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakaoSeiichiro en-aut-sei=Sakao en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IzumoTakehiro en-aut-sei=Izumo en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoKazuko en-aut-sei=Yamamoto en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YateraKazuhiro en-aut-sei=Yatera en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KakeyaHiroshi en-aut-sei=Kakeya en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShibataYoko en-aut-sei=Shibata en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TomiiKeisuke en-aut-sei=Tomii en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SagaraHironori en-aut-sei=Sagara en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SasakiYuka en-aut-sei=Sasaki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HiraiToyohiro en-aut-sei=Hirai en-aut-mei=Toyohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YokoyamaAkihito en-aut-sei=Yokoyama en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MukaeHiroshi en-aut-sei=Mukae en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=OguraTakashi en-aut-sei=Ogura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine kn-affil= affil-num=2 en-affil=Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Nagoya University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, National Center for Global Health and Medicine kn-affil= affil-num=6 en-affil=Iki-iki Clinic kn-affil= affil-num=7 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, National Center for Global Health and Medicine kn-affil= affil-num=10 en-affil=Department of Clinical Application, Center for iPS Cell, Research and Application, Kyoto University kn-affil= affil-num=11 en-affil=Department of Pulmonary Medicine, School of Medicine, International University of Health and Welfare kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Japanese Red Cross Medical Center kn-affil= affil-num=13 en-affil=Division of Infectious, Respiratory, and Digestive Medicine, First Department of Internal Medicine, University of the Ryukyus Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health, Japan kn-affil= affil-num=15 en-affil=Department of Infection Control Science, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Pulmonary Medicine, Fukushima Medical University School of Medicine kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Kobe City Medical Center General Hospital kn-affil= affil-num=18 en-affil=Department of Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine kn-affil= affil-num=19 en-affil=Center for Pulmonary Disease, National Hospital Organization Tokyo Hospital kn-affil= affil-num=20 en-affil=Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University kn-affil= affil-num=21 en-affil=Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University kn-affil= affil-num=22 en-affil=Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=23 en-affil=Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center kn-affil= en-keyword=antiviral kn-keyword=antiviral en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=prescription kn-keyword=prescription en-keyword=education kn-keyword=education END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue= article-no= start-page=1 end-page=13 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Skin disorder within 30 days is a favorable prognostic factor in patients with lung squamous cell carcinoma treated with necitumumab plus gemcitabine and cisplatin: a sub-analysis of the NINJA study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Skin disorders are major adverse events associated with necitumumab plus gemcitabine and cisplatin (Neci + GC) administration. However, the prognostic effect of skin disorders in patients with lung squamous cell carcinoma (LSCC) administered Neci + GC is unclear.
Objectives: We examined this prognostic effect in patients with LSCC, and the usefulness of minocycline administration.
Design: This was a sub-analysis of the retrospective multicenter NINJA study.
Methods: We performed a landmark survival analysis according to the presence of skin disorders at Day 30 of treatment and examined the usefulness of minocycline for treating skin disorders.
Results: Among the 93 patients, 62 (66.7%) had a skin disorder at Day 30. Nineteen, 30, and 13 patients experienced Grade 1, 2, and 3 skin disorders, respectively. The overall survival (OS) and progression-free survival (PFS) of patients with skin disorders at Day 30 were longer than those of patients without skin disorders (median OS: 434 vs 278 days, p = 0.0201; median PFS: 148 vs 82 days, p = 0.0835). Multivariable analysis showed that a skin disorder at Day 30 was an independent prognostic factor for both OS (p = 0.0044) and PFS (p = 0.0514). Of the 62 patients with skin disorders at Day 30, 38 (61.3%) were taking minocycline, and their time to treatment failure (TTF) was better than that in patients not taking minocycline (median TTF: 148 vs 101 days, p = 0.0495).
Conclusion: A skin disorder within 30 days was a favorable prognostic factor for patients with LSCC administered Neci + GC. Additionally, minocycline administration may be beneficial in patients who develop skin disorders within 30 days. en-copyright= kn-copyright= en-aut-name=KinoshitaFumihiko en-aut-sei=Kinoshita en-aut-mei=Fumihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanzawaShigeru en-aut-sei=Tanzawa en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MisumiToshihiro en-aut-sei=Misumi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyauchiEisaku en-aut-sei=Miyauchi en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MurataYasunori en-aut-sei=Murata en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeshitaMasafumi en-aut-sei=Takeshita en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamaguchiMasafumi en-aut-sei=Yamaguchi en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugawaraShunichi en-aut-sei=Sugawara en-aut-mei=Shunichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawashimaYosuke en-aut-sei=Kawashima en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HashimotoKazuki en-aut-sei=Hashimoto en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MoriMasahide en-aut-sei=Mori en-aut-mei=Masahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MiyanagaAkihiko en-aut-sei=Miyanaga en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HayashiAnna en-aut-sei=Hayashi en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TanakaHisashi en-aut-sei=Tanaka en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HondaRyoichi en-aut-sei=Honda en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NojiriMasafumi en-aut-sei=Nojiri en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SatoYuki en-aut-sei=Sato en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YamamotoKen en-aut-sei=Yamamoto en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MasudaKen en-aut-sei=Masuda en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KozukiToshiyuki en-aut-sei=Kozuki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KawamuraTakahisa en-aut-sei=Kawamura en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=SuzukiTakuji en-aut-sei=Suzuki en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YamaguchiTeppei en-aut-sei=Yamaguchi en-aut-mei=Teppei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=AsadaKazuhiro en-aut-sei=Asada en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TetsumotoSatoshi en-aut-sei=Tetsumoto en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=TanakaHiroshi en-aut-sei=Tanaka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=WatanabeSatoshi en-aut-sei=Watanabe en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=UmedaYukihiro en-aut-sei=Umeda en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=YamaguchiKakuhiro en-aut-sei=Yamaguchi en-aut-mei=Kakuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=TsurunoKosuke en-aut-sei=Tsuruno en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=MisumiYuki en-aut-sei=Misumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=KuraishiHiroshi en-aut-sei=Kuraishi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=YoshiharaKen en-aut-sei=Yoshihara en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=NakaoAkira en-aut-sei=Nakao en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=KuboAkihito en-aut-sei=Kubo en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=YokoyamaToshihiko en-aut-sei=Yokoyama en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=WatanabeKana en-aut-sei=Watanabe en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=SekiNobuhiko en-aut-sei=Seki en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, NHO Kyushu Cancer Center kn-affil= affil-num=2 en-affil=Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine kn-affil= affil-num=3 en-affil=Department of Data Science, National Cancer Center Hospital East kn-affil= affil-num=4 en-affil=Department of Thoracic Oncology, Kansai Medical University kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Tohoku University Hospital kn-affil= affil-num=6 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Ichinomiya Nishi Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Ichinomiya Nishi Hospital kn-affil= affil-num=9 en-affil=Department of Thoracic Oncology, NHO Kyushu Cancer Center kn-affil= affil-num=10 en-affil=Department of Pulmonary Medicine, Sendai Kousei Hospital kn-affil= affil-num=11 en-affil=Department of Pulmonary Medicine, Sendai Kousei Hospital kn-affil= affil-num=12 en-affil=Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center kn-affil= affil-num=13 en-affil=Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center kn-affil= affil-num=14 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=15 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=16 en-affil=Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Asahi General Hospital kn-affil= affil-num=18 en-affil=Department of Respiratory Medicine, Kanazawa Medical University kn-affil= affil-num=19 en-affil=Department of Respiratory Medicine, Kobe City Medical Center General Hospital kn-affil= affil-num=20 en-affil=Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center kn-affil= affil-num=21 en-affil=Department of Respiratory Medicine, Hiroshima Prefectural Hospital kn-affil= affil-num=22 en-affil=Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center kn-affil= affil-num=23 en-affil=Department of Thoracic Oncology, Osaka International Cancer Institute kn-affil= affil-num=24 en-affil=Department of Respirology, Graduate School of Medicine, Chiba University kn-affil= affil-num=25 en-affil=Department of Thoracic Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=26 en-affil=Department of Respiratory Medicine, Shizuoka General Hospital kn-affil= affil-num=27 en-affil=Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital kn-affil= affil-num=28 en-affil=Department of Internal Medicine, Niigata Cancer Center Hospital kn-affil= affil-num=29 en-affil=Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=30 en-affil=Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui kn-affil= affil-num=31 en-affil=Department of Respiratory Medicine, Hiroshima University Hospital kn-affil= affil-num=32 en-affil=Department of Respiratory medicine, NHO Iwakuni Clinical Center kn-affil= affil-num=33 en-affil=Department of Respiratory Medicine, Iizuka Hospital kn-affil= affil-num=34 en-affil=Department of Respiratory Medicine, Yokohama Municipal Citizen’s Hospital kn-affil= affil-num=35 en-affil=Department of Respiratory Medicine, Nagano Red Cross Hospital kn-affil= affil-num=36 en-affil=Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine kn-affil= affil-num=37 en-affil=Department of Respiratory Medicine, Fukuoka University Hospital kn-affil= affil-num=38 en-affil=Department of Respiratory Medicine and Allergology, Aichi Medical University School of Medicine kn-affil= affil-num=39 en-affil=Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital kn-affil= affil-num=40 en-affil=Department of Respiratory Medicine, Miyagi Cancer Center kn-affil= affil-num=41 en-affil=Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine kn-affil= en-keyword=adverse event kn-keyword=adverse event en-keyword=lung cancer kn-keyword=lung cancer en-keyword=necitumumab kn-keyword=necitumumab en-keyword=skin disorder kn-keyword=skin disorder en-keyword=squamous cell carcinoma kn-keyword=squamous cell carcinoma END start-ver=1.4 cd-journal=joma no-vol=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=11 cd-vols= no-issue=1 article-no= start-page=26 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Incidence and survival outcomes of myocarditis and pericardial diseases associated with immune checkpoint inhibitor therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Immune checkpoint inhibitor(ICI) induced cardiac immune related adverse events are challenging to study; Leveraging large data bases like TriNetX global health network may provide needed insights.
Methods We performed a retrospective cohort study including patients diagnosed neoplasm and 18 and older when receiving ICI therapy from 1/1/2011 to 12/31/2022. Queried ICD 9/10 codes identified patients experiencing myocarditis, pericarditis, pericardial effusion, and cardiac tamponade within 1 year of ICI initiation. Survival analyses compared one-year overall survival (OS) of patients experiencing cardiac irAEs against propensity score matched populations not experiencing them.
Results In 88,928 identified ICI patients, the incidence of myocarditis(0.48%), pericarditis(0.22%), and cardiac tamponade(0.47%) were less than 1% while pericardial effusion occurred in 4.71% of patients. Hazard ratios (HRs) were significantly higher in all cardiac irAE groups: myocarditis (HR:1.26, 95% CI:1.04–1.54, p = 0.02), pericarditis (HR:1.36, 95% CI:1.02–1.82, p = 0.04), pericardial effusion (HR:1.49, 95% CI:1.39–1.59, p < 0.0001), cardiac tamponade (HR:2.15, 95% CI:1.79–2.57, p < 0.0001), and overall pericardial disease (HR:1.46, 95% CI:1.37–1.56, p < 0.0001). There was no significant difference in OS between myocarditis and pericarditis or overall pericardial diseases.
Discussion/conclusion Utilizing a uniquely large cohort of ICI patients, this study further shows the rarity of cardiac inflammatory irAEs and highlights their significant impact on patient survival. en-copyright= kn-copyright= en-aut-name=OzakiAya F. en-aut-sei=Ozaki en-aut-mei=Aya F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SayerMichael en-aut-sei=Sayer en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagasakaMisako en-aut-sei=Nagasaka en-aut-mei=Misako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LeeBenjamin J. en-aut-sei=Lee en-aut-mei=Benjamin J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DohJean en-aut-sei=Doh en-aut-mei=Jean kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaqviAli en-aut-sei=Naqvi en-aut-mei=Ali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NowrouziNareh en-aut-sei=Nowrouzi en-aut-mei=Nareh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=PatelPranav M. en-aut-sei=Patel en-aut-mei=Pranav M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= affil-num=2 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= affil-num=3 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Hematology and Oncology, University of California kn-affil= affil-num=5 en-affil=Department of Pharmacy, University of California kn-affil= affil-num=6 en-affil=Department of Pharmacy, University of California kn-affil= affil-num=7 en-affil=Division of Cardiology, Department of Medicine, University of California kn-affil= affil-num=8 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= affil-num=9 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=10 en-affil=Division of Cardiology, Department of Medicine, University of California kn-affil= en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors en-keyword=Myocarditis kn-keyword=Myocarditis en-keyword=Cardiotoxicity kn-keyword=Cardiotoxicity en-keyword=Immune-related adverse events kn-keyword=Immune-related adverse events en-keyword=Overall survival kn-keyword=Overall survival END start-ver=1.4 cd-journal=joma no-vol=100 cd-vols= no-issue=4 article-no= start-page=592 end-page=605 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250125 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exploring the Clinical Diversity of Castleman Disease and TAFRO Syndrome: A Japanese Multicenter Study on Lymph Node Distribution Patterns en-subtitle= kn-subtitle= en-abstract= kn-abstract=Individuals diagnosed with Castleman disease (CD) and TAFRO syndrome (characterized by thrombocytopenia, anasarca, fever, bone marrow fibrosis, and organomegaly) displays a wide range of clinical symptoms, including varying patterns of lymph node enlargement, systemic inflammation, and impaired organ function. Some patients may present with both CD and TAFRO syndrome concurrently. A retrospective study conducted across multiple centers in Japan examined 321 cases to determine if the quantity and position of swollen lymph nodes could forecast the clinical progression and intensity of these conditions. Interestingly, the study revealed that patients with TAFRO syndrome exhibited lymphadenopathy across all ranges of lymph node region counts. Moreover, no specific clinical patterns were associated with the number of affected lymph node regions in CD patients, regardless of whether they also had TAFRO syndrome. These results enhance our understanding of the clinical variability in CD and TAFRO syndrome, suggesting that a comprehensive clinical evaluation, rather than relying solely on lymph node count, is crucial for effectively managing these conditions. Additional studies are required to establish reliable diagnostic markers and to predict disease severity at the time of diagnosis, ultimately improving patient outcomes. en-copyright= kn-copyright= en-aut-name=OtsukaMizuna en-aut-sei=Otsuka en-aut-mei=Mizuna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KogaTomohiro en-aut-sei=Koga en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SumiyoshiRemi en-aut-sei=Sumiyoshi en-aut-mei=Remi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukuiShoichi en-aut-sei=Fukui en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanekoYuko en-aut-sei=Kaneko en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimizuTakayuki en-aut-sei=Shimizu en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatsubeAtsushi en-aut-sei=Katsube en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YanoShingo en-aut-sei=Yano en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MasakiYasufumi en-aut-sei=Masaki en-aut-mei=Yasufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IdeMakoto en-aut-sei=Ide en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshifujiHajime en-aut-sei=Yoshifuji en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KitanoMasayasu en-aut-sei=Kitano en-aut-mei=Masayasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SawaNaoki en-aut-sei=Sawa en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NiiroHiroaki en-aut-sei=Niiro en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NakamuraNaoya en-aut-sei=Nakamura en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FajgenbaumDavid C. en-aut-sei=Fajgenbaum en-aut-mei=David C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=van RheeFrits en-aut-sei=van Rhee en-aut-mei=Frits kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KawakamiAtsushi en-aut-sei=Kawakami en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=2 en-affil=Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=3 en-affil=Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=4 en-affil=Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=5 en-affil=Division of Rheumatology, Department of Internal Medicine Keio University School of Medicine Tokyo Japan kn-affil= affil-num=6 en-affil=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine kn-affil= affil-num=8 en-affil=Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine kn-affil= affil-num=9 en-affil=Department of Hematology and Immunology, Kanazawa Medical University kn-affil= affil-num=10 en-affil=Department of Hematology, Takamatsu Red Cross Hospital kn-affil= affil-num=11 en-affil=DDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=12 en-affil=Department of Collagen Disease and Rheumatology, Sumitomo Hospital kn-affil= affil-num=13 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=14 en-affil=Nephrology Center and Department of Rheumatology, Toranomon Hospital Kajigaya kn-affil= affil-num=15 en-affil=Department of Clinical Immunology and Rheumatology/Infectious Disease, Kyushu University Hospital kn-affil= affil-num=16 en-affil=Department of Pathology, Tokai University School of Medicine kn-affil= affil-num=17 en-affil=Center for Cytokine Storm Treatment & Laboratory, University of Pennsylvania kn-affil= affil-num=18 en-affil=Myeloma Center, University of Arkansas for Medical Sciences kn-affil= affil-num=19 en-affil=Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences kn-affil= en-keyword=Castleman disease kn-keyword=Castleman disease en-keyword=clinical variability kn-keyword=clinical variability en-keyword=lymph node distribution kn-keyword=lymph node distribution en-keyword=multicenter cohort kn-keyword=multicenter cohort en-keyword=TAFRO syndrome kn-keyword=TAFRO syndrome 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=31 cd-vols= no-issue=6 article-no= start-page=e70681 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bridging the Awareness–Action Gap in Disaster Preparedness: A Qualitative Study of Immersive Virtual Reality Learning Among Nursing Students en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Disasters increasingly challenge healthcare systems, highlighting the need to strengthen preparedness among future healthcare professionals. Although disaster risk awareness is important, it does not consistently translate into preparedness behaviours, reflecting the awareness–action gap. Immersive virtual reality (VR) may enhance experiential disaster learning, but how it influences preparedness processes remains insufficiently understood, particularly in healthcare and critical care education.
Aims: To explore how immersive VR-based disaster simulations influence disaster risk perception and preparedness among nursing students, with particular attention to the awareness–action gap and implications for future healthcare and critical care practice.
Study Design: A qualitative descriptive study using immersive VR-based disaster simulations followed by semi-structured interviews. Twelve undergraduate and graduate nursing students in Japan experienced immersive VR simulations depicting floods and landslides. Individual semi-structured interviews explored emotional responses, disaster risk perception, preparedness awareness and anticipated behavioural responses. Data were analysed using Krippendorff's content analysis with researcher triangulation.
Results: Five categories were identified: (1) heightened vulnerability and psychological burden through immersion; (2) persistence of the awareness–action gap despite increased risk perception; (3) enhanced risk recognition and preparedness intentions; (4) recognition of the need for social and structural support systems; and (5) emerging responsibility accompanied by perceived limitations. VR transformed abstract disaster risk into emotionally salient experiences, strengthening threat appraisal and preparedness awareness; however, awareness did not consistently translate into preparedness behaviours, reflecting insufficient coping appraisal and self-efficacy.
Conclusions: Immersive VR may strengthen disaster risk perception and preparedness awareness, but immersive experiences alone may be insufficient to bridge the awareness–action gap. Combining VR with reflective learning, skills-based training and collaborative simulation may strengthen coping appraisal and preparedness action.
Relevance to Clinical Practice: Immersive VR combined with reflective and skills-based learning may support psychological readiness, situational awareness and disaster preparedness competencies among future nurses, including those preparing for critical care practice. en-copyright= kn-copyright= en-aut-name=MoriKeiko en-aut-sei=Mori en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamazakiMiina en-aut-sei=Yamazaki en-aut-mei=Miina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HarunaYoshiyuki en-aut-sei=Haruna en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Kobe University Hospital kn-affil= affil-num=3 en-affil=Snowlion. Inc. kn-affil= en-keyword=awareness–action gap kn-keyword=awareness–action gap en-keyword=critical care nursing kn-keyword=critical care nursing en-keyword=disaster preparedness kn-keyword=disaster preparedness en-keyword=disaster risk perception kn-keyword=disaster risk perception en-keyword=nursing students kn-keyword=nursing students en-keyword=simulation-based education kn-keyword=simulation-based education en-keyword=virtual reality kn-keyword=virtual reality END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=18 article-no= start-page=8117 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260912 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Salivary miR-324-5p Is Associated with Periodontal Inflamed Surface Area in People Living with HIV Receiving Antiretroviral Therapy: A Case–Control Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontitis is a common inflammatory disease that affects the tooth-supporting tissues. Salivary microRNA (miRNA) expression in extracellular vesicles (EVs) can reflect periodontal status. Both the prevalence and severity of periodontitis are higher in people with human immunodeficiency virus (PWH). This study aimed to identify miRNA in salivary EVs associated with periodontitis in PWH receiving antiretroviral therapy (ART). The case group comprised PWH with periodontitis undergoing ART, while the control group included individuals with periodontitis but without HIV infection. The study was conducted in two phases. In the first phase, a specific miRNA was identified in the case group using next-generation sequencing analysis, resulting in the selection of hsa-miR-324-5p as a candidate marker of periodontitis. In the second phase, the association between miRNA expression of hsa-miR-324-5p and periodontal status in the case group was evaluated using real-time-quantitative PCR (RT-qPCR). RT-qPCR analysis demonstrated that hsa-miR-324-5p expression was significantly associated with periodontal inflamed surface area (PISA). Bioinformatic analysis identified 10 potential hub genes for hsa-miR-324-5p that are involved in protein kinase binding and are associated with the adherens junction pathway, that may be contributing to the pathogenesis of periodontitis. Salivary hsa-miR-324-5p derived from EVs may be associated with the severity of periodontitis among PWH receiving ART. en-copyright= kn-copyright= en-aut-name=NurhamimMohammad en-aut-sei=Nurhamim en-aut-mei=Mohammad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokoiAya en-aut-sei=Yokoi en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaruyamaTakayuki en-aut-sei=Maruyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=miR-324-5p kn-keyword=miR-324-5p en-keyword=saliva kn-keyword=saliva en-keyword=marker kn-keyword=marker en-keyword=HIV kn-keyword=HIV en-keyword=periodontitis kn-keyword=periodontitis en-keyword= extracellular vesicles kn-keyword= extracellular vesicles en-keyword=inflammation kn-keyword=inflammation END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=6 article-no= start-page=e117719 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=Association between venous access-site closure device use and postoperative nausea and vomiting after atrial fibrillation ablation under propofol sedation: a single-centre retrospective observational study in Okayama, Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives To examine whether the use of a venous access-site closure device is associated with the occurrence of postoperative nausea and vomiting (PONV) after atrial fibrillation (AF) ablation under propofol sedation.
Design Observational study.
Setting A single-centre retrospective observational study in Okayama, Japan.
Participants We retrospectively analysed consecutive patients who underwent AF ablation under deep propofol sedation with adaptive servo-ventilation. A total of 686 patients were included. Patients were managed using a standardised sedation protocol with or without low-dose pentazocine. Patients treated with conventional manual compression for haemostasis (n=383) were compared with those treated using a venous access-site closure device (n=303).
Interventions Postprocedural bed rest duration and the incidence and timing of PONV were compared between groups. Associations between closure device use and PONV were evaluated using logistic regression analysis.
Primary outcome measure The primary outcome was the occurrence of PONV following AF ablation.
Results All procedures were completed under propofol sedation without conversion to general anaesthesia. The duration of postprocedural bed rest was shorter in the device group than in the conventional-compression group (mean difference −14.7 hours, 95% CI −15.2 to −14.0).
PONV occurred in 6/303 patients (2.0%) in the device group and 20/383 patients (5.2%) in the conventional-compression group, corresponding to a relative risk of 0.38 (95% CI 0.15 to 0.93), an OR 0.25 (95% CI 0.10 to 0.62) and a risk difference of −3.2% (95% CI −6.0% to −0.5%).
In multivariable analysis, use of a venous closure device was associated with a lower likelihood of PONV.
Conclusions In this single-centre observational study, use of a venous access-site closure device was associated with a lower occurrence of PONV after AF ablation under propofol sedation. These findings suggest that postprocedural management strategies enabling earlier mobilisation may be associated with improved patient comfort; however, causal inference is limited by the observational design. en-copyright= kn-copyright= en-aut-name=SakanoueHaruna en-aut-sei=Sakanoue en-aut-mei=Haruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamajiHirosuke en-aut-sei=Yamaji en-aut-mei=Hirosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkamotoSayaka en-aut-sei=Okamoto en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkanoKumi en-aut-sei=Okano en-aut-mei=Kumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujitaYuka en-aut-sei=Fujita en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigashiyaShunichi en-aut-sei=Higashiya en-aut-mei=Shunichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MurakamiTakashia en-aut-sei=Murakami en-aut-mei=Takashia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=KusachiShozo en-aut-sei=Kusachi en-aut-mei=Shozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Nursing, Okayama Heart Clinic kn-affil= affil-num=2 en-affil=Heart Rhythm Centre, Okayama Heart Clinic kn-affil= affil-num=3 en-affil=Department of Nursing, Okayama Heart Clinic kn-affil= affil-num=4 en-affil=Department of Nursing, Okayama Heart Clinic kn-affil= affil-num=5 en-affil=Department of Nursing, Okayama Heart Clinic kn-affil= affil-num=6 en-affil=Heart Rhythm Centre, Okayama Heart Clinic kn-affil= affil-num=7 en-affil=Heart Rhythm Centre, Okayama Heart Clinic kn-affil= affil-num=8 en-affil=Graduate School of Health Sciences, Department of Medical Technology, Okayama University kn-affil= affil-num=9 en-affil=Heart Rhythm Centre, Okayama Heart Clinic kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=3 article-no= start-page=ofaf118 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Amikacin Liposome Inhalation Suspension and Amikacin Resistance Development in Patients With Refractory Mycobacterium avium Complex Pulmonary Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background. Amikacin liposome inhalation suspension (ALIS) is key for treating refractory Mycobacterium avium complex pulmonary disease (MAC-PD). However, microbiological efficacy by subtype remains unknown. The frequency and mechanism of amikacin (AMK) resistance during ALIS administration are also unclear.
Methods. We retrospectively analyzed data from refractory MAC-PD patients who received ALIS for at least 6 months as an adjunct to guideline-based therapy at the NHO Kinki Chuo Chest Medical Center. We investigated the efficacy of ALIS and analyzed gene expression and the frequency of AMK resistance.
Results. We enrolled 44 patients (median age, 72.0 years): 19 (43.2%) with the noncavitary nodular bronchiectatic (NC-NB) subtype and 25 (56.8%) with the cavitary subtype. Overall, sputum culture conversion was 56.8% (25/44): 84.2% (16/19) in the NC-NB subtype and 36.0% (9/25) in the cavitary subtype (P = .001). During intermittent dosing, conversion occurred in 50.0% (9/18). In patients with C-reactive protein (CRP) ≥1 mg/dL, cavitary subtype, and clarithromycin (CLM) resistance, the risk ratio for persistently positive cultures was 10.81 (95% CI, 1.66–70.40) compared with those with CRP <1 mg/dL, NC-NB subtype, and CLM susceptibility. Of all participants, 15.9% (7/44) had isolates with AMK resistance (minimum inhibitory concentration ≥128 µg/mL), and of these 71.4% (5/7) had rrs mutations.
Conclusions. Regimens that included ALIS achieved higher culture conversion in NC-NB than cavitary MAC-PD cases. High CRP levels, cavitary disease, and CLM resistance predicted persistent culture positivity. AMK resistance acquired during ALIS administration may limit treatment options for refractory MAC-PD. en-copyright= kn-copyright= en-aut-name=KuraharaYu en-aut-sei=Kurahara en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaShiomi en-aut-sei=Yoshida en-aut-mei=Shiomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OsugiAsami en-aut-sei=Osugi en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaYuya en-aut-sei=Tanaka en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiTakehiko en-aut-sei=Kobayashi en-aut-mei=Takehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawasakiYohei en-aut-sei=Kawasaki en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MitaraiSatoshi en-aut-sei=Mitarai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsuyuguchiKazunari en-aut-sei=Tsuyuguchi en-aut-mei=Kazunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center kn-affil= affil-num=2 en-affil=Clinical Research Center, NHO Kinki Chuo Chest Medical Center , Osaka , kn-affil= affil-num=3 en-affil=Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=4 en-affil=Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center kn-affil= affil-num=5 en-affil=Clinical Research Center, NHO Kinki Chuo Chest Medical Center kn-affil= affil-num=6 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Biostatistics, Graduate School of Medicine, Saitama Medical University kn-affil= affil-num=8 en-affil=Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=9 en-affil=Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center kn-affil= en-keyword=amikacin liposome inhalation suspension kn-keyword=amikacin liposome inhalation suspension en-keyword=Mycobacterium avium complex kn-keyword=Mycobacterium avium complex en-keyword=noncavitary-nodular bronchiectatic kn-keyword=noncavitary-nodular bronchiectatic en-keyword=amikacin resistance kn-keyword=amikacin resistance en-keyword=rrs mutation kn-keyword=rrs mutation END start-ver=1.4 cd-journal=joma no-vol=49 cd-vols= no-issue=8 article-no= start-page=1285 end-page=1290 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260825 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Adjusted Creatinine Clearance on Carboplatin Dosing in Endometrial Cancer: A Retrospective Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Carboplatin (CBDCA) dosing is commonly determined using the Calvert formula, with creatinine clearance (Ccr) estimated by the Cockcroft–Gault formula. In Japan, where serum creatinine (sCr) is usually measured enzymatically, unadjusted Ccr may overestimate glomerular filtration rate and lead to CBDCA overdosing. We retrospectively compared treatment exposure, hematologic toxicity, and exploratory oncologic outcomes in patients with endometrial cancer who received postoperative paclitaxel plus CBDCA therapy. Patients were grouped according to whether CBDCA dosing was based on the conventional Cockcroft–Gault formula (CG group) or on adjusted Ccr calculated by adding 0.2 mg/dL to sCr (adjusted group). The incidence of Grade ≥3 neutropenia was significantly lower in the adjusted group than in the CG group. The 5-year progression-free survival (PFS) rate was numerically lower in the adjusted group than in the CG group, although no statistically significant difference was observed between the groups. Because the number of PFS events was limited, the effect of adjusted Ccr-based dosing on oncologic outcomes remains uncertain. These findings suggest that adjusted Ccr-based dosing may reduce hematologic toxicity in routine clinical practice. However, given the limited number of PFS events and the wide uncertainty in survival estimates, further studies are needed to clarify its impact on oncologic outcomes. en-copyright= kn-copyright= en-aut-name=KatayamaKentaro en-aut-sei=Katayama en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ImamuraMakio en-aut-sei=Imamura en-aut-mei=Makio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UeharaTakashi en-aut-sei=Uehara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Clinical Support, Kurashiki Medical Center kn-affil= affil-num=3 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=carboplatin kn-keyword=carboplatin en-keyword=creatinine clearance kn-keyword=creatinine clearance en-keyword=dose adjustment kn-keyword=dose adjustment en-keyword=endometrial cancer kn-keyword=endometrial cancer en-keyword=neutropenia kn-keyword=neutropenia en-keyword=pharmaceutical care kn-keyword=pharmaceutical care END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=6 article-no= start-page=e110118 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Routine Generative AI Use and Acceptance of Medical AI: A Cross-Sectional Survey of Healthcare Workers and the Public in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Acceptance of medical artificial intelligence (AI) is critical for successful implementation, yet its acceptance may vary by clinical application and stakeholder group. Whether routine use of generative AI (GAI) is associated with acceptance of medical AI remains unclear.
Methods
A cross-sectional web survey was conducted in Japan in November 2025 using web-panel convenience sampling from an online research panel. The small analytic sample comprised 200 participants aged 20-69 years, including 100 healthcare workers and 100 non-healthcare workers. GAI use was assessed using two five-point items (GAI use at work and in daily life) and dichotomized as at least monthly use in either daily life or work versus less than monthly use in both settings, based on prespecified criteria. Acceptance of medical AI was measured for five scenario-based applications - AI-assisted imaging interpretation, AI-based health risk prediction, AI-based treatment recommendations, AI-enabled triage guidance, and AI-assisted robotic surgery - using a four-point acceptability scale; responses were dichotomized as acceptable versus not acceptable. Calibration weights were constructed to approximate Japanese internet users by raking on sex-by-age group and household income, normalized to the analytic sample size, and truncated at prespecified bounds. Adjusted prevalence ratios (aPRs) were estimated using modified Poisson regression with robust standard errors, stratified by occupation; covariates were selected a priori using a modified disjunctive cause criterion. This study was exploratory; therefore, adjustments for multiple comparisons were not performed.
Results
Among healthcare workers, the lower-use group had a higher prevalence of non-acceptance of AI-based health risk prediction (aPR 6.980, 95% CI 1.412-34.506) and AI-based treatment recommendations (aPR 4.364, 95% CI 1.331-14.305), whereas estimates for imaging interpretation, triage guidance, and robotic surgery remained statistically uncertain. Among non-healthcare workers, the lower-use group had a higher prevalence of non-acceptance of AI-assisted imaging interpretation (aPR 13.906, 95% CI 1.624-119.052), AI-based health risk prediction (aPR 4.861, 95% CI 1.133-20.862), AI-based treatment recommendations (aPR 6.288, 95% CI 1.386-28.530), and AI-assisted robotic surgery (aPR 6.173, 95% CI 1.435-26.561); the adjusted estimate for AI-enabled triage guidance was not statistically supported (aPR 1.840, 95% CI 0.521-6.505). Several estimates had wide confidence intervals, indicating substantial imprecision.
Conclusions
In this small exploratory web-panel convenience sample, lower-frequency GAI use was associated with higher non-acceptance of several medical AI applications. Associations were observed across more applications among non-healthcare workers than among healthcare workers. Because the study was cross-sectional, used convenience sampling, and included imprecise estimates with wide confidence intervals, the findings should not be interpreted causally. Larger studies using longitudinal or interventional designs are needed to clarify temporality and mechanisms. en-copyright= kn-copyright= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Center for Innovative Clinical Medicine, Medical Development Field, Okayama University kn-affil= en-keyword=generative ai kn-keyword=generative ai en-keyword=healthcare workers kn-keyword=healthcare workers en-keyword=medical ai kn-keyword=medical ai en-keyword=non-healthcare workers kn-keyword=non-healthcare workers en-keyword=technology acceptance kn-keyword=technology acceptance en-keyword=web-based survey kn-keyword=web-based survey END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=60 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260920 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Carbon solubility and liquid–liquid immiscibility in Fe–C–S ternary system up to 6 GPa: implications for the core of small planetary bodies en-subtitle= kn-subtitle= en-abstract= kn-abstract=High-pressure, high-temperature experiments were conducted in a multi-anvil press using seven different starting compositions to investigate the phase relations of Fe–C–S liquids at pressures up to 6 GPa and temperatures up to 2000 K. Quenched samples revealed immiscible C-rich and S-rich metallic liquids at 2 and 4 GPa, manifesting as either large immiscible zones or emulsified smaller droplets. On the contrary, no immiscibility was observed at 5 or 6 GPa. At these higher pressures, the carbon solubility limit, significantly reduced by increasing sulfur content in the ternary liquid, prevents the formation of a liquid phase rich in both C and S. Our findings thus indicate that super-liquidus immiscibility in Fe-rich compositions does not occur at pressures above 5 GPa, due to the differential pressure dependence of C solubility and miscibility. The limited C solubility in S-rich liquids at higher pressures effectively suppresses immiscibility. Based on these results, terrestrial planetary bodies with fluid cores at pressures exceeding 5 GPa are unlikely to experience liquid–liquid immiscibility, even when both carbon and sulfur are abundant, as sulfur limits carbon solubility and promotes its exsolution. For the Moon, immiscibility-induced core stratification is not expected, though local emulsification could occur near the core–mantle boundary (CMB). In smaller bodies, a two-liquid Fe–C–S core may form at high temperatures, but progressive cooling may lead to graphite crystallization and the potential development of a graphitic crust. en-copyright= kn-copyright= en-aut-name=ZhaoBin en-aut-sei=Zhao en-aut-mei=Bin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MorardGuillaume en-aut-sei=Morard en-aut-mei=Guillaume kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ManthilakeGeeth en-aut-sei=Manthilake en-aut-mei=Geeth kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ParisiadesParaskevas en-aut-sei=Parisiades en-aut-mei=Paraskevas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YangJing en-aut-sei=Yang en-aut-mei=Jing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FeiYingwei en-aut-sei=Fei en-aut-mei=Yingwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Le GodecYann en-aut-sei=Le Godec en-aut-mei=Yann kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KondoNozomi en-aut-sei=Kondo en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshinoTakashi en-aut-sei=Yoshino en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AntonangeliDaniele en-aut-sei=Antonangeli en-aut-mei=Daniele kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=UMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne Université kn-affil= affil-num=3 en-affil=Laboratoire Magmas et Volcans, Université Clermont-Auvergne kn-affil= affil-num=4 en-affil=UMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne Université kn-affil= affil-num=5 en-affil=Earth and Planets Laboratory, Carnegie Institution for Science kn-affil= affil-num=6 en-affil=Earth and Planets Laboratory, Carnegie Institution for Science kn-affil= affil-num=7 en-affil=UMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne Université kn-affil= affil-num=8 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=9 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=10 en-affil=UMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne Université kn-affil= en-keyword=Iron–carbon–sulfur liquids kn-keyword=Iron–carbon–sulfur liquids en-keyword=Miscibility kn-keyword=Miscibility en-keyword=High pressure and high temperature kn-keyword=High pressure and high temperature en-keyword=Planetary cores kn-keyword=Planetary cores END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e00714-26 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260915 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Interaction with the N-acetylgalactosamine moiety facilitates pore formation by Cry4Aa toxin, thereby increasing its toxicity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cry4Aa is a mosquito-larvicidal toxin produced by Bacillus thuringiensis serovar israelensis. Cry4Aa exhibits a characteristic architecture comprising three domains (I, II, and III) and functions as a pore-forming toxin, consistent with many previously reported insecticidal Cry toxins. However, the mechanism preceding pore formation by Cry4Aa, including receptor recognition, remains to be elucidated. The present study examined the potential involvement of sugar moieties in the Cry4Aa mode of action, with a particular focus on the process of pore formation. Cry4Aa and the sugar N-acetylgalactosamine exhibited considerably increased binding affinity. Furthermore, N-acetylgalactosamine treatment significantly enhanced the toxicity of Cry4Aa against Culex pipiens mosquito larvae. In the presence of N-acetylgalactosamine, the binding of Cry4Aa to phosphatidylcholine liposomes increased by 1.4-fold. The presence of this sugar did not affect the single-channel conductance of Cry4Aa pores formed in artificial lipid bilayers; however, it did appear to increase the number of Cry4Aa pores per designated area. In silico molecular docking analysis revealed promising binding sites within the cavity, surrounded by the Cry4Aa domains. These results suggest that the interaction of Cry4Aa with N-acetylgalactosamine moieties is a vital step in the process of pore formation. This interaction may induce a conformational change in the Cry4Aa molecule that facilitates its insertion into the target membrane. en-copyright= kn-copyright= en-aut-name=HowladerMohammad Tofazzal Hossain en-aut-sei=Howlader en-aut-mei=Mohammad Tofazzal Hossain kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsutsuiTaiyo en-aut-sei=Tsutsui en-aut-mei=Taiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SaitoKouichi en-aut-sei=Saito en-aut-mei=Kouichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HayakawaTohru en-aut-sei=Hayakawa en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Entomology, Bangladesh Agricultural University kn-affil= affil-num=2 en-affil=Applied Chemistry and Biotechnology Program, School of Engineering, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Applied Chemistry and Biotechnology Program, School of Engineering, Okayama University kn-affil= en-keyword=Bacillus thuringiensisser serovar israelensis kn-keyword=Bacillus thuringiensisser serovar israelensis en-keyword=Cry4Aa toxin kn-keyword=Cry4Aa toxin en-keyword=Culex pipiens mosquito larvae kn-keyword=Culex pipiens mosquito larvae en-keyword=interaction with N-acetylgalactosamine kn-keyword=interaction with N-acetylgalactosamine END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue= article-no= start-page=485 end-page=494 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202611 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enhancement of mechanical properties in a cast hypereutectic Al–Si alloy via rapid cooling in heated mold continuous casting en-subtitle= kn-subtitle= en-abstract= kn-abstract=To enhance mechanical properties in cast hypereutectic Al–Si alloys, Al–14.5Si samples were produced by the heated mold continuous casting (HMC). The HMC process was conducted under unidirectional solidification at cooling rates (CRs) ranging from 4.6 × 10−1 to 1.3 × 103 K/s, which were obtained by controlling the casting speed (CS). The microstructure basically consisted of α-Al dendrite, Al–Si eutectic and primary Si, while their area fractions (fα-Al, fe, and fp-Si) varied depending on the CR. At the low CR of 4.6 × 10−1 K/s, their area fractions were as follows: fα-Al = 0.2%, fe = 97.3%, and fp-Si = 2.5%, which is the typical microstructural morphology of a hypereutectic Al-Si alloy. In contrast, at the high CR of 1.3 × 103 K/s, those area fractions were altered to fα-Al = 32.3% and fe = 67.7%, while primary Si was strongly suppressed (fp-Si ≈ 0%) despite the hypereutectic Al–14.5Si alloy. Moreover, at the high CR, the aluminum matrix appears to exhibit a nearly uniform crystal orientation along <101>. These microstructural changes may be related not only to high CR but also the difference in growth kinetics between primary Si and α-Al dendrites. Accordingly, an apparent eutectic composition shifted from 12.6 to 19.7 wt% Si. The atypical microstructural formation led to a significant improvement in the tensile properties: the ultimate tensile strength of 400 MPa and fracture strain of 17%. These tensile properties are more than twice those of the conventional cast hypereutectic Al–14.5Si alloy. en-copyright= kn-copyright= en-aut-name=TakeuchiShuhei en-aut-sei=Takeuchi en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakagawaShota en-aut-sei=Nakagawa en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShinzatoYoshifumi en-aut-sei=Shinzato en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MinodaTadashi en-aut-sei=Minoda en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtsukaNaotaka en-aut-sei=Ohtsuka en-aut-mei=Naotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkayasuMitsuhiro en-aut-sei=Okayasu en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=UACJ Corporation kn-affil= affil-num=3 en-affil=UACJ Corporation kn-affil= affil-num=4 en-affil=UACJ Corporation kn-affil= affil-num=5 en-affil=UACJ Corporation kn-affil= affil-num=6 en-affil=Department of Mechanical and Systems Engineering, Okayama University kn-affil= en-keyword=Hypereutectic Al–Si alloy kn-keyword=Hypereutectic Al–Si alloy en-keyword=Heated mold continuous casting kn-keyword=Heated mold continuous casting en-keyword=Mechanical property kn-keyword=Mechanical property en-keyword=Microstructural characteristics kn-keyword=Microstructural characteristics en-keyword=Supercooling kn-keyword=Supercooling END start-ver=1.4 cd-journal=joma no-vol=1868 cd-vols= no-issue=1 article-no= start-page=149607 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2027 dt-pub=202701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural and functional analysis of a photosystem II mutant PsbA3-S264V en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosystem II (PSII) catalyzes water oxidation and oxygen evolution by a light-induced electron transfer chain, leading to the generation of electrons, protons and dioxygen. D1-S264 is a residue located close to the QB-binding site, and mutation of this residue has been shown to bring significant effects on the electron transfer and oxygen-evolving activities. Here we analyzed the structure of a Thermosynechococcus elongatus mutant PsbA3-S264V by cryo-electron microscopy at 1.96 Å resolution, which showed significant changes in the structure surrounding the bicarbonate and QB-binding region. Due to change of Ser to Val, the hydrogen-bond between the QB carbonyl oxygen and S264 is altered, which changed the protonation pathway of QB from the original route of D1-H252 through D1-S264 to QB, to a new, longer and less efficient route of D1-H252 through D1-F265 to QB. Two residues, D1-E244 and D2-E242, changed their side chain orientations significantly. Among them, D2-E242 adopted two conformations, and both are largely deviated from the original structure. All these changes led to alterations in hydrogen-bonding networks of two channels, channel A and channel B, that connect the stromal surface to QB and may function to transport protons to protonate QB. Furthermore, isothermal titration calorimetry experiments showed a diminished 3-(3,4-dichlorophenyl)-1, 1-dimethylurea (DCMU) binding affinity of the mutated PSII, which may be explained by a structural rotation of D1-F255 in the mutant based on structural analysis of DCMU-bound PSII. These findings offer valuable insights into the functions of D1-S264 in QB protonation and function, as well as in the DCMU-binding. en-copyright= kn-copyright= en-aut-name=FanSongbo en-aut-sei=Fan en-aut-mei=Songbo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=JiangHaowei en-aut-sei=Jiang en-aut-mei=Haowei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsaiPi-Cheng en-aut-sei=Tsai en-aut-mei=Pi-Cheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JiaAnqi en-aut-sei=Jia en-aut-mei=Anqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugiuraMiwa en-aut-sei=Sugiura en-aut-mei=Miwa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Proteo-Science Research Center, Ehime University kn-affil= affil-num=8 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Photosystem II kn-keyword=Photosystem II en-keyword=PsbA3-S264V kn-keyword=PsbA3-S264V en-keyword=QB protonation kn-keyword=QB protonation en-keyword=DCMU-binding kn-keyword=DCMU-binding en-keyword=Thermosynechococcus elongatus kn-keyword=Thermosynechococcus elongatus END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=4 article-no= start-page=e70206 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Varicocelectomy Restores Spermatogenesis in Fontan‐Associated Varicocele: A Two‐Case Series en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Fontan circulation may cause chronic venous hypertension and predispose patients to varicocele and infertility,but the clinical significance of surgical treatment remains unclear.
Case Presentation: We describe two patients with Fontan circulation who developed Fontan-associated varicocele (FAVC). A42-year-old man presented with secondary infertility, bilateral varicocele, and progression to azoospermia after Fontan surgery.A 28-year-old man had asthenozoospermia, bilateral varicocele, and repeated failure of assisted reproductive technology. Bothunderwent bilateral microsurgical varicocelectomy with perioperative heparin bridging. Postoperative semen parameters im-proved in both patients, with sperm reappearing in the first case.
Conclusion: Varicocelectomy for FAVC may restore spermatogenesis in selected cases, but the risk of postoperative recurrencemay be increased. en-copyright= kn-copyright= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiTomoko en-aut-sei=Kobayashi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoYuko en-aut-sei=Matsumoto en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriwakeTakatoshi en-aut-sei=Moriwake en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OzakiNariaki en-aut-sei=Ozaki en-aut-mei=Nariaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Fontan circulation kn-keyword=Fontan circulation en-keyword=male infertility kn-keyword=male infertility en-keyword=spermatogenesis kn-keyword=spermatogenesis en-keyword=varicocele kn-keyword=varicocele en-keyword=varicocelectomy kn-keyword=varicocelectomy END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= 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=Clinical outcomes of near-infrared photoimmunotherapy according to immune checkpoint inhibitor timing and treatment sequence: a multicenter retrospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Near-infrared photoimmunotherapy (NIR-PIT) is a novel local treatment for recurrent or metastatic head and neck cancer. However, the clinical significance of immune checkpoint inhibitor (ICI) timing and treatment sequencing remains unclear. This study investigated their association with clinical outcomes after NIR-PIT.
Methods This multicenter retrospective study included 44 patients with 48 lesions who underwent initial NIR-PIT between January 2021 and March 2026. The primary analysis compared outcomes according to prior ICI exposure. An exploratory analysis evaluated outcomes according to treatment sequence and timing of ICI administration. The primary endpoint was local control. Secondary endpoints were objective response rate and disease control rate, while overall survival was assessed exploratorily.
Results Median local control duration was 253 days, but was 174 days in the prior ICI exposure group and 342 days in the non-prior ICI exposure group (log-rank P = 0.031). Local progression occurred in 69.2–37.1% of lesions, respectively (P = 0.059). Among 45 evaluable lesions, the objective response rate and disease control rate were 60.0–93.3%, respectively. Median overall survival was 866 days. Exploratory analyses suggested potential differences in clinical outcomes according to treatment sequence and ICI timing.
Conclusions Prior ICI exposure was associated with poorer local control after NIR-PIT. Exploratory analyses suggested that ICI timing and treatment sequencing may influence clinical outcomes. Treatment sequencing may represent an important consideration when integrating NIR-PIT and ICIs for recurrent or metastatic head and neck cancer. 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=FujimotoShohei en-aut-sei=Fujimoto en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OritaYorihisa en-aut-sei=Orita en-aut-mei=Yorihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TachibanaTomoyasu en-aut-sei=Tachibana en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kumamoto University kn-affil= affil-num=4 en-affil=Department of Otolaryngology Head and Neck Surgery, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=5 en-affil=Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Near-infrared photoimmunotherapy kn-keyword=Near-infrared photoimmunotherapy en-keyword=Immune checkpoint inhibitor kn-keyword=Immune checkpoint inhibitor en-keyword=Head and neck cancer kn-keyword=Head and neck cancer en-keyword=Treatment sequence kn-keyword=Treatment sequence en-keyword=Local control kn-keyword=Local control END start-ver=1.4 cd-journal=joma no-vol=49 cd-vols= no-issue=6 article-no= start-page=983 end-page=988 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260620 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of Deuterated Drugs on Safety: Insights from Pharmacovigilance Data Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Tetrabenazine (TBZ), a vesicular monoamine transporter 2 inhibitor, is commonly used to manage chorea; however, it may exhibit fluctuating plasma levels and elicit frequent adverse events. In this study, we aimed to clarify the effects of TBZ deuteration on its safety profile. We compared the safety profiles of TBZ and deutetrabenazine (DTBZ) in real-world clinical practice using disproportionality analysis and the large-scale pharmacovigilance database, VigiBase—the WHO’s global database of adverse drug reactions. Adverse event signals were assessed using the information component (IC). Seriousness was classified according to clinical outcome, and time to onset (TTO) was analyzed for selected events. TBZ showed signals for disorientation, dystonia, and sleep disorders (IC025 > 0), whereas DTBZ did not. Serious adverse events were reported in 54.7% of TBZ cases and 37.9% of DTBZ cases. The TTO of sleep disorder was also evaluated; however, the number of cases with available TTO information was limited. DTBZ showed fewer adverse event signals and a lower proportion of serious adverse events than TBZ. These findings suggest potential differences in the safety profiles of the two drugs, which may influence tolerability in the treatment of HD. en-copyright= kn-copyright= en-aut-name=KitagawaKohei en-aut-sei=Kitagawa en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NawaHideki en-aut-sei=Nawa en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsaiShota en-aut-sei=Asai en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwataNaohiro en-aut-sei=Iwata en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NiimuraTakahiro en-aut-sei=Niimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GodaMitsuhiro en-aut-sei=Goda en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshizawaKeisuke en-aut-sei=Ishizawa en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama Psychiatric Medical Center kn-affil= affil-num=2 en-affil=Department of Pharmacy, Faculty of Pharmacy, Shujitsu University kn-affil= affil-num=3 en-affil=Department of Pharmacy, Faculty of Pharmacy, Shujitsu University kn-affil= affil-num=4 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=6 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=8 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences kn-affil= en-keyword=deuterated drug kn-keyword=deuterated drug en-keyword=VigiBase kn-keyword=VigiBase en-keyword=heavy drug kn-keyword=heavy drug en-keyword=safety advantage kn-keyword=safety advantage en-keyword=pharmacovigilance analysis kn-keyword=pharmacovigilance analysis END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=cr.26-0206 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Single-Incision Laparoscopic Hartmann’s Reversal Using the Stoma Site in a Patient with Perioperative Anaphylaxis en-subtitle= kn-subtitle= en-abstract= kn-abstract=INTRODUCTION: Reversal of Hartmann’s procedure is associated with substantial morbidity, and further reduction of surgical invasiveness may be beneficial in selected patients. Perioperative anaphylaxis caused by anesthetic agents or skin antiseptics poses a significant challenge to surgical management. We report a case of stoma-site single-incision laparoscopic Hartmann’s reversal (HR) performed in a patient with severe perioperative allergies.
CASE PRESENTATION: A 73-year-old woman underwent an emergency open Hartmann’s procedure with partial cystectomy for perforated sigmoid colon cancer with bladder invasion. After adjuvant chemotherapy, she developed a progressively enlarging giant parastomal hernia that significantly impaired daily activities. Two attempts at HR were aborted because of perioperative anaphylactic shock. Subsequent allergy evaluations suggested rocuronium and chlorhexidine as causative agents, and povidone-iodine was also avoided based on clinical history. Approximately 14 months after the initial surgery, single-incision laparoscopic HR using the stoma site was successfully performed under general anesthesia without neuromuscular blocking agents. Preoperative skin antisepsis was performed using benzalkonium chloride, avoiding both chlorhexidine and povidone-iodine. No additional abdominal incisions were required. The operative time was 2 h 56 min, with minimal blood loss. The postoperative course was uneventful and she was discharged on POD 9.
CONCLUSIONS: Stoma-site single-incision laparoscopic HR may represent a useful surgical option for selected patients with severe perioperative allergies to anesthetic agents and skin antiseptics, in whom minimizing abdominal approach and wound-related risks is particularly important. en-copyright= kn-copyright= en-aut-name=YanagiharaTsubasa en-aut-sei=Yanagihara en-aut-mei=Tsubasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaYusuke en-aut-sei=Yoshida en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KondoYoshitaka en-aut-sei=Kondo en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama, Japan kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Hartmann’s reversal kn-keyword=Hartmann’s reversal en-keyword=single-incision laparoscopic surgery kn-keyword=single-incision laparoscopic surgery en-keyword=parastomal hernia kn-keyword=parastomal hernia en-keyword=perioperative anaphylaxis kn-keyword=perioperative anaphylaxis en-keyword=chlorhexidine allergy kn-keyword=chlorhexidine allergy END start-ver=1.4 cd-journal=joma no-vol= 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=12 cd-vols= no-issue=1 article-no= start-page=cr.26-0502 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful Lung Transplantation after Plasma Exchange in a Patient with High Thermal Amplitude Cold Agglutinins: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=INTRODUCTION: Cold agglutinins (CAs) are immunoglobulin M autoantibodies that induce red blood cell agglutination at low temperatures and may cause hemolytic or thrombotic complications during procedures associated with hypothermia. In lung transplantation (LT), blood may be exposed to low temperatures within the reperfused lung graft and the extracorporeal circulation circuit, potentially increasing the risk of CA-mediated complications. However, the perioperative significance of CAs in this setting remains unclear, and optimal management has not been established. We report a case of successful bilateral LT in a patient with high-thermal-amplitude CAs managed with preoperative plasma exchange (PLEX) and strict intraoperative temperature control.
CASE PRESENTATION: A 55-year-old man with diffuse panbronchiolitis and secondary pulmonary hypertension was listed for bilateral LT. Preoperative testing incidentally revealed clinically significant CAs, with a titer of 1:128 at 4°C and a thermal amplitude of 30°C. Because intraoperative blood temperature might approach this threshold despite active warming, a single preoperative session of PLEX using 36 units of fresh frozen plasma was performed to reduce the risk of a CA-mediated complication. Bilateral LT was subsequently completed under meticulous temperature management, including extracorporeal circulation maintained at 37.5°C, continuous systematic warming, avoidance of topical ice application, and rewarming of the donor lungs before reperfusion. After surgery, the CA titer decreased to 1:32. The postoperative course was uneventful, without thromboembolic events, primary graft dysfunction, or bronchial complications.
CONCLUSIONS: LT may be performed safely in selected patients with high-thermal-amplitude CAs when careful perioperative temperature control is combined with preoperative PLEX. PLEX should be considered when the anticipated intraoperative temperature is expected to approach the patient’s thermal amplitude threshold. en-copyright= kn-copyright= en-aut-name=MiyoshiYuya en-aut-sei=Miyoshi en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsanoNaomi en-aut-sei=Asano en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoHaruchika en-aut-sei=Yamamoto en-aut-mei=Haruchika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkaharaShuji en-aut-sei=Okahara en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Transfusion and Cell Therapy, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery, Okayama University Hospital, Okayama, Okayama, Japan kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Division of Transfusion and Cell Therapy, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=cold agglutinins kn-keyword=cold agglutinins en-keyword=thermal amplitude kn-keyword=thermal amplitude en-keyword= lung transplantation kn-keyword= lung transplantation en-keyword=plasma exchange kn-keyword=plasma exchange en-keyword=extracorporeal circulation kn-keyword=extracorporeal circulation en-keyword=perioperative management kn-keyword=perioperative management END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=3 article-no= start-page=e0910 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260226 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hepatocellular carcinoma in Fontan-associated liver disease: Incidence, risk stratification, and surveillance implications en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Hepatocellular carcinoma (HCC) is a serious complication of Fontan-associated liver disease (FALD). However, data on its incidence, risk factors, and outcomes in this rare population are limited. We aimed to assess the incidence and predictors of HCC and evaluate the utility of surveillance in patients with FALD.
Methods: We conducted a retrospective cohort study on patients with FALD who were referred to our gastroenterology department. The cumulative incidence of HCC after FALD diagnosis was calculated, and multivariate analysis was used to identify independent risk factors. Overall survival after FALD diagnosis was compared between patients who developed HCC and those who did not.
Results: A total of 120 patients with FALD were followed up for a median period of 50.0 months. The cumulative incidence rates of HCC at 1, 2, and 3 years after FALD diagnosis were 0.9%, 2.7%, and 3.9%, respectively. Elevated alpha-fetoprotein (AFP) at FALD diagnosis was independently associated with HCC development (hazard ratio, 1.29; 95% confidence interval, 1.04–1.60; p=0.01). There was no significant difference in overall survival between patients with and without HCC in this cohort (log-rank test, p=0.50).
Conclusions: Patients with FALD face a non-negligible risk of developing HCC, thus supporting the need for surveillance. Elevated AFP levels at the time of FALD diagnosis may aid in risk stratification, which enables the targeted monitoring and early detection of HCC. Furthermore, routine surveillance contributes to the excellent prognosis of patients with FALD who develop HCC, thus making their prognosis comparable to that of patients without HCC. en-copyright= kn-copyright= en-aut-name=OnishiHideki en-aut-sei=Onishi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TohNorihisa en-aut-sei=Toh en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BabaKenji en-aut-sei=Baba en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KotaniYasuhiro en-aut-sei=Kotani en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KasaharaShingo en-aut-sei=Kasahara en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Medical Development Field, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Medical Development Field, Okayama University, Okayama, Japan kn-affil= affil-num=3 en-affil=Department of Pediatric Cardiology, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Surgery, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Surgery, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=alpha-fetoprotein kn-keyword=alpha-fetoprotein en-keyword=FALD kn-keyword=FALD en-keyword=Fontan procedure kn-keyword=Fontan procedure en-keyword=retrospective cohort study kn-keyword=retrospective cohort study en-keyword=risk stratification kn-keyword=risk stratification END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=e70160 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical and Microbiological Characteristics of Invasive Group A Streptococcus Infection: Four Case Series of Re‐Emerging Pathogens en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Group A Streptococcus (GAS), particularly the M1UK lineage, has re-emerged as a major global public health concern following the COVID-19 pandemic, with a rise in invasive GAS (iGAS) and streptococcal toxic shock syndrome (STSS). Although STSS is under national surveillance in Japan, comprehensive molecular monitoring of iGAS infections remains limited, and the clinical characteristics of M1UK-associated iGAS have not been fully elucidated.
Methods: We retrospectively reviewed four consecutive iGAS cases requiring intensive care between March and May 2024. Detailed clinical, microbiological, and genomic investigations were performed to characterize the causative strains and their associated virulence profiles.
Results: All patients required respiratory and/or circulatory support with surgical debridement. Three cases involved necrotizing fasciitis, and one involved intra-abdominal infection secondary to ovarian tumor rupture. All four patients received penicillin G and clindamycin as definitive antimicrobial therapy, with two developing severe drug-related adverse events. Genotypic analysis identified three isolates as emm1 strains, including two M1UK lineage strains. The two M1UK isolates commonly harbored multiple superantigen genes. All isolates remained susceptible to β-lactam, clindamycin, and macrolide antibiotics.
Conclusion: This case series documents the identification of the M1UK lineage among critically ill patients with iGAS infections in Japan. Our findings support the need for continued molecular surveillance while reinforcing the importance of prompt surgical source control and appropriate antimicrobial therapy in the management of severe iGAS. en-copyright= kn-copyright= en-aut-name=OkaharaShuji en-aut-sei=Okahara en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamaguchiYuto en-aut-sei=Hamaguchi en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HishiikeMasanobu en-aut-sei=Hishiike en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MotoiYohei en-aut-sei=Motoi en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Intensive Care, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=7 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=emm type kn-keyword=emm type en-keyword=Group A Streptococcus kn-keyword=Group A Streptococcus en-keyword=M1UK strain kn-keyword=M1UK strain en-keyword=necrotizing fasciitis kn-keyword=necrotizing fasciitis en-keyword=Streptococcus pyogenes kn-keyword=Streptococcus pyogenes END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=26394 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cold SiO2-rich slabs reaching the CMB revealed by the seifertite phase boundary en-subtitle= kn-subtitle= en-abstract= kn-abstract=A cold silica (SiO2)-rich subducted slab creates notable heterogeneity above the core-mantle boundary (CMB), influencing the evolution of the Earth’s mantle. This slab may exhibit characteristic anomalies in the longitudinal and shear wave seismic velocity above the CMB, attributed to the SiO2 phase transition into its dense polymorph, seifertite. However, the transition depth remains unclear due to the often-observed metastable phases in experiments. To address this long-standing challenge, we conducted laser-heated diamond anvil cell experiments with synchronised rapid X-ray diffraction measurements alongside theoretical calculations. The slope of the seifertite phase boundary was less steep than previously estimated, and consequently, the temperature profile of the slab crosses the boundary twice, like the post-perovskite transition. We observed a decrease in shear wave velocity beneath Hawaii and Central America, and we found anti-correlation in seismic wave velocities matching the depth range of the seifertite transition in a cold slab beneath Central America. This may provide evidence that a cold SiO2-rich slab descends towards the CMB. en-copyright= kn-copyright= en-aut-name=SinmyoRyosuke en-aut-sei=Sinmyo en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Kawaguchi-ImadaSaori en-aut-sei=Kawaguchi-Imada en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoRei en-aut-sei=Sato en-aut-mei=Rei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtsuruKeisuke en-aut-sei=Otsuru en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawaiKenji en-aut-sei=Kawai en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakumaHiroshi en-aut-sei=Sakuma en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SueharaShigeru en-aut-sei=Suehara en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaitaniShuhou en-aut-sei=Maitani en-aut-mei=Shuhou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Physics, School of Science and Technology, Meiji University kn-affil= affil-num=2 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=3 en-affil=Department of Earth and Planetary Science, School of Science, The University of Tokyo kn-affil= affil-num=4 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=5 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=6 en-affil=Environmental Circulation Composite Materials Group, National Institute for Materials Science kn-affil= affil-num=7 en-affil=Environmental Circulation Composite Materials Group, National Institute for Materials Science kn-affil= affil-num=8 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=9 en-affil=Department of Physics, School of Science and Technology, Meiji University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=8 article-no= start-page=1278 end-page=1287 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=First Total Synthesis and Structural Elucidation of Microcystbiopterin C, a Pterin Glycoside From a Microcystis Bloom en-subtitle= kn-subtitle= en-abstract= kn-abstract=The first total synthesis and unambiguous structural elucidation of microcystbiopterin C, a pterin glycoside isolated from a Microcystis bloom, has been achieved. Two candidate biopterin glycosides (5a and 5b) corresponding to the proposed structures of microcystbiopterin C were synthesized by glycosylation of a suitably protected biopterin derivative 10 with 2,4-di-O-benzoyl-6-deoxy-3-O-methyl-α-L-mannopyranosyl bromide (9) and the corresponding α-D-mannopyranosyl bromide (22), respectively, followed by stepwise deprotection. Detailed comparison of the NMR data and the specific rotation of compounds 5a and 5b with those of the natural product established that microcystbiopterin C possesses the structure of 2′-O-(6-deoxy-3-O-methyl-α-D-mannopyranosyl)biopterin (5b). en-copyright= kn-copyright= en-aut-name=HanayaTadashi en-aut-sei=Hanaya en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwasakiKatsuya en-aut-sei=Iwasaki en-aut-mei=Katsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= en-keyword=glycosylation kn-keyword=glycosylation en-keyword=microcystbiopterin C kn-keyword=microcystbiopterin C en-keyword=pteridine kn-keyword=pteridine en-keyword=pterin glycoside kn-keyword=pterin glycoside en-keyword=structural elucidation kn-keyword=structural elucidation END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=5 article-no= start-page=1093 end-page=1101 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260624 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Breast ultrasound screening in young adult women undergoing infertility treatment at an infertility clinic: a retrospective observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Young adult women are increasingly undergoing infertility treatment; however, evidence regarding breast cancer screening in this population remains limited. Given that most women in this age group have dense breast tissue, for which mammography has limited sensitivity, breast ultrasound (US) is often used as a screening modality. A diagnosis of breast cancer during infertility treatment may affect both oncologic management and reproductive planning. This study aimed to examine the clinical relevance of breast US in women in their 30s undergoing infertility treatment at an infertility clinic.
Methods We retrospectively analyzed 1,336 women aged 30–39 years who underwent screening breast US between November 1, 2018, and June 30, 2025. Analyses were performed on a per-woman basis, including only the first screening examination for each participant. Breast composition was categorized according to the BI-RADS 5th edition Atlas. Screening outcomes—including recall rate, positive predictive value (PPV), cancer detection rate, and US findings (mass and non-mass findings)—were assessed using medical records. The continuation of infertility treatment, defined as ongoing or resumed treatment during the diagnostic evaluation period, was descriptively evaluated as part of the clinical context.
Results Of the 1,336 women, 1,277 (95.6%) were classified as having dense breasts. A total of 140 (10.5%) women were recalled for further evaluation. In these recalled cases, 147 findings were identified, comprising 113 mass lesions (76.8%) and 34 non-mass findings (23.1%). Four breast cancers were identified, corresponding to a cancer detection rate of 0.30% and a PPV of 2.86%. Histological diagnoses included one mucinous carcinoma, two invasive carcinomas of no special type (NST), and one ductal carcinoma in situ (DCIS). Following diagnostic evaluation, 124 recalled women (88.6%) continued infertility treatment.
Conclusions Breast US screening in women in their 30s undergoing infertility treatment provides descriptive findings within a specific clinical setting. The observed cancer detection rate appears to be within the range reported in previous studies; however, direct comparisons are limited due to differences in study populations and clinical contexts. The clinical course following recall was described as part of the screening pathway. Further prospective and multicenter studies are required to clarify the clinical significance of breast US screening in this population. en-copyright= kn-copyright= en-aut-name=NakanoKanako en-aut-sei=Nakano en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiYuko en-aut-sei=Takahashi en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaedaReina en-aut-sei=Maeda en-aut-mei=Reina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SajiMarie en-aut-sei=Saji en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HirataRei en-aut-sei=Hirata en-aut-mei=Rei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YukawaMotomi en-aut-sei=Yukawa en-aut-mei=Motomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkudaShizuka en-aut-sei=Okuda en-aut-mei=Shizuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HiranoMiyu en-aut-sei=Hirano en-aut-mei=Miyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HabaraToshihiro en-aut-sei=Habara en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HayashiNobuyoshi en-aut-sei=Hayashi en-aut-mei=Nobuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Radiology, Okayama Couple’s Clinic Women’s Health Checkup Center kn-affil= affil-num=2 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil= kn-affil= affil-num=4 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Senior Embryologist, Okayama Couple’s Clinic kn-affil= affil-num=8 en-affil=Department of Radiology, Okayama Couple’s Clinic Women’s Health Checkup Center kn-affil= affil-num=9 en-affil=Department of Radiology, Okayama Couple’s Clinic Women’s Health Checkup Center kn-affil= affil-num=10 en-affil=Department of Medical Technology, Okayama Couple’s Clinic kn-affil= affil-num=11 en-affil=Department of Reproductive Medicine, Okayama Couple’s Clinic kn-affil= affil-num=12 en-affil=Department of Reproductive Medicine, Okayama Couple’s Clinic kn-affil= en-keyword=Breast ultrasonography kn-keyword=Breast ultrasonography en-keyword=Infertility treatment kn-keyword=Infertility treatment en-keyword=Women in their 30s kn-keyword=Women in their 30s en-keyword=Breast cancer screening kn-keyword=Breast cancer screening en-keyword=Multidisciplinary care kn-keyword=Multidisciplinary care END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Angioarchitectural characterization of transdural supply in brain arteriovenous malformations: a multicenter retrospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Transdural supply (TDS) is a recognized angioarchitectural feature of brain arteriovenous malformations (bAVMs). We aimed to systematically characterize the angioarchitecture of TDS in bAVMs, focusing on whether transdural feeders terminated within the nidus or connected directly to the draining vein. TDS prevalence and its associated clinical features were also investigated.
Methods This retrospective study enrolled 521 patients (524 bAVMs) from 16 centers who underwent systematic six-vessel digital subtraction angiography. bAVMs were classified as nidus- or fistula-dominant. Angiography was evaluated with specific focus on the presence of TDS and the termination site of transdural feeders. TDS was classified as TDS-Nidus (fistulous point within the nidus) or TDS-DV (fistulous point at the draining vein wall).
Results TDS was identified in 88 bAVMs (16.8%). The fistula-dominant type was more frequent in bAVMs with TDS (P < 0.01). Among TDS cases, 25 (28.4%) demonstrated TDS-DV. Fistula-dominant morphology was the only independent predictor of TDS-DV (P < 0.01). No significant differences in complete occlusion rates or modified Rankin Scale score after treatment were observed between the TDS-Nidus and TDS-DV groups. Older age (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.02–1.06), larger nidus size (OR: 1.95; 95% CI: 1.60–2.42), occipital location (OR: 3.12; 95% CI: 1.28–7.62), eloquent area involvement (OR: 3.23; 95% CI: 1.61–6.50), and headache (OR: 2.85; 95% CI: 1.26–6.44) were independently associated with TDS.
Conclusion TDS-DV was identified in 28% of bAVMs with TDS and was strongly associated with fistula-dominant morphology. Recognition of this angioarchitectural pattern may facilitate angiographic characterization of bAVMs with TDS. en-copyright= kn-copyright= en-aut-name=KakuYasuyuki en-aut-sei=Kaku en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatowTetsu en-aut-sei=Satow en-aut-mei=Tetsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanoueShuichi en-aut-sei=Tanoue en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=OzakiTomohiko en-aut-sei=Ozaki en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsurutaWataro en-aut-sei=Tsuruta en-aut-mei=Wataro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakemotoYushin en-aut-sei=Takemoto en-aut-mei=Yushin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KringsTimo en-aut-sei=Krings en-aut-mei=Timo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KiyosueHiro en-aut-sei=Kiyosue en-aut-mei=Hiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Neurosurgery, Kumamoto University Hospital kn-affil= affil-num=2 en-affil=Department of Neurosurgery/Stroke Center, Kindai University Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Kurume University School of Medicine 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 Neurosurgery, University of Osaka Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Endovascular Neurosurgery, Toranomon Hospital kn-affil= affil-num=7 en-affil=Department of Neurosurgery, Kumamoto University Hospital kn-affil= affil-num=8 en-affil=Division of Neurointerventional Radiology, Lahey Hospital & Medical Center – Beth Israel Lahey Health, UMass Chan Medical School kn-affil= affil-num=9 en-affil=Department of Radiology, Kumamoto University, Graduate School of Medical Sciences, Kumamoto University kn-affil= en-keyword=Brain arteriovenous malformations kn-keyword=Brain arteriovenous malformations en-keyword=Transdural supply kn-keyword=Transdural supply en-keyword=Fistulous point kn-keyword=Fistulous point en-keyword=Nidus kn-keyword=Nidus en-keyword=Draining vein kn-keyword=Draining vein 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=52 cd-vols= no-issue=17 article-no= start-page=e2025GL115385 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phase Relations in the MgSiO3 System Associated With Hot Mantle Upwelling Across the 660 km Depth en-subtitle= kn-subtitle= en-abstract= kn-abstract=The phase transformations of MgSiO3 bridgmanite control the structure, dynamics and chemistry of the Earth's mantle. Formation of bridgmanite occurs at a depth of about 660 km causing the strong and abrupt seismic discontinuity. Previous experimental studies have revealed that this discontinuity is caused by ringwoodite dissociation in the average mantle. However, the cause of the 660-km seismic discontinuity beneath hotspots remains unclear. Here we determine the phase relations in the MgSiO3 system near the 660-km seismic discontinuity conditions. At 2,200–2,350 K with decreasing pressure, MgSiO3 bridgmanite first transforms to akimotoite and then to garnet. The akimotoite-bridgmanite boundary has almost no temperature dependence, whereas the garnet–akimotoite transition has a very steep positive boundary slope. Based on these slopes, we calculated the garnet–bridgmanite boundary slope. Depending on the temperature regime, the akimotoite-bridgmanite or the garnet–bridgmanite transition may occur in ascending plume beneath hotspots near the 660 km depth. en-copyright= kn-copyright= en-aut-name=ChanyshevArtem en-aut-sei=Chanyshev en-aut-mei=Artem kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PurevjavNarangoo en-aut-sei=Purevjav en-aut-mei=Narangoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BondarDmitry en-aut-sei=Bondar en-aut-mei=Dmitry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TangHu en-aut-sei=Tang en-aut-mei=Hu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FeiHongzhan en-aut-sei=Fei en-aut-mei=Hongzhan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WangLin en-aut-sei=Wang en-aut-mei=Lin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WangFei en-aut-sei=Wang en-aut-mei=Fei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KimEun Jeong en-aut-sei=Kim en-aut-mei=Eun Jeong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=LiuDan en-aut-sei=Liu en-aut-mei=Dan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=BhatShrikant en-aut-sei=Bhat en-aut-mei=Shrikant kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FarlaRobert en-aut-sei=Farla en-aut-mei=Robert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KatsuraTomoo en-aut-sei=Katsura en-aut-mei=Tomoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=2 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=3 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=4 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=5 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=6 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=7 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=8 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=9 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=10 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=11 en-affil=Deutsches Elektronen‐Synchrotron DESY kn-affil= affil-num=12 en-affil=Deutsches Elektronen‐Synchrotron DESY kn-affil= affil-num=13 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= en-keyword=experimental kn-keyword=experimental en-keyword=high-pressure kn-keyword=high-pressure en-keyword=in situ X-ray diffraction kn-keyword=in situ X-ray diffraction en-keyword=bridgmanite kn-keyword=bridgmanite en-keyword=geodynamics kn-keyword=geodynamics en-keyword=phase relations kn-keyword=phase relations END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=9 article-no= start-page=5141 end-page=5154 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=Antiproteinuric Effect of SGLT2 Inhibitors in Patients With Hepatocellular Carcinoma Receiving Atezolizumab Plus Bevacizumab en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce proteinuria in patients with diabetes mellitus and chronic kidney disease. However, their effect on vascular endothelial growth factor inhibitor-induced proteinuria remains unclear. This study evaluated the prophylactic effect of SGLT2i on bevacizumab-induced proteinuria in patients with hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab.
Patients and Methods: This multicenter retrospective study included patients with HCC who started therapy with atezolizumab plus bevacizumab between September 2020 and December 2023. The primary outcome was the time to exacerbation of proteinuria from baseline within 6 months after treatment initiation according to SGLT2i use. Secondary outcomes included the development of grade ≥2 proteinuria.
Results: A total of 188 patients were included, of whom 29 received SGLT2i. No significant difference in the time to exacerbation of proteinuria was observed between the SGLT2i and non-SGLT2i groups considering the overall population (median: 157 vs. 116 days, p=0.95). Multivariate analysis identified diabetes with systolic blood pressure ≥130 mmHg as an independent risk factor for proteinuria exacerbation (hazard ratio=2.19, 95% confidence interval=1.18-4.06, p=0.013), whereas SGLT2i use was not significantly associated with proteinuria exacerbation. In patients with both diabetes and systolic blood pressure ≥130 mmHg, SGLT2i significantly prolonged the time to proteinuria exacerbation.
Conclusion: SGLT2i may suppress proteinuria progression only in high-risk patients with HCC complicated by diabetes and hypertension. en-copyright= kn-copyright= en-aut-name=HORITOMOKI en-aut-sei=HORI en-aut-mei=TOMOKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YAMAMOTOKAZUHIRO en-aut-sei=YAMAMOTO en-aut-mei=KAZUHIRO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AOIHIROSHI en-aut-sei=AOI en-aut-mei=HIROSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KOIZUMIYUSUKE en-aut-sei=KOIZUMI en-aut-mei=YUSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KUROMATSUMAKOTO en-aut-sei=KUROMATSU en-aut-mei=MAKOTO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FUKUIAIKO en-aut-sei=FUKUI en-aut-mei=AIKO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OKAMOTOHIROYO en-aut-sei=OKAMOTO en-aut-mei=HIROYO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HIRATAATSUSHI en-aut-sei=HIRATA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SHINMORIKENTARO en-aut-sei=SHINMORI en-aut-mei=KENTARO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IMANAKAYUKI en-aut-sei=IMANAKA en-aut-mei=YUKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NAMBAMIYU en-aut-sei=NAMBA en-aut-mei=MIYU kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KITAMURASYUNSUKE en-aut-sei=KITAMURA en-aut-mei=SYUNSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NAKANISHIKEISUKE en-aut-sei=NAKANISHI en-aut-mei=KEISUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TSUSHIMAHIDEO en-aut-sei=TSUSHIMA en-aut-mei=HIDEO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= en-aut-name=MORIYAKEI en-aut-sei=MORIYA en-aut-mei=KEI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MATSUIMASARU en-aut-sei=MATSUI en-aut-mei=MASARU kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IKUSHIMASHIGEKI en-aut-sei=IKUSHIMA en-aut-mei=SHIGEKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=2 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacy, Nara Medical University Hospital kn-affil= affil-num=4 en-affil=Department of Pharmacy, Nara Medical University Hospital kn-affil= affil-num=5 en-affil=Department of Pharmacy, Tenri Hospital kn-affil= affil-num=6 en-affil=Department of Pharmacy, Kindai University Nara Hospital kn-affil= affil-num=7 en-affil=Department of Pharmacy, Kindai University Nara Hospital kn-affil= affil-num=8 en-affil=Department of Pharmacy, Kindai University Nara Hospital kn-affil= affil-num=9 en-affil=Department of Pharmacy, Yamatotakada Municipal Hospital kn-affil= affil-num=10 en-affil=Department of Pharmacy, Yamatotakada Municipal Hospital kn-affil= affil-num=11 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=12 en-affil=Department of Nephrology, Nara Medical University Hospital kn-affil= affil-num=13 en-affil=Department of Gastroenterology, Nara Prefecture General Medical Center kn-affil= affil-num=14 en-affil=Department of Nephrology, Nara Prefecture General Medical Center kn-affil= affil-num=15 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=16 en-affil=Department of Gastroenterology, Nara Prefecture General Medical Center kn-affil= affil-num=17 en-affil=Department of Nephrology, Nara Medical University Hospital kn-affil= affil-num=18 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= en-keyword=Hepatocellular carcinoma kn-keyword=Hepatocellular carcinoma en-keyword=bevacizumab kn-keyword=bevacizumab en-keyword=proteinuria kn-keyword=proteinuria en-keyword=sodium glucose transporter 2 inhibitors kn-keyword=sodium glucose transporter 2 inhibitors END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=8291 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Water exchange process and bulk composition regulate slab dynamics and deep earthquakes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Water strongly influences deep mantle processes, including geochemical cycles, slab dynamics, and deep-focus earthquakes. Yet the stability and interactions of hydrous minerals with nominally anhydrous minerals (NAMs) under the water-undersaturated conditions of subducting slabs remain unclear. Here we show, using high-pressure and high-temperature experiments on MgO–SiO2–H2O systems (~2 wt% H2O), that hydrous minerals progressively dehydrate in the mantle transition zone, transferring water to NAMs such as wadsleyite and ringwoodite, while the cold slab core stays nearly dry. Rapid dehydration near the top of the lower mantle may generate fluids linked to the deepest earthquakes. Our results indicate that dry olivine transformations, rather than dehydration embrittlement, likely trigger most deep-focus earthquakes, and that hydration variations in NAMs influence slab deformation and stagnation above 660 km. The bulk Mg/Si ratio controls hydrous mineral stability, suggesting harzburgite transports water more efficiently than peridotite. en-copyright= kn-copyright= en-aut-name=ZhuJintao en-aut-sei=Zhu en-aut-mei=Jintao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TaoRenbiao en-aut-sei=Tao en-aut-mei=Renbiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZhangLifei en-aut-sei=Zhang en-aut-mei=Lifei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Center for High Pressure Science and Technology Advanced Research (HPSTAR) kn-affil= affil-num=3 en-affil=SKLab-DeepMinE, MOEKLab-OBCE, School of Earth and Space Sciences, Peking University kn-affil= affil-num=4 en-affil=Institute for Planetary Materials, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=44 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260622 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of a preoperative accuracy prediction model using machine learning for implant placement in static-guided surgery: retrospective observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose This study aimed to develop a machine learning model capable of preoperatively predicting three-dimensional implant placement errors at the implant apex in static-guided surgery and to identify the clinical features associated with placement accuracy.
Methods Clinical data partially derived from a previous observational study were analyzed. In total, 181 patients and 480 implants placed using fully static-guided surgery were included in this study. The outcome variable was defined as three-dimensional implant placement error at the implant apex relative to the preoperative simulation, dichotomized as less than 0.5 mm or ≥ 0.5 mm. Twenty-one clinical and radiographic factors previously suggested to influence the placement accuracy were used as explanatory variables. The feature importance was evaluated using three gradient boosting decision tree models. Furthermore, a stacking model combining multiple classifiers was constructed, and the classification performance was assessed using ten-fold cross-validation.
Results The feature importance analysis identified 12 features associated with implant placement errors. The stacking model demonstrated superior classification performance compared to individual classifiers. The true positive rate was 0.73, false negative rate was 0.27, false positive rate was 0.14, and true negative rate was 0.86.
Conclusions The proposed stacking model correctly classified 86% of cases with implant placement error less than 0.5 mm and 73% of cases with implant placement error of ≥ 0.5 mm. These findings suggest that the proposed model may support the preoperative evaluation of implant placement accuracy in static-guided surgeries. en-copyright= kn-copyright= en-aut-name=MinoTakuya en-aut-sei=Mino en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuokaYurina en-aut-sei=Matsuoka en-aut-mei=Yurina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorookaKen’ichi en-aut-sei=Morooka en-aut-mei=Ken’ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TokumotoKana en-aut-sei=Tokumoto en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimizuHiroaki en-aut-sei=Shimizu en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurosakiYoko en-aut-sei=Kurosaki en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Kimura-OnoAya en-aut-sei=Kimura-Ono en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KishimotoHiromitsu en-aut-sei=Kishimoto en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KubokiTakuo en-aut-sei=Kuboki en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MaekawaKenji en-aut-sei=Maekawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University kn-affil= affil-num=2 en-affil=Department of Semiconductor, Computer Science and Applied Mathematics, Graduate School of Science and Technology, Kumamoto University kn-affil= affil-num=3 en-affil=Division of Biomedical Engineering, Faculty of Advanced Science and Technology, Kumamoto University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, School of Medicine, Hyogo Medical University kn-affil= affil-num=5 en-affil=Shimizu Dental Clinic kn-affil= affil-num=6 en-affil=Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University kn-affil= affil-num=7 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, School of Medicine, Hyogo Medical University kn-affil= affil-num=9 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University kn-affil= en-keyword=Implant placement kn-keyword=Implant placement en-keyword=Accuracy kn-keyword=Accuracy en-keyword=Surgical guide kn-keyword=Surgical guide en-keyword=Machine learning kn-keyword=Machine learning en-keyword=Prediction algorithms kn-keyword=Prediction algorithms en-keyword=Decision trees kn-keyword=Decision trees en-keyword=Support vector machine kn-keyword=Support vector machine en-keyword=Sensitivity and specificity kn-keyword=Sensitivity and specificity END start-ver=1.4 cd-journal=joma no-vol=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=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 < 0.001).
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=32 cd-vols= no-issue=7 article-no= start-page=103553 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Patient-centred communication in radiographer education: A five-country comparative document analysis of curriculum and competency standards en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Patient-centred communication is fundamental to radiographic practice, particularly when patients experience anxiety or uncertainty during imaging or treatment. However, it remains unclear whether broad communication expectations in radiography education and professional standards are translated into explicit, observable behaviours and integrated into education and assessment. This comparative document analysis examined the representation of patient-centred communication in selected national-level documents from five countries, using listening-related behaviours as an illustrative example.
Methods: Selected national-level curriculum, accreditation, registration, capability, and competency documents from the United States, the United Kingdom, Australia, Canada, and Japan were analysed deductively using a predefined extraction framework. The framework assessed communication competence, listening-related behaviours, patient-centred care, patient/family relationships, interprofessional collaboration, education, and assessment.
Results: Communication was addressed in all five selected national-level document sets, although institutional framing differed. It was framed as a professional competency or capability in the United Kingdom and Australia, a role-based competency framework in Canada, clinical competency and accreditation requirements in the United States, and primarily as curriculum content in Japan. Explicit observable behavioural expectations, such as listening-related behaviours, were uncommon. Listening was explicitly defined only in the Australian capability standards; elsewhere, it was represented indirectly through broader concepts, such as patient interaction, information gathering, and interpersonal communication.
Conclusion: The selected documents differed in the explicitness, structure, and educational integration of communication-related standards, without implying differences in education quality or clinical outcomes. Defining patient-centred communication through observable behaviours may strengthen alignment among professional expectations, learning outcomes, feedback, and assessment.
Implications for practice: Operationalising patient-centred communication as observable behaviours may enhance curriculum mapping, feedback, and assessment in radiographer education. en-copyright= kn-copyright= en-aut-name=KomatsuY. en-aut-sei=Komatsu en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChikamotoY. en-aut-sei=Chikamoto en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsukanoK. en-aut-sei=Tsukano en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeS. en-aut-sei=Abe en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsudouS. en-aut-sei=Tsudou en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoY. en-aut-sei=Yamamoto en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanabeY. en-aut-sei=Tanabe en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Division of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Independent Researcher kn-affil= affil-num=3 en-affil=Department of Psychosomatic Medicine, Yokohama Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Radiological Technology, Faculty of Health Care Sciences, Jikei University of Health Care Sciences kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Faculty of Health Care Sciences, Jikei University of Health Care Sciences kn-affil= affil-num=6 en-affil=Division of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Division of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=Radiographer education kn-keyword=Radiographer education en-keyword=Patient-centred communication kn-keyword=Patient-centred communication en-keyword=Listening kn-keyword=Listening en-keyword=Competency standards kn-keyword=Competency standards en-keyword=Curriculum standards kn-keyword=Curriculum standards en-keyword=Document analysis kn-keyword=Document analysis END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue=10 article-no= start-page=107906 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical characteristics and therapeutic dilemmas in nocardiosis: Insights from a case series en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Nocardiosis often requires prolonged antimicrobial therapy, and trimethoprim–sulfamethoxazole (TMP–SMX) is considered the cornerstone of treatment. However, TMP–SMX–related adverse events frequently complicate long-term therapy, and real-world data regarding treatment continuity and outcomes remain limited. Methods: We conducted a retrospective observational study of patients with Nocardia species isolated from clinical specimens at a tertiary-care academic hospital in Japan between January 2015 and April 2025. Clinical characteristics, antimicrobial therapy, adverse events, and outcomes were reviewed.
Results: Eleven cases were enrolled, with a median age of 65 years. The cohort comprised seven patients with severe nocardiosis (disseminated disease, brain abscess, and pneumonia in transplant recipients) and four patients with mild nocardiosis (cutaneous infection and pneumonia). Nine patients received TMP–SMX as part of the initial regimen, of whom seven required modification of therapy within 1 day to 3 months because of adverse events. Following modification of TMP–SMX, patients were treated with alternative regimens, including fluoroquinolone—and minocycline-based therapies, as well as β-lactam–containing combinations. Importantly, no cases of treatment failure or death were observed, and no relapses were identified during the available follow-up period, even among patients with those clinically complex diseases.
Conclusions: Although TMP–SMX is the first-line therapy for nocardiosis, the majority of our patients did not tolerate the drug. Nevertheless, favorable outcomes were observed with alternative regimens, even in patients with clinically complex disease, suggesting that alternative regimens may be reasonable options when TMP–SMX is not tolerated. en-copyright= kn-copyright= en-aut-name=AkazawaHidemasa en-aut-sei=Akazawa en-aut-mei=Hidemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyaharaTomoyuki en-aut-sei=Miyahara en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OgawaSakura en-aut-sei=Ogawa en-aut-mei=Sakura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=7 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Nocardiosis kn-keyword=Nocardiosis en-keyword=Treatment kn-keyword=Treatment en-keyword=Trimethoprim–sulfamethoxazole kn-keyword=Trimethoprim–sulfamethoxazole en-keyword=Alternative therapy kn-keyword=Alternative therapy en-keyword=Dose modification kn-keyword=Dose modification END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fenestration Re-creation for Early Fontan Deterioration: Long-Term Hemodynamic and Clinical Outcomes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spontaneous closure of a Fontan fenestration may precipitate early hemodynamic deterioration in vulnerable patients. In such situations, fenestration re-creation may be considered as a rescue strategy when medical therapy is insufficient. However, the long-term hemodynamic consequences of this intervention remain poorly defined. We retrospectively reviewed 62 patients who underwent the Fontan procedure between January 2011 and December 2020 and subsequently experienced spontaneous fenestration closure. Patients were divided into two groups according to management strategy: those who underwent fenestration re-creation (Group 1, n = 19) and those managed without re-creation (Group 2, n = 43). Longitudinal hemodynamic data were analyzed using linear mixed models over a median follow-up of 10.2 years. Fenestration closed spontaneously at a median of 12 days (IQR 2.5–26.5) and initial re-creation was performed at the median of 42 days (IQR 11–213) postoperatively. Early and mide-term hemodynamic trends were broadly similar between groups, however, clear divergence emerged in the late follow-up. fenestration re-created patients demonstrated persistently higher central venous pressure and pulmonary vascular resistance, lower systemic vascular resistance, progressive increases in cardiac index, and declining oxygen saturation. Survival in this group remained above 80% during the mid-term follow-up but declined substantially in the late phase compared with patients without re-creation (52% vs. 85%, p = 0.043). This was accompanied by higher incidences of protein-losing enteropathy/plastic bronchitis, thromboembolism, and severe cyanosis. Fenestration re-creation may provide temporary hemodynamic stabilization in early Fontan deterioration; however, its benefits appear to diminish in the late phase. These findings highlight the need for hemodynamically tailored management strategies and alternative therapeutic options for patients with deteriorating Fontan circulation. en-copyright= kn-copyright= en-aut-name=TranThi Hai Yen en-aut-sei=Tran en-aut-mei=Thi Hai Yen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuritaYoshihiko en-aut-sei=Kurita en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoMaiko en-aut-sei=Kondo en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukushimaYosuke en-aut-sei=Fukushima en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShigemitsuYusuke en-aut-sei=Shigemitsu en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawamotoYuya en-aut-sei=Kawamoto en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaraMayuko en-aut-sei=Hara en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwasakiTatsuo en-aut-sei=Iwasaki en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KasaharaShingo en-aut-sei=Kasahara en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=BabaKenji en-aut-sei=Baba en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Pediatrics, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatric anesthesiology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Cardiovascular Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Fontan operation kn-keyword=Fontan operation en-keyword=Spontaneous fenestration closure kn-keyword=Spontaneous fenestration closure en-keyword=Fenestration recreation kn-keyword=Fenestration recreation en-keyword=Longitudinal hemodynamic changes kn-keyword=Longitudinal hemodynamic changes END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=22258 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260711 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Microstructural changes in irradiated teeth revealed by swept-source optical coherence tomography en-subtitle= kn-subtitle= en-abstract= kn-abstract=Radiation-induced caries is a late complication of radiotherapy for head and neck cancers. Although direct irradiation-induced changes in tooth structure may contribute to its development, these changes have not been fully characterized. This study evaluated irradiation-associated microstructural alterations and tissue density changes in human teeth using swept-source optical coherence tomography (SS-OCT). Eight extracted fully impacted human third molars were assigned to irradiated and non-irradiated groups (n = 4 each). The irradiated group received X-rays at a total dose of 70 Gy, a clinically relevant dose in definitive radiotherapy for head and neck cancer. A total of 64 SS-OCT cross-sectional images were obtained and analyzed, with 32 images from each group, including 16 from the coronal area on the occlusal side and 16 from the cervical area. Microcrack-like features were observed in 100% (16/16) of irradiated and 31.3% (5/16) of non-irradiated images in the coronal area on the occlusal side, and in 43.8% (7/16) and 0% (0/16) of images in the cervical area, respectively. Attenuation coefficients were significantly higher in irradiated enamel and dentin. These findings suggest that irradiation-induced microstructural changes in extracted human teeth in vitro may contribute to increased susceptibility to radiation-induced caries. en-copyright= kn-copyright= en-aut-name=MatsuzakiKumiko en-aut-sei=Matsuzaki en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuzakiHidenobu en-aut-sei=Matsuzaki en-aut-mei=Hidenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TabataTomoko en-aut-sei=Tabata en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AoyamaHideki en-aut-sei=Aoyama en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshioKotaro en-aut-sei=Yoshio en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KosakiHirotaka en-aut-sei=Kosaki en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OharaNaoko en-aut-sei=Ohara en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SadrAlireza en-aut-sei=Sadr en-aut-mei=Alireza kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SogaYoshihiko en-aut-sei=Soga en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShimadaYasushi en-aut-sei=Shimada en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Oral Diagnosis and Dentomaxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= affil-num=4 en-affil=Central Division of Radiology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Biomimetics Biomaterials Biophotonics Biomechanics & Technology Laboratory, Department of Restorative Dentistry, Magnuson Health Sciences Center, University of Washington kn-affil= affil-num=9 en-affil=Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= en-keyword=Radiation-induced caries kn-keyword=Radiation-induced caries en-keyword=Dental enamel kn-keyword=Dental enamel en-keyword=Dentin kn-keyword=Dentin en-keyword=Radiation effects kn-keyword=Radiation effects en-keyword=Swept-source optical coherence tomography kn-keyword=Swept-source optical coherence tomography END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=6 article-no= start-page=ofag338 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=Digital Tattoos in Infectious Diseases Management en-subtitle= kn-subtitle= en-abstract= kn-abstract=The widespread adoption of electronic medical records (EMRs) has improved continuity and efficiency in healthcare; however, the permanence of digital documentation may unknowingly and unintentionally disadvantage patients. Certain infectious disease–related labels, particularly those denoting colonization of antimicrobial-resistant organisms, status of stigmatized diseases, or antibiotic drug allergy, frequently persist long after their clinical relevance has expired. These Digital Tattoos silently influence clinical decision-making and impose multifaceted burdens, leading to unnecessary isolation, excessive use of broad-spectrum antimicrobials, psychological distress, higher healthcare costs, and reinforcement of stigma. A critical mismatch exists between static (unchanged) EMRs and the dynamic (changeable) nature of clinical conditions. To mitigate the harms of Digital Tattoos, we must urgently move beyond passive documentation toward proactive management of healthcare data. Decoupling the permanence of digital records from systemic inequities in patient care hinges on the robust synthesis of Digital Humility and patient-oriented risk evaluation. en-copyright= kn-copyright= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=antibiotic allergy kn-keyword=antibiotic allergy en-keyword=antimicrobial resistance kn-keyword=antimicrobial resistance en-keyword=infectious diseases kn-keyword=infectious diseases en-keyword=isolation kn-keyword=isolation en-keyword=stigma kn-keyword=stigma END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=FM4B.2 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=Demonstration of a Raman Silicon Nanocavity Laser Emitting in the L-Band with S-band excitation en-subtitle= kn-subtitle= en-abstract= kn-abstract=We demonstrated a Raman silicon nanocavity laser that enables wavelength conversion from the S-band to the L-band. Compared with Raman lasers operating from the E-band to the C-band, a degradation in lasing threshold was observed. en-copyright= kn-copyright= en-aut-name=IchinoseRikuto en-aut-sei=Ichinose en-aut-mei=Rikuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamasakiShoei en-aut-sei=Yamasaki en-aut-mei=Shoei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshiharaAyumi en-aut-sei=Ishihara en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanemaruYuta en-aut-sei=Kanemaru en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AsanoTakashi en-aut-sei=Asano en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NodaSusumu en-aut-sei=Noda en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= affil-num=1 en-affil=Department of Physics and Electronics, Osaka Metropolitan University kn-affil= affil-num=2 en-affil=Department of Physics and Electronics, Osaka Metropolitan University kn-affil= affil-num=3 en-affil=Department of Environmental, Life, and Natural Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Physics and Electronics, Osaka Metropolitan University kn-affil= affil-num=5 en-affil=Department of Electronic Science and Engineering, Kyoto University kn-affil= affil-num=6 en-affil=Department of Electronic Science and Engineering, Kyoto University kn-affil= affil-num=7 en-affil=Department of Environmental, Life, and Natural Sciences, Okayama University kn-affil= 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=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=29 cd-vols= no-issue=8 article-no= start-page=117125 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Brain circadian clock neurons drive fitness advantages in Drosophila en-subtitle= kn-subtitle= en-abstract= kn-abstract=The adaptive significance of circadian clocks is widely assumed due to their ubiquity; yet, direct empirical evidence remains scarce. Evaluating these benefits is often confounded by pleiotropic effects in conventional circadian null mutants. To address this, we selectively altered the circadian period exclusively within brain clock neurons in Drosophila melanogaster. Multi-generational competition assays revealed that flies with aberrant rhythms exhibit a significant fitness disadvantage under standard light-dark (LD 12:12) cycles. This disadvantage was abolished under constant light, confirming that the selection pressure is specifically mediated by the circadian clock. Furthermore, paternity assays conducted under LD 12:12 indicated that the timing of brain clock neurons influences male reproductive success, providing a potential mechanistic link between clock-controlled behavior and fitness. Intriguingly, we found that these fitness costs are highly photoperiod-dependent. Under short-day conditions (LD 8:16), the short-period strain (dbtS) maintained a significantly higher overall frequency than the long-period strain (dbtL). Our behavioral observations suggest that this difference may be associated with the quality of activity rhythms; specifically, dbtS lacked defined morning peaks and showed suppressed nocturnal activity, potentially narrowing its window for reproductive interactions compared to dbtL. These findings illustrate that the circadian system does not merely track a 24-h cycle but functions as a flexible feature that enables flies to cope with changing day lengths by aligning their mating behavior with the most favorable time of day. en-copyright= kn-copyright= en-aut-name=AikawaSae en-aut-sei=Aikawa en-aut-mei=Sae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TamuraShoichiro en-aut-sei=Tamura en-aut-mei=Shoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MimuraMakiko en-aut-sei=Mimura en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshiiTaishi en-aut-sei=Yoshii en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=activity rhythms kn-keyword=activity rhythms en-keyword=clock neurons kn-keyword=clock neurons en-keyword=Drosophila kn-keyword=Drosophila en-keyword=adaptive advantage kn-keyword=adaptive advantage en-keyword=reproductive success kn-keyword=reproductive success en-keyword=resonance hypothesis kn-keyword=resonance hypothesis END start-ver=1.4 cd-journal=joma no-vol=127 cd-vols= no-issue=3 article-no= start-page=e71081 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=AHG1–AFP interaction as a regulatory node in the ABA response during seed germination en-subtitle= kn-subtitle= en-abstract= kn-abstract=Seed dormancy and germination are tightly regulated by complex signaling networks that integrate internal and external cues, including the endogenous phytohormone abscisic acid (ABA). ABA HYPERSENSITIVE GERMINATION 1 (AHG1), a group A type 2C protein phosphatase (PP2C), is thought to modulate the activity of transcription factors such as ABA INSENSITIVE 5 (ABI5) in seeds and during germination. AHG1 is regulated by DELAY OF GERMINATION 1 (DOG1), a key regulator of seed dormancy, through physical interaction. We previously reported that AHG1 also interacts with ABI FIVE BINDING PROTEIN 2 (AFP2), a member of the AFP family; however, the molecular basis of AHG1–AFP coordination has remained unclear. In this study, we show that AHG1 interacts with all AFP family members and that AFP3 binds AHG1 and ABI5 through adjacent but distinct amino acid residues within its C-domain, allowing simultaneous association with both proteins. In addition, AHG1 modulates the phosphorylation status of AFP3 at Ser60 in a DOG1-dependent manner, suggesting that DOG1–AHG1 regulates AFP3 post-translationally. Transcriptomic analyses of AHG1- or AFP3-overexpressing lines revealed that these factors are associated with the regulation of a shared set of ABA-responsive genes, including AFPs, and that AFP3 overexpression is predominantly associated with altered expression of genes involved in transcriptional regulation. Large-scale protein interaction analyses showed that AFPs interact with multiple classes of transcription factors, suggesting their involvement in diverse regulatory pathways, including ABA signaling. Together, these findings demonstrate that DOG1 regulates ABI5 function and modulates ABA responses, at least in part, by controlling AHG1-mediated dephosphorylation of AFPs. en-copyright= kn-copyright= en-aut-name=NishimuraNoriyuki en-aut-sei=Nishimura en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UshiyamaSho en-aut-sei=Ushiyama en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtagiriMasato en-aut-sei=Otagiri en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatohKouji en-aut-sei=Satoh en-aut-mei=Kouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiNahomi en-aut-sei=Suzuki en-aut-mei=Nahomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IrisaTomoko en-aut-sei=Irisa en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MitsudaNobutaka en-aut-sei=Mitsuda en-aut-mei=Nobutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UmezawaTaishi en-aut-sei=Umezawa en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishimuraHideki en-aut-sei=Nishimura en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NemotoKeiichirou en-aut-sei=Nemoto en-aut-mei=Keiichirou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsuchiyaWataru en-aut-sei=Tsuchiya en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YanoRyoichi en-aut-sei=Yano en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SawasakiTatsuya en-aut-sei=Sawasaki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamazakiToshimasa en-aut-sei=Yamazaki en-aut-mei=Toshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HirayamaTakashi en-aut-sei=Hirayama en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Institute of Agrobiological Sciences, National Agriculture and Food Research Organization kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Agrobiological Sciences, National Agriculture and Food Research Organization kn-affil= affil-num=5 en-affil=Institute of Agrobiological Sciences, National Agriculture and Food Research Organization kn-affil= affil-num=6 en-affil=Institute of Agrobiological Sciences, National Agriculture and Food Research Organization kn-affil= affil-num=7 en-affil=Biomanufacturing Process Research Center, National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=8 en-affil=Graduate School of Advanced Interdisciplinary Science, Tokyo University of Agriculture and Technology kn-affil= affil-num=9 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=10 en-affil=Proteo-Science Center, PIAS, Ehime University kn-affil= affil-num=11 en-affil=Research Center for Advanced Analysis, National Agriculture and Food Research Organization kn-affil= affil-num=12 en-affil=Research Center for Advanced Analysis, National Agriculture and Food Research Organization kn-affil= affil-num=13 en-affil=Proteo-Science Center, PIAS, Ehime University kn-affil= affil-num=14 en-affil=Research Center for Advanced Analysis National Agriculture and Food Research Organization Tsukuba Ibaraki 305‐8518 Japan kn-affil= affil-num=15 en-affil=Research Center for Advanced Analysis, National Agriculture and Food Research Organization kn-affil= en-keyword=ABA kn-keyword=ABA en-keyword=AHG1 kn-keyword=AHG1 en-keyword=AFP kn-keyword=AFP en-keyword=ABI5 kn-keyword=ABI5 en-keyword=DOG1 kn-keyword=DOG1 en-keyword=seed dormancy kn-keyword=seed dormancy en-keyword=seed germination kn-keyword=seed germination en-keyword=Arabidopsis thaliana kn-keyword=Arabidopsis thaliana END start-ver=1.4 cd-journal=joma no-vol=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=15 cd-vols= no-issue=13 article-no= start-page=4866 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260623 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Changing Trends in Cardiovascular Disease Burden in North Africa and the Middle East, 1990–2023: A Joinpoint Analysis of GBD 2023 Data en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Cardiovascular disease (CVD) burden decreased in the North Africa and Middle East (NAME) region between 1990 and 2019. This study used Global Burden of Disease (GBD) 2023 data to examine whether trends in mortality, disability-adjusted life years (DALYs), incidence, and prevalence continued through 2023 across all 21 NAME countries. Methods: We analysed age-standardised CVD mortality, incidence, prevalence, and DALY rates from 1990 to 2023. Joinpoint regression identified changes in temporal trends and calculated the annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals (CIs). Results: Age-standardised CVD mortality decreased from 579.6 per 100,000 in 1990 to 358.2 in 2023 (AAPC: −1.42%; 95% CI: −1.48 to −1.35). However, no significant reduction occurred between 2019 and 2023 (APC: −0.33%; 95% CI: −1.37 to 1.75). DALY, incidence, and prevalence rates followed similar patterns, with no significant decline in the final years of this study. Egypt was the only country with a long-term increase in CVD mortality, which accelerated after 2020 (APC: +5.20%; 95% CI: 1.20 to 12.87). High systolic blood pressure, dietary risks, lead exposure, and air pollution were the leading modifiable risk factors. Conclusions: The earlier decline in CVD burden in the NAME region did not clearly continue after 2019. The region is currently off track to meet Sustainable Development Goal 3.4 by 2030. Future progress may depend on improved blood pressure control, lipid management, dietary habits, and environmental risk reduction. en-copyright= kn-copyright= en-aut-name=OuddoudHanane en-aut-sei=Ouddoud en-aut-mei=Hanane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LescanoJudah Israel Ong en-aut-sei=Lescano en-aut-mei=Judah Israel Ong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BelangoyKeith Pardillada en-aut-sei=Belangoy en-aut-mei=Keith Pardillada kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaradaKo en-aut-sei=Harada en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=VuQuynh Thi en-aut-sei=Vu en-aut-mei=Quynh Thi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Division of Hematology and Oncology, Mayo Clinic kn-affil= affil-num=5 en-affil=Division of Hematology and Oncology, Mayo Clinic kn-affil= affil-num=6 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=cardiovascular diseases kn-keyword=cardiovascular diseases en-keyword=global burden of disease kn-keyword=global burden of disease en-keyword=North Africa and Middle East kn-keyword=North Africa and Middle East en-keyword=risk factors kn-keyword=risk factors en-keyword=joinpoint regression kn-keyword=joinpoint regression END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=13203 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Amyloid-forming property of the N-terminal 1−70 residues of human apolipoprotein A-IV en-subtitle= kn-subtitle= en-abstract= kn-abstract=Apolipoprotein A-IV (apoA-IV), the largest member of the exchangeable apolipoprotein family, is a common constituent of amyloid deposits in renal and cardiac amyloidosis. In this study, we characterized the aggregation propensity of the apoA-IV N-terminal fragment to form amyloid fibrils using a variety of biophysical techniques. Thioflavin T fluorescence assay, circular dichroism measurement, and microscopic observations revealed that the N-terminal 1−70 amino acid fragment of apoA-IV readily forms amyloid fibrils by a transition from a random coil to a β-sheet-rich structure. Sequence-based analysis indicated that residues 7−16 and 38−42 are the major aggregation-prone segments within the N-terminal 1−70 residues of apoA-IV. Consistent with this, deletion of these residues strongly inhibited the β-transition and fibril formation of apoA-IV 1−70. Kinetic and thermodynamic analyses of fibril formation by the apoA-IV 1−70 fragment demonstrated that primary nucleation is the dominant step in fibril formation, for which the activation energy barrier is entirely entropic. In addition, we found that the presence of heparin, a representative glycosaminoglycan, accelerated fibril formation kinetics and enhanced the yield of apoA-IV 1−70 fibrils, and the positively charged residues K58-K59 play a critical role in heparin interaction. Overall, our results suggest that the strong amyloid-forming propensity of the N-terminal fragment of apoA-IV may play a key role in amyloid deposition associated with apoA-IV amyloidosis. en-copyright= kn-copyright= en-aut-name=NambaNorihiro en-aut-sei=Namba en-aut-mei=Norihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DanjoTokiko en-aut-sei=Danjo en-aut-mei=Tokiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitagawaYuichiro en-aut-sei=Kitagawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaitoYoshito en-aut-sei=Naito en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhgitaTakashi en-aut-sei=Ohgita en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimanouchiToshinori en-aut-sei=Shimanouchi en-aut-mei=Toshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaitoHiroyuki en-aut-sei=Saito en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University kn-affil= affil-num=2 en-affil=Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University kn-affil= affil-num=3 en-affil=Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University kn-affil= affil-num=4 en-affil=Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University kn-affil= affil-num=5 en-affil=Center for Instrumental Analysis, Kyoto Pharmaceutical University kn-affil= affil-num=6 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University kn-affil= en-keyword=Apolipoprotein A-IV kn-keyword=Apolipoprotein A-IV en-keyword=Aggregation kn-keyword=Aggregation en-keyword=Amyloid fibril kn-keyword=Amyloid fibril en-keyword=Heparin kn-keyword=Heparin END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue= article-no= start-page=1680076 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prolonged TNF-α stimulation induces a PD-1–associated exhaustion-like phenotype in mesenchymal stromal cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mesenchymal stromal cells (MSCs) have emerged as promising therapeutic agents for inflammatory diseases because of their potent immunomodulatory properties. Although acute inflammation transiently enhances MSC functionality, the impact of chronic inflammatory exposure remains poorly defined. In this study, we investigated the effects of sustained TNF-α stimulation and indirect co-culture with M1 macrophages on MSC behavior. Comprehensive gene expression profiling was performed to assess the changes in immunoregulatory, apoptotic, and metabolic pathways. To determine functional reversibility, we also evaluated MSCs following the withdrawal of TNF-α. Short-term exposure led to upregulation of Tgf-β, Il-10, and Fasl, whereas prolonged stimulation suppressed these genes and significantly increased the expression of immune checkpoint genes Pd-1 and Ctla-4, indicative of an exhaustion-like phenotype. This phenotypic shift was associated with sustained NF-κB activation, upregulation of Stat3 and Ap-1, suppression of mTORC1/2 components, decreased Pd-l1 expression, and increased Pd-1 expression, raising the possibility that PD-1 upregulation is associated with MSC dysfunction under chronic inflammatory stress. These findings revealed that prolonged stimulation (48 h) induces an exhaustion-like dysfunction state in MSCs, characterized by checkpoint activation, transcriptional repression, and metabolic dysfunction. PD-1 may serve as a biomarker associated with inflammation-induced MSC impairment. en-copyright= kn-copyright= en-aut-name=MatsunagaNaoya en-aut-sei=Matsunaga en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkiyamaKentaro en-aut-sei=Akiyama en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MunAung Ye en-aut-sei=Mun en-aut-mei=Aung Ye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZouTinling en-aut-sei=Zou en-aut-mei=Tinling kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItoKazuki en-aut-sei=Ito en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TagashiraRuji en-aut-sei=Tagashira en-aut-mei=Ruji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KubokiTakuo en-aut-sei=Kuboki en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=immune checkpoint kn-keyword=immune checkpoint en-keyword=immunoregulatory dysfunction kn-keyword=immunoregulatory dysfunction en-keyword=mesenchymal stromal cells (MSCs) kn-keyword=mesenchymal stromal cells (MSCs) en-keyword=prolonged inflammatory stimulation kn-keyword=prolonged inflammatory stimulation en-keyword=TNF-α (tumor necrosis factor-alpha) kn-keyword=TNF-α (tumor necrosis factor-alpha) END start-ver=1.4 cd-journal=joma no-vol=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–Guérin kn-keyword=Bacille Calmette–Guérin 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=80 cd-vols= no-issue=4 article-no= start-page=259 end-page=264 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Spinous Process Plate Fixation Alone for an AO Spine Osteoporotic Fracture (OF) 5 Diffuse Idiopathic Skeletal Hyperostosis (DISH)-Associated Thoracolumbar Fracture in a Nonagenarian en-subtitle= kn-subtitle= en-abstract= kn-abstract=Diffuse idiopathic skeletal hyperostosis (DISH) predisposes the spine to highly unstable fractures because of long lever-arm biomechanics. Unstable injuries, including AO Spine Osteoporotic Fracture (OF) type 5, are typically treated with long-segment posterior instrumentation; however, pedicle-screw fixation may be infeasible in very elderly patients with severe osteoporosis, critically narrow pedicles, and/or significant comorbidities. A 93-year-old Japanese woman presented with severe back pain without apparent trauma. Computed tomography (CT) revealed a T12 fracture with DISH, classified as OF5. The pedicles were critically narrow (3.7-4.1 mm), and dual-energy X-ray absorptiometry confirmed severe osteoporosis. Because conventional pedicle-screw fixation was considered technically unsafe and excessively invasive, limited posterior stabilization was performed using a single spinous process plate spanning T10-L1. The operative time was 48 min and the estimated blood loss was 10 ml. Immediate postoperative CT confirmed appropriate implant positioning and maintained alignment. At the 1-year follow-up, CT demonstrated solid bony union with preserved alignment and no implant failure; the patient had remained pain-free and ambulatory. This case demonstrates that spinous process-plate fixation can be a minimally invasive salvage option for carefully selected very-elderly patients with DISH when pedicle-screw instrumentation is not feasible. en-copyright= kn-copyright= en-aut-name=YabunoSatoru en-aut-sei=Yabuno en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YunokiMasatoshi en-aut-sei=Yunoki en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakeuchiSaori en-aut-sei=Takeuchi en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirashitaKoji en-aut-sei=Hirashita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Neurosurgery, Kagawa Rosai Hospital kn-affil= affil-num=2 en-affil=Department of Neurosurgery, Kagawa Rosai Hospital kn-affil= affil-num=3 en-affil=Department of Neurosurgery, Kagawa Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Neurosurgery, Kagawa Rosai Hospital kn-affil= en-keyword=DISH kn-keyword=DISH en-keyword=vertebral fracture kn-keyword=vertebral fracture en-keyword=osteoporosis kn-keyword=osteoporosis en-keyword=spinous process plate kn-keyword=spinous process plate END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=4 article-no= start-page=253 end-page=257 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=Hemorrhage from a Jejunal Lymphangioma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Lymphangioma is a benign tumor arising from lymphatic vessel proliferation and most commonly occurs in the head, neck, or axilla. Involvement of the small intestine is rare and is often overlooked as a source of obscure gastrointestinal bleeding. Because jejunal lymphangiomas frequently present with nonspecific symptoms and may escape detection by conventional upper and lower gastrointestinal endoscopy or cross-sectional imaging, diagnosis is often delayed. Advances in balloon-assisted enteroscopy have enabled direct visualization of small intestinal lesions, facilitating accurate diagnosis and appropriate therapeutic decision-making. Here, we report a case of jejunal lymphangioma presenting with severe anemia due to active bleeding, which was detected by double-balloon endoscopy and successfully managed by laparoscopic-assisted resection. This case highlights the importance of considering small intestinal lymphangioma in the differential diagnosis of unexplained gastrointestinal bleeding and underscores the clinical utility of deep enteroscopy in identifying rare but clinically significant small bowel tumors. en-copyright= kn-copyright= en-aut-name=IshikamiSachiko en-aut-sei=Ishikami en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TamuraShuta en-aut-sei=Tamura en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TabuchiMotoyasu en-aut-sei=Tabuchi en-aut-mei=Motoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoNao en-aut-sei=Yamamoto en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkamotoYuki en-aut-sei=Okamoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshimatsuRika en-aut-sei=Yoshimatsu en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoManabu en-aut-sei=Matsumoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwataJun en-aut-sei=Iwata en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=4 en-affil=Department of General Medicine, Kochi Health Sciences Center kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Radiology, Kochi Health Sciences Center kn-affil= affil-num=7 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=8 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= en-keyword=jejunal lymphangioma kn-keyword=jejunal lymphangioma en-keyword=double-balloon endoscopy kn-keyword=double-balloon endoscopy en-keyword=surgery kn-keyword=surgery END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=4 article-no= start-page=227 end-page=231 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Impact of Migraine on Cerebral Artery Dissection en-subtitle= kn-subtitle= en-abstract= kn-abstract=The impact of migraines as a risk factor for cervicocerebral artery dissection was retrospectively investigated in patients who had a cervicocerebral artery dissection. We first evaluated the patients’ medical records and history of migraine and then calculated the proportion of patients with migraine as well as the relevant vascular risk factors. The prevalence of migraine with respect to the location of the cervicocerebral artery dissection was also identified. Sixty-two patients (37 men, 25 women) had both a cerebral artery dissection and a record of migraine. Among them, 93.5% presented with an isolated headache, and 6.5% presented with a related stroke. Regarding the locations of the artery dissection, 56 (90.3%) were in the intracranial vertebral artery (VA), three (4.8%) were in the internal carotid artery, and one case each (1.6%) was in an anterior cerebral artery, basilar artery (BA), and both the VA and BA. Among the patients with VA dissection, 42 (73.7%) presented with migraines. Among the four patients with dissection of an artery of anterior circulation, only one (25%) had a migraine history. The frequency of migraines tended to be higher in the patients with VA dissection compared to those with a dissection of arteries of anterior circulation. These data suggest that (i) migraine is a potent risk factor for cerebral artery dissection, especially intracranial VA dissection, and (ii) the intracranial VA may be more susceptible to dissection compared to arteries of anterior circulation. en-copyright= kn-copyright= en-aut-name=KashiharaKenichi en-aut-sei=Kashihara en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamaguchiToshikazu en-aut-sei=Hamaguchi en-aut-mei=Toshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakedaYasuko en-aut-sei=Takeda en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Okayama Neurology Clinic kn-affil= affil-num=2 en-affil=Department of Neurology, Okayama Kyokuto Hospital kn-affil= affil-num=3 en-affil=Okayama Neurology Clinic kn-affil= en-keyword=cervicocerebral artery dissection kn-keyword=cervicocerebral artery dissection en-keyword=isolated headache kn-keyword=isolated headache en-keyword=migraine kn-keyword=migraine en-keyword=risk factor kn-keyword=risk factor en-keyword=vertebral artery kn-keyword=vertebral artery END start-ver=1.4 cd-journal=joma no-vol=131 cd-vols= no-issue=8 article-no= start-page=e2026JB034225 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260816 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Spin Transition of Ferric Iron in Silicate Glasses Inferred by High‐Pressure Electrical Conductivity Measurements en-subtitle= kn-subtitle= en-abstract= kn-abstract=Silicate melt has been proposed to exist near the base of the mantle and has been invoked to explain seismic and electrical conductivity anomalies observed near the core-mantle boundary; however, its presence and stability under lowermost-mantle conditions remain uncertain. Here we report high-pressure electrical conductivity measurements of Fe2+- and Fe3+-bearing pyroxene glasses (Fe3+/ΣFe ≈ 0.5), used as analogs of silicate melts, up to megabar pressures at room temperature. At lower pressures, conductivity increases with pressure and iron content, consistent with electron-hole hopping between Fe2+ and Fe3+. Above 77–85 GPa, all samples show a marked conductivity decrease, suggesting a pressure-induced spin transition of Fe3+. Previous studies have suggested that lower-mantle silicate melts may be enriched in Fe3+, and iron spin-state changes may modify iron partitioning between silicate melts and coexisting crystalline phases. Therefore, the Fe3+ spin transition inferred here may affect the evolution of deep-mantle melts through pressure-dependent changes in iron partitioning behavior. en-copyright= kn-copyright= en-aut-name=MashinoIzumi en-aut-sei=Mashino en-aut-mei=Izumi 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=KitaoShinji en-aut-sei=Kitao en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuiTakaya en-aut-sei=Mitsui en-aut-mei=Takaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasudaRyo en-aut-sei=Masuda en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SetoMakoto en-aut-sei=Seto en-aut-mei=Makoto 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=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=4 en-affil=Synchrotron Radiation Research Center, Kansai Photon Science Institute, Quantum Beam Science Research Directorate, National Institutes for Quantum Science and Technology kn-affil= affil-num=5 en-affil=Graduate School of Science and Technology, Hirosaki University kn-affil= affil-num=6 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= en-keyword=high pressure kn-keyword=high pressure en-keyword=electrical conductivity kn-keyword=electrical conductivity en-keyword=silicate glass kn-keyword=silicate glass en-keyword=diamond anvil cell kn-keyword=diamond anvil cell en-keyword=the Earth's mantle kn-keyword=the Earth's mantle en-keyword=ferric iron kn-keyword=ferric iron END start-ver=1.4 cd-journal=joma no-vol=141 cd-vols= no-issue= article-no= start-page=254 end-page=261 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=Transient loss of wakefulness with falls in temporal lobe epilepsy: A retrospective single-centre study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Focal impaired awareness seizures in temporal lobe epilepsy (TLE) typically involve behavioural arrest and automatisms with preserved posture. However, some patients can exhibit a transient loss of wakefulness with fall without any overt motor manifestations, a phenomenon previously described as “temporal lobe syncope.” However, previous reports did not always rigorously exclude FBTCS or ictal asystole. Herein, we aimed to reappraise this semiology by excluding these conditions using simultaneous video-electroencephalogram (VEEG) and electrocardiogram (ECG), clarifying its clinical characteristics.
Methods: We retrospectively analysed 65 patients with drug-resistant TLE who underwent surgery between April 2017 and December 2025. Seizures with transient loss of wakefulness with fall were defined as events without generalized motor manifestations or ECG changes, such as bradycardia or asystole. Outcomes were assessed using the ILAE seizure outcome classification.
Results: Three of 65 patients exhibited seizures characterised by transient loss of wakefulness with fall. All patients were clinically diagnosed with left TLE, and these seizures developed at least 10 years after epilepsy onset. Simultaneous VEEG and ECG excluded ictal asystole and FBTCS as the causes of the falls. One patient achieved seizure freedom after anterior temporal lobectomy, whereas the other two patients did not achieve seizure freedom after surgery.
Conclusion: Our findings suggest that transient loss of wakefulness in TLE patients may represent a distinct seizure semiology that should be differentiated from impaired awareness and from other causes of fall. Although the underlying mechanism remains uncertain, distinguishing wakefulness from awareness may provide a useful conceptual framework for understanding disorders of consciousness during epileptic seizures. en-copyright= kn-copyright= en-aut-name=IzumiharaKohei en-aut-sei=Izumihara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SasakiTatsuya en-aut-sei=Sasaki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkazakiYosuke en-aut-sei=Okazaki en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanimotoShun en-aut-sei=Tanimoto en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaijoTomoya en-aut-sei=Saijo en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KinKyohei en-aut-sei=Kin en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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= en-keyword=Temporal lobe epilepsy kn-keyword=Temporal lobe epilepsy en-keyword=Semiology kn-keyword=Semiology en-keyword=Drug-resistant epilepsy kn-keyword=Drug-resistant epilepsy en-keyword=Wakefulness kn-keyword=Wakefulness en-keyword=Temporal lobe syncope kn-keyword=Temporal lobe syncope 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= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260514 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Updated ENIGMA recommendations for reporting germline variants in cancer susceptibility genes and their translation into twenty languages en-subtitle= kn-subtitle= en-abstract= kn-abstract=Genetic testing for cancer susceptibility underpins precision cancer prevention and care. Gaps in the healthcare providers’ genetic literacy and an ambiguous lexicon for variant description may hinder proper delivery and clinical application of consistently trustworthy test results. The Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) international consortium supports controlled terminology and recommends a framework for reporting germline variants in cancer susceptibility genes, using breast cancer as an exemplar. Moving forward towards terminological coherence across disciplines and borders, the ENIGMA Clinical Working Group launched a multinational effort to release consortium-approved translations of the published recommendations. The herein reported Vocabulary Translation Project offered an opportunity to reappraise and align the reference text to the recent BRCA1 and BRCA2 specifications to the American College of Medical Genetics and Genomics/Association for Molecular Pathology rules by the ENIGMA Variant Curation Expert Panel and to highlight country-specific differences in breast cancer risk assessment and management. The updated recommendations and their 20 translations are now provided as easy to handle documents, covering 11 of the most widely spoken languages in the world. They will contribute to minimised erroneous inferences, more informed decision-making, improved health outcomes and equity in the use of genetic testing for cancer predisposition and in translational oncology. en-copyright= kn-copyright= en-aut-name=De NicoloArcangela en-aut-sei=De Nicolo en-aut-mei=Arcangela kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EcclesDiana M en-aut-sei=Eccles en-aut-mei=Diana M kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AaltonenKirsimari en-aut-sei=Aaltonen en-aut-mei=Kirsimari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AlhopuroPia en-aut-sei=Alhopuro en-aut-mei=Pia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AriansenSarah Louise en-aut-sei=Ariansen en-aut-mei=Sarah Louise kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BiancolellaMichela en-aut-sei=Biancolella en-aut-mei=Michela kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=CaputoSandrine M en-aut-sei=Caputo en-aut-mei=Sandrine M kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CaronOlivier en-aut-sei=Caron en-aut-mei=Olivier kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=CavalliPietro en-aut-sei=Cavalli en-aut-mei=Pietro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ChiangJianbang en-aut-sei=Chiang en-aut-mei=Jianbang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ClaesKathleen B M en-aut-sei=Claes en-aut-mei=Kathleen B M kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=CuaresmaEdgar Christian S en-aut-sei=Cuaresma en-aut-mei=Edgar Christian S kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=de la HoyaMiguel en-aut-sei=de la Hoya en-aut-mei=Miguel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=De PauwAntoine en-aut-sei=De Pauw en-aut-mei=Antoine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=DíezOrland en-aut-sei=Díez en-aut-mei=Orland kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Domínguez-ValentinMev en-aut-sei=Domínguez-Valentin en-aut-mei=Mev kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=EhrencronaHans en-aut-sei=Ehrencrona en-aut-mei=Hans kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FjeldværMagnhild K en-aut-sei=Fjeldvær en-aut-mei=Magnhild K kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FostiraFlorentia en-aut-sei=Fostira en-aut-mei=Florentia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FranciaMarie Belle D en-aut-sei=Francia en-aut-mei=Marie Belle D kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=Galego-CarroJavier en-aut-sei=Galego-Carro en-aut-mei=Javier kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=Gómez GarcíaEncarna B en-aut-sei=Gómez García en-aut-mei=Encarna B kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HassanNur Tiara en-aut-sei=Hassan en-aut-mei=Nur Tiara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HaukeJan en-aut-sei=Hauke en-aut-mei=Jan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 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=25 ORCID= en-aut-name=HuangXin en-aut-sei=Huang en-aut-mei=Xin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=Ilagan-CargulloElaine Marisse H en-aut-sei=Ilagan-Cargullo en-aut-mei=Elaine Marisse H kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=ImotoIssei en-aut-sei=Imoto en-aut-mei=Issei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=JonnagadlaSowmya en-aut-sei=Jonnagadla en-aut-mei=Sowmya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=KarthikeyanManasadevi en-aut-sei=Karthikeyan en-aut-mei=Manasadevi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=KleiblovaPetra en-aut-sei=Kleiblova en-aut-mei=Petra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=KonstantopoulouIrene en-aut-sei=Konstantopoulou en-aut-mei=Irene kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KowalikArtur en-aut-sei=Kowalik en-aut-mei=Artur kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=KvistAnders en-aut-sei=Kvist en-aut-mei=Anders kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=LesueurFabienne en-aut-sei=Lesueur en-aut-mei=Fabienne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=LiShao-Tzu en-aut-sei=Li en-aut-mei=Shao-Tzu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=López-FernándezAdrià en-aut-sei=López-Fernández en-aut-mei=Adrià 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kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=SolanoAngela R en-aut-sei=Solano en-aut-mei=Angela R kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=SoukupovaJana en-aut-sei=Soukupova en-aut-mei=Jana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=SureshPriyadharshini d/o en-aut-sei=Suresh en-aut-mei=Priyadharshini d/o kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= en-aut-name=SzczepaniakMagdalena en-aut-sei=Szczepaniak en-aut-mei=Magdalena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=56 ORCID= en-aut-name=TanYen Y en-aut-sei=Tan en-aut-mei=Yen Y kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=57 ORCID= en-aut-name=TeoSoo Hwang en-aut-sei=Teo en-aut-mei=Soo Hwang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=58 ORCID= en-aut-name=ThamEmma en-aut-sei=Tham en-aut-mei=Emma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=59 ORCID= en-aut-name=ThomassenMads en-aut-sei=Thomassen en-aut-mei=Mads kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=60 ORCID= en-aut-name=TsaousisGeorgios en-aut-sei=Tsaousis en-aut-mei=Georgios kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=61 ORCID= en-aut-name=HansenThomas van Overeem en-aut-sei=Hansen en-aut-mei=Thomas van Overeem kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=62 ORCID= en-aut-name=VegaAna en-aut-sei=Vega en-aut-mei=Ana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=63 ORCID= en-aut-name=Velasco-SampedroEladio A en-aut-sei=Velasco-Sampedro en-aut-mei=Eladio A kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=64 ORCID= en-aut-name=WangensteenTeresia en-aut-sei=Wangensteen en-aut-mei=Teresia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=65 ORCID= en-aut-name=WappenschmidtBarbara en-aut-sei=Wappenschmidt en-aut-mei=Barbara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=66 ORCID= en-aut-name=YannoukakosDrakoulis en-aut-sei=Yannoukakos en-aut-mei=Drakoulis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=67 ORCID= en-aut-name=YoonSook-Yee en-aut-sei=Yoon en-aut-mei=Sook-Yee kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=68 ORCID= en-aut-name=SpurdleAmanda B en-aut-sei=Spurdle en-aut-mei=Amanda B kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=69 ORCID= en-aut-name=RadicePaolo en-aut-sei=Radice en-aut-mei=Paolo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=70 ORCID= affil-num=1 en-affil=Department of Experimental Oncology, Unit of Predictive Medicine: Molecular Bases of Genetic Risk, Fondazione IRCCS Istituto Nazionale dei Tumori kn-affil= affil-num=2 en-affil=Faculty of Medicine, University of Southampton kn-affil= affil-num=3 en-affil=Duodecim Medical Publications Ltd kn-affil= affil-num=4 en-affil=HUS Diagnostic Center, Laboratory of Genetics, Helsinki University Hospital and University of Helsinki kn-affil= affil-num=5 en-affil=Department of Medical Genetics, Oslo University Hospital kn-affil= affil-num=6 en-affil=Department of Biology, University of Rome Tor Vergata kn-affil= affil-num=7 en-affil=Department of Genetics, Institut Curie kn-affil= affil-num=8 en-affil=Département de Médecine Oncologique, Gustave Roussy kn-affil= affil-num=9 en-affil=Medical Genetics, IRCCS Humanitas Research Hospital kn-affil= affil-num=10 en-affil=Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore kn-affil= affil-num=11 en-affil=Center for Medical Genetics, Ghent University Hospital kn-affil= affil-num=12 en-affil=St. Luke’s Medical Center kn-affil= affil-num=13 en-affil=Hospital Clínico San Carlos, Molecular Oncology Laboratory, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos kn-affil= affil-num=14 en-affil=Department of Genetics, Institut Curie kn-affil= affil-num=15 en-affil=Vall d’Hebron Hospital Universitari, Area of Clinical and Molecular Genetics, Vall d’Hebron Barcelona Hospital Campus kn-affil= affil-num=16 en-affil=Institute of Cancer Research, Department of Tumor Biology, The Norwegian Radium Hospital kn-affil= affil-num=17 en-affil=Department of Clinical Genetics, Pathology and Molecular Diagnostics, Skåne University Hospital kn-affil= affil-num=18 en-affil=Department of Medical Genetics, Oslo University Hospital kn-affil= affil-num=19 en-affil=INRASTES, Human Molecular Genetics Laboratory, National Centre for Scientific Research-Demokritos kn-affil= affil-num=20 en-affil=St. Luke’s Medical Center kn-affil= affil-num=21 en-affil=Fundación Pública Galega de Medicina Xenómica and Instituto de Investigación Sanitaria de Santiago de Compostela kn-affil= affil-num=22 en-affil=Department of Clinical Genetics, Maastricht University Medical Centre kn-affil= affil-num=23 en-affil=Cancer Research Malaysia kn-affil= affil-num=24 en-affil=Faculty of Medicine and Center for Familial Breast and Ovarian Cancer, University of Cologne, University Hospital Cologne kn-affil= affil-num=25 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Department of Clinical Genomic Medicine, Okayama University kn-affil= affil-num=26 en-affil=Department of Breast Surgery, Peking Union Medical College Hospital kn-affil= affil-num=27 en-affil=St. Luke’s Medical Center kn-affil= affil-num=28 en-affil=Aichi Cancer Center Research Institute kn-affil= affil-num=29 en-affil=Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore, Si kn-affil= affil-num=30 en-affil=Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore kn-affil= affil-num=31 en-affil=Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague kn-affil= affil-num=32 en-affil=INRASTES, Human Molecular Genetics Laboratory, National Centre for Scientific Research-Demokritos kn-affil= affil-num=33 en-affil=Department of Molecular Diagnostics, Holy Cross Cancer Centre kn-affil= affil-num=34 en-affil=Department of Clinical Sciences Lund, Division of Oncology, Lund University kn-affil= affil-num=35 en-affil=PSL Research University kn-affil= affil-num=36 en-affil=Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore kn-affil= affil-num=37 en-affil=Hereditary Cancer Genetics Group, Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebron Institute of Oncology (VHIO) kn-affil= affil-num=38 en-affil=Center for Medical Genetics, Masaryk Memorial Cancer Institute kn-affil= affil-num=39 en-affil=Univ Rouen Normandie, Inserm U1245 kn-affil= affil-num=40 en-affil=Department of Human Genetics, Radboud University Medical Center kn-affil= affil-num=41 en-affil=Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences kn-affil= affil-num=42 en-affil=Department of Oncogenetics, MRC Holland kn-affil= affil-num=43 en-affil=Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute kn-affil= affil-num=44 en-affil=HUS Diagnostic Center, Laboratory of Genetics, Helsinki University Hospital and University of Helsinki kn-affil= affil-num=45 en-affil=Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore kn-affil= affil-num=46 en-affil=Molecular Oncology Research Center, Barretos Cancer Hospital kn-affil= affil-num=47 en-affil=Molecular Diagnostics and Clinical Cancer Research Centre, Aalborg University Hospital kn-affil= affil-num=48 en-affil=St. Luke’s Medical Center kn-affil= affil-num=49 en-affil=Fundación Pública Galega de Medicina Xenómica and Instituto de Investigación Sanitaria de Santiago de Compostela kn-affil= affil-num=50 en-affil=Department of Medical Oncology, A.C. Camargo Cancer Center kn-affil= affil-num=51 en-affil=Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Medical University of Vienna kn-affil= affil-num=52 en-affil=Genetic Clinic, Holy Cross Cancer Centre kn-affil= affil-num=53 en-affil=Departmento de Analisis Clinicos, Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno" (CEMIC) kn-affil= affil-num=54 en-affil=Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague kn-affil= affil-num=55 en-affil=Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore kn-affil= affil-num=56 en-affil=Department of Molecular Diagnostics, Holy Cross Cancer Centre kn-affil= affil-num=57 en-affil=Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Medical University of Vienna kn-affil= affil-num=58 en-affil=Cancer Research Malaysia kn-affil= affil-num=59 en-affil=Department of Clinical Genetics and Genomics, Karolinska University Hospital kn-affil= affil-num=60 en-affil=Department of Clinical Genetics, Odense University Hospital kn-affil= affil-num=61 en-affil=Genekor Medical S.A kn-affil= affil-num=62 en-affil=Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet kn-affil= affil-num=63 en-affil=Fundación Pública Galega de Medicina Xenómica and Instituto de Investigación Sanitaria de Santiago de Compostela kn-affil= affil-num=64 en-affil=Instituto de Biología y Genética Molecular, Splicing and Genetic Susceptibility to Cancer, Consejo Superior de Investigaciones Científicas - Universidad de Valladolid (CSIC-UVa) kn-affil= affil-num=65 en-affil=Department of Medical Genetics, Oslo University Hospital kn-affil= affil-num=66 en-affil=Faculty of Medicine and Center for Familial Breast and Ovarian Cancer, University of Cologne, University Hospital Cologne kn-affil= affil-num=67 en-affil=INRASTES, Human Molecular Genetics Laboratory, National Centre for Scientific Research-Demokritos kn-affil= affil-num=68 en-affil=Cancer Research Malaysia kn-affil= affil-num=69 en-affil=Population Health Program, QIMR Berghofer Medical Research Institute kn-affil= affil-num=70 en-affil=Department of Experimental Oncology, Unit of Predictive Medicine: Molecular Bases of Genetic Risk, Fondazione IRCCS Istituto Nazionale dei Tumori 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=20260711 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical utility of diagnosing Lynch syndrome in gynecologic oncology: a joint statement from four Japanese academic societies en-subtitle= kn-subtitle= en-abstract= kn-abstract=Lynch syndrome (LS) is an autosomal dominant cancer predisposition syndrome, associated with substantially increased risks of colorectal and gynecologic malignancies. Endometrial cancer may serve as a sentinel cancer for LS, placing gynecologists and gynecologic oncologists in a key position for early recognition and long-term management. This joint statement was developed through a multidisciplinary process involving the Japan Society of Gynecologic Oncology, the Japan Society of Clinical Oncology, the Japanese Society of Hereditary Tumors, and the Japanese Society for Cancer of the Colon and Rectum. It aims to clarify the clinical utility of diagnosing LS in gynecologic oncology within the Japanese healthcare system. We outline a tumor-first paradigm in which universal mismatch repair immunohistochemistry and/or microsatellite instability testing for endometrial cancer facilitates LS detection and provides actionable biomarkers for systemic therapy. This statement summarizes the clinical impact of LS diagnosis across gynecologic oncology. We highlight patterns of synchronous and metachronous malignancies and the prevalence of LS in ovarian cancer, particularly in endometrioid and clear–cell subtypes. We discuss surgical implications, including risk-reducing hysterectomy with bilateral salpingo-oophorectomy, consideration of concomitant gynecologic risk-reducing surgery during colorectal cancer resection, and individualized ovarian preservation in selected early-stage endometrial cancer or atypical endometrial hyperplasia. We also review the treatment relevance of deficient mismatch repair/microsatellite instability-high status for immune checkpoint inhibitors and emerging fertility-preserving approaches, and address surveillance, cascade testing for relatives, implementation barriers, and the need for multidisciplinary pathways and healthcare system–level support to ensure equitable access to genetic counseling and testing. en-copyright= kn-copyright= en-aut-name=SatoShinya en-aut-sei=Sato en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MasudaKenta en-aut-sei=Masuda en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OdaKatsutoshi en-aut-sei=Oda en-aut-mei=Katsutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuwataTakeshi en-aut-sei=Kuwata en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakajimaTakeshi en-aut-sei=Nakajima en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamadaMasayoshi en-aut-sei=Yamada en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamaguchiTatsuro en-aut-sei=Yamaguchi en-aut-mei=Tatsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MandaiMasaki en-aut-sei=Mandai en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakayaKohji en-aut-sei=Tanakaya en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshidaHideyuki en-aut-sei=Ishida en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YoshinoTakayuki en-aut-sei=Yoshino en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkamotoAikou en-aut-sei=Okamoto en-aut-mei=Aikou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Tottori University kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Division of Integrative Genomics, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Genetic Medicine and Services, National Cancer Center Hospital East kn-affil= affil-num=5 en-affil=Division of Hereditary Tumors, Department of Genetic Oncology, Osaka International Cancer Institute kn-affil= affil-num=6 en-affil=Endoscopy Division, National Cancer Center Hospital kn-affil= affil-num=7 en-affil=Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=8 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Surgery, National Hospital Organization Iwakuni Medical Center kn-affil= affil-num=11 en-affil=Department of Clinical Genetics, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East kn-affil= affil-num=13 en-affil=Department of Obstetrics and Gynecology, Sanno Hospital, International University of Health and Welfare kn-affil= en-keyword=Lynch syndrome kn-keyword=Lynch syndrome en-keyword=Endometrial cancer kn-keyword=Endometrial cancer en-keyword=Ovarian cancer kn-keyword=Ovarian cancer en-keyword=Mismatch repair kn-keyword=Mismatch repair en-keyword=Microsatellite instability kn-keyword=Microsatellite instability en-keyword=Immune checkpoint inhibitor kn-keyword=Immune checkpoint inhibitor END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=8 article-no= start-page=494 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260807 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oral Supplementation of Bacillus subtilis Attenuated Alveolar Bone Loss in a Mouse Model of Ligature-Induced Periodontitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: This study aimed to investigate the effects of oral Bacillus subtilis (BS) on alveolar bone loss, intestinal morphology, and gut microbiota in a mouse model of ligature-induced periodontitis. Methods: A total of 24 male C57BL/6J mice (6 weeks old) were allocated to control, periodontitis (P), BS, and BS+P groups. Periodontitis was induced by bilateral ligation of maxillary second molars, and BS was orally administered for 18 consecutive days. Gut microbiota composition was analyzed by 16S rDNA sequencing, alveolar bone loss and gut morphology were evaluated using ImageJ version 1.54g, and ELISA-detectable serum vitamin D metabolite concentrations were measured using an enzyme-linked immunosorbent assay. Results: Compared with the P group, the BS+P group showed reduced bone loss. Serum vitamin D metabolite concentrations, small-intestine villus height, and villus height-to-crypt depth ratios were higher in the BS+P group. In gut microbiota, alpha diversity differed significantly among groups based on the Shannon index. Bray–Curtis-based beta diversity differed significantly among groups. Conclusions: Oral supplementation of BS attenuated the progression of ligature-induced periodontitis in a mouse model, and changes in gut microbiota may be associated with this effect. en-copyright= kn-copyright= en-aut-name=ZhangYixuan en-aut-sei=Zhang en-aut-mei=Yixuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ToyamaNaoki en-aut-sei=Toyama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NurhamimMohammad en-aut-sei=Nurhamim en-aut-mei=Mohammad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakaharaMomoko en-aut-sei=Nakahara en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukuharaDaiki en-aut-sei=Fukuhara en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaruyamaTakayuki en-aut-sei=Maruyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Dental School, Okayama University kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Dental School, Okayama University kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Bacillus subtilis kn-keyword=Bacillus subtilis en-keyword=periodontitis kn-keyword=periodontitis en-keyword=alveolar bone loss kn-keyword=alveolar bone loss en-keyword=gut microbiota kn-keyword=gut microbiota en-keyword=intestinal morphology kn-keyword=intestinal morphology en-keyword=vitamin D kn-keyword=vitamin D en-keyword=mouse model kn-keyword=mouse model END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue= article-no= start-page=102156 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pembrolizumab-based systemic therapy associated with opportunities for subsequent local treatment in advanced or recurrent neuroendocrine carcinoma of the cervix: a five-case series en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Neuroendocrine carcinoma (NEC) of the cervix is a rare, highly aggressive malignancy with limited evidence supporting immune checkpoint blockade. We evaluated the clinical activity of pembrolizumab-based therapy in patients with advanced or recurrent cervical NEC.
Methods: We retrospectively reviewed five consecutive patients with advanced or recurrent cervical NEC treated with pembrolizumab-based therapy at Okayama University Hospital between November 2022 and April 2025. Clinical characteristics, radiologic responses, molecular profiles, adverse events, local treatments, and survival outcomes were analyzed.
Results: The median age was 52 years. Three patients had newly diagnosed stage IVB disease, and two had recurrent metastatic disease after radical surgery and postoperative irinotecan plus cisplatin chemotherapy. All patients received paclitaxel plus carboplatin with pembrolizumab. An objective response was observed in all patients, including one complete response and four partial responses according to RECIST version 1.1. The median maximum tumor shrinkage was 78.5%, and median progression-free survival was 10.0 months. Comprehensive genomic profiling in four patients showed microsatellite-stable tumors with low tumor mutational burden in all evaluated cases. HPV association was supported by HPV16/18 sequences in three patients and diffuse p16 expression in one additional patient. Immune-related adverse events were grade 2 or lower. In three patients, systemic disease control allowed subsequent local treatment, including radiotherapy, conversion surgery, and stereotactic radiotherapy.
Conclusion: Pembrolizumab-based therapy showed encouraging clinical activity despite microsatellite-stable status and low tumor mutational burden in evaluated cases. Sustained systemic disease control may provide an opportunity for multimodal treatment incorporating subsequent local treatment. en-copyright= kn-copyright= en-aut-name=IdaNaoyuki en-aut-sei=Ida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaYui en-aut-sei=Tanaka en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujikawaAtsushi en-aut-sei=Fujikawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaniokaMomoko en-aut-sei=Tanioka en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ImataniRyoko en-aut-sei=Imatani en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TaniYoshinori en-aut-sei=Tani en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiharaHanako en-aut-sei=Sugihara en-aut-mei=Hanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuokaHirofumi en-aut-sei=Matsuoka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkamotoKazuhiro en-aut-sei=Okamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HaragaJunko en-aut-sei=Haraga en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Neuroendocrine carcinoma (NEC) kn-keyword=Neuroendocrine carcinoma (NEC) en-keyword=Cervical cancer kn-keyword=Cervical cancer en-keyword=Pembrolizumab kn-keyword=Pembrolizumab en-keyword=Immunotherapy kn-keyword=Immunotherapy en-keyword=Local intervention kn-keyword=Local intervention en-keyword=Case series kn-keyword=Case series END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=8 article-no= start-page=e0356180 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Study protocol: Effect of inulin supplementation on gut microbiota in patients with oral lichen planus — A double-blind, randomised, placebo-controlled parallel-group trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oral lichen planus is a chronic inflammatory disease of the oral mucosa characterised by immune dysregulation, but its pathogenesis remains incompletely understood and no curative treatment has been established. Our previous work showed that patients with oral lichen planus exhibit gut dysbiosis, including reduced microbial diversity and depletion of butyrate-producing bacteria. Because butyrate promotes regulatory T-cell differentiation and supports immune homeostasis, targeting this dysbiosis may represent a microbiota-directed approach for immune modulation in oral lichen planus. This study aims to investigate the effects of inulin supplementation on the gut microbiota and related immune markers in patients with oral lichen planus. This multicentre, double-blind, randomised, placebo-controlled parallel-group trial will enrol 80 patients with oral lichen planus. Participants will be randomly assigned in a 1:1 ratio to receive either inulin (8 g/day) or a maltose placebo for 4 weeks, in addition to standard care. The primary outcome is the change in the relative abundance of prespecified butyrate-producing gut bacteria from baseline to the end of intervention at Week 6. Secondary outcomes include changes in gut microbiota diversity, salivary microbiota composition, faecal short-chain fatty acid concentrations, peripheral blood regulatory T-cell counts, blood test parameters, and clinical symptoms of oral lichen planus. Analyses will follow the intention-to-treat principle, and between-group differences will be assessed using appropriate statistical methods. This trial is designed to evaluate, in a randomised placebo-controlled setting, whether a microbiota-directed intervention can modify gut microbial profiles and related immune markers in patients with oral lichen planus. The findings are expected to clarify whether inulin supplementation can modify gut microbial profiles and related immunological markers in patients with oral lichen planus. Trial registration: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000060840, registered on 1 April 2026 (https://rctportal.mhlw.go.jp/detail/um?trial_id=UMIN000060840#). en-copyright= kn-copyright= en-aut-name=NambuKoki en-aut-sei=Nambu en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanekoNaoki en-aut-sei=Kaneko en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokomizoShiho en-aut-sei=Yokomizo en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChenHu en-aut-sei=Chen en-aut-mei=Hu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanLijing en-aut-sei=Yan en-aut-mei=Lijing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShiyaoWang en-aut-sei=Shiyao en-aut-mei=Wang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShizumaRyusei en-aut-sei=Shizuma en-aut-mei=Ryusei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwataEiji en-aut-sei=Iwata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhyamaYukiko en-aut-sei=Ohyama en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkagawaShohei en-aut-sei=Akagawa en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawanoShintaro en-aut-sei=Kawano en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MoriyamaMasafumi en-aut-sei=Moriyama en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=2 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=3 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=4 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=5 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=6 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=7 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=10 en-affil=Department of Pediatrics, Kansai Medical University kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=13 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=61 cd-vols= no-issue=9 article-no= start-page=1988 end-page=1991 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=Stomatal Traits in Strawberry Cultivars: Variation among Plant Parts and Associations with Growth and Yield en-subtitle= kn-subtitle= en-abstract= kn-abstract=Stomatal traits are important determinants of photosynthesis and water use; however, their variation among plant parts and cultivars and their relationships with growth and yield in strawberry remain unclear. This study characterized stomatal density and guard cell length among plant parts and across 34 cultivars and examined their associations with growth and yield. Stomata were found not only on the abaxial leaf surface but also on petioles and calyces and occasionally on the adaxial surface of leaves. Both traits varied widely among cultivars and decreased between November and May. Stomatal density was significantly negatively correlated with plant height, estimated leaf area, and total yield in both seasons, whereas guard cell length showed no significant association with these traits. These results suggest that stomatal density may be a more relevant indicator of growth and yield in strawberries and that characterizing stomatal traits across plant parts and cultivars may support breeding and cultivation research. en-copyright= kn-copyright= en-aut-name=Hikawa-EndoMinori en-aut-sei=Hikawa-Endo en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamanakaRyosuke en-aut-sei=Yamanaka en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanoTakayoshi en-aut-sei=Yano en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Okayama University, Graduate School of Environmental, Life, Natural Science and Technology kn-affil= affil-num=2 en-affil=Western Region Agricultural Research Center, NARO kn-affil= affil-num=3 en-affil=Western Region Agricultural Research Center, NARO kn-affil= en-keyword=stomatal density kn-keyword=stomatal density en-keyword=guard cell length kn-keyword=guard cell length en-keyword=plant growth kn-keyword=plant growth en-keyword=yield kn-keyword=yield END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue=4 article-no= start-page=538 end-page=549 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202607 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enhancement of antioxidant function in various organs in mice using combined thermal and radon inhalation treatment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Enhancing antioxidant function is a key strategy for preventing and treating oxidative stress-related diseases. Radon inhalation and thermal treatment (TT) increase the levels of antioxidant enzymes, such as superoxide dismutase (SOD). The positive effects of this combination on pain-related diseases have been reported; however, few studies have elucidated the underlying mechanisms. In this study, we examined the enhancement of antioxidant function in various organs of mice subjected to combined TT and radon inhalation. The mice were placed in an incubator once daily for 40 min at 38.5 ± 0.5°C and treated for 1, 3 and 7 days. The mice then inhaled radon at a concentration of 2000 Bq/m3 for 24 h. The characteristic changes in antioxidant function following combined TT and radon inhalation could be categorized into four groups: (i) increased antioxidant function in the brain and colon; (ii) increased or decreased antioxidant function, as observed in the kidney; (iii) decreased antioxidant function, such as in the lungs and (iv) no changes, such as in the small intestine, spleen, pancreas, heart, liver and stomach. Additionally, SOD may be the antioxidant enzyme most sensitive to combined TT and radon treatment. Collectively, the combined treatment may be the most effective in activating antioxidative functions in the brain and colon. This study provides new insights into the effects of combined TT and radon inhalation. en-copyright= kn-copyright= en-aut-name=MiyanagaShogo en-aut-sei=Miyanaga en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaAyumi en-aut-sei=Tanaka en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakenakaReiju en-aut-sei=Takenaka en-aut-mei=Reiju kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaoeShota en-aut-sei=Naoe en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotoShuna en-aut-sei=Goto en-aut-mei=Shuna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NaganoMitsuki en-aut-sei=Nagano en-aut-mei=Mitsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanoKotaro en-aut-sei=Tano en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanzakiNorie en-aut-sei=Kanzaki en-aut-mei=Norie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakodaAkihiro en-aut-sei=Sakoda en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamaokaKiyonori en-aut-sei=Yamaoka en-aut-mei=Kiyonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KataokaTakahiro en-aut-sei=Kataoka en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency kn-affil= affil-num=5 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency kn-affil= affil-num=9 en-affil=Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency kn-affil= affil-num=10 en-affil=Faculty of Health Sciences, Okayama University kn-affil= affil-num=11 en-affil=Faculty of Health Sciences, Okayama University kn-affil= en-keyword=radon kn-keyword=radon en-keyword=thermal treatment kn-keyword=thermal treatment en-keyword=antioxidant function kn-keyword=antioxidant function en-keyword=oxidative stress kn-keyword=oxidative stress END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=2 article-no= start-page=122 end-page=129 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=RHOA G17V mutation analysis redirecting diagnosis: nodal T-follicular helper cell lymphoma with classic Hodgkin lymphoma feature en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nodal T-follicular helper cell lymphoma (nTFHL) may present with Hodgkin/Reed–Sternberg (HRS)-like cells and can morphologically mimic classic Hodgkin lymphoma (CHL), although these entities are usually distinguishable. We report an unusual case showing marked morphologic and molecular overlap with CHL, creating a diagnostic challenge but ultimately considered biologically consistent with nTFHL.
An 81-year-old woman presented with stage IV disease involving the bone marrow and markedly elevated serum soluble interleukin-2 receptor levels. Excisional lymph node biopsy revealed scattered HRS cells in a T-cell–rich background, with strong CD30 and PD-L1 expression and weak PAX5 positivity, findings consistent with CHL. Fluorescence in situ hybridization demonstrated copy-number alterations at the 9p24.1 locus in HRS cells, further supporting molecular features characteristic of CHL.
However, the presence of two T-follicular helper markers, detection of the RHOA p.Gly17Val (G17V) mutation, and oligoclonal T-cell receptor rearrangements with shared peaks in lymph node and bone marrow indicated an underlying nTFHL. The differential therapeutic response also supported a diagnosis of nTFHL, which could not have been established on morphology alone.
In this case, although the HRS cells displayed morphological, immunophenotypic, and molecular features highly suggestive of CHL, the biological nature of the lesion was consistent with nTFHL. Compared with previously reported cases of nTFHL with HRS-like cells, this case more closely resembled CHL and may represent a distinct subset best described as “nTFHL with CHL features,” a concept warranting greater recognition among pathologists and clinicians. en-copyright= kn-copyright= en-aut-name=YamadaRio en-aut-sei=Yamada en-aut-mei=Rio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukumiTakuya en-aut-sei=Fukumi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhsawaKumiko en-aut-sei=Ohsawa en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MomoseShuji en-aut-sei=Momose en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Department of Hematology, Okayama City Hospital kn-affil= affil-num=5 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=6 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=7 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=classic Hodgkin lymphoma kn-keyword=classic Hodgkin lymphoma en-keyword=nodal T-follicular helper cell lymphoma kn-keyword=nodal T-follicular helper cell lymphoma en-keyword=RHOA mutation kn-keyword=RHOA mutation END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=e77709 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association Between Dinner-to-Bed Time and Gastroesophageal Reflux-Related Diseases in Children en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Gastroesophageal reflux disease (GERD) is characterized by esophageal mucosal injury due to the reflux of gastroduodenal contents. Typical symptoms include heartburn and acid regurgitation. In addition, gastroesophageal reflux (GER) can influence conditions such as otitis media, rhinitis, and asthma. This study aimed to examine the association between dinner-to-bed time and GER-related diseases, such as otitis media, allergic rhinitis, and asthma.
Methods: This was a longitudinal cohort study using secondary data. Data were collected from a large-scale birth cohort study conducted in Japan including babies born in 2001 and 2010. Dinner-to-bed time was categorized as “longer dinner-to-bed time" (>120 minutes), “shorter dinner-to-bed time" (≤120 minutes or less), and “irregular dinner-to-bed time.” Modified Poisson regression with robust variance was used to estimate risk ratios (RRs).
Results: A total of 60,392 children were included in this study. Children with shorter dinner-to-bed time had a higher risk of asthma (adjusted RR (aRR) = 1.10; 95% confidence interval (CI), 1.03-1.18) than those with longer dinner-to-bed time. However, no significant association was observed between shorter dinner-to-bed time and otitis media or allergic rhinitis. Furthermore, supplementary analyses revealed that the risk of asthma was significantly higher in children born in 2001 (aRR = 1.13; 95% CI, 1.04-1.22).
Conclusion: This study showed that dinner-to-bed time within 120 minutes after dinner increases the risk of developing asthma. This underscores the importance of considering lifestyle modifications, as certain pediatric asthma cases may be influenced by behaviors that promote GER. en-copyright= kn-copyright= en-aut-name=UraguchiKensuke en-aut-sei=Uraguchi en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakaoSoshi en-aut-sei=Takao en-aut-mei=Soshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MakiharaSeiichiro en-aut-sei=Makihara en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Otolaryngology- Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=acute otitis media kn-keyword=acute otitis media en-keyword=allergic rhinitis (ar) kn-keyword=allergic rhinitis (ar) en-keyword=gastroesophageal reflux symptoms kn-keyword=gastroesophageal reflux symptoms en-keyword=pediatric asthma kn-keyword=pediatric asthma en-keyword=public health kn-keyword=public health END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=3 article-no= start-page=e80184 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cholecystectomy Is Linked to Worse Clinical Outcomes in Primary Sclerosing Cholangitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent findings have suggested that gallbladder-derived retinoic acid signaling plays a crucial role in the regeneration of damaged intrahepatic biliary ducts. This retrospective cohort study analyzed the clinical records of 20 patients with primary sclerosing cholangitis (PSC) treated at our hospital between 2013 and 2024. We investigated the clinical implications of gallbladder removal in patients with PSC, a progressive cholangiopathy with limited therapeutic options. We retrospectively analyzed the data of patients with PSC and compared patients with and without prior cholecystectomy to assess the impact on disease progression using the Mayo risk score, Fibrosis-4 (FIB4) index, and other clinical parameters. Our findings indicated that cholecystectomy was associated with worse Mayo risk scores (p = 0.0004) and an elevated FIB4 index (p = 0.021), suggesting a potential link between gallbladder removal and accelerated disease progression. Furthermore, mortality and transplant-free survival analysis revealed significantly worse outcomes in the cholecystectomy group (odds ratio = 21.0, p = 0.032). However, given the retrospective nature and small sample size of this study, selection bias cannot be excluded, and further research is needed to confirm these findings. These findings support the hypothesis that gallbladder-derived factors, such as retinoic acid, may influence PSC progression and highlight the need for further research into therapeutic interventions targeting this pathway. en-copyright= kn-copyright= en-aut-name=MiyakeNozomi en-aut-sei=Miyake en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YasugiKengo en-aut-sei=Yasugi en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University kn-affil= en-keyword=biliary diseases kn-keyword=biliary diseases en-keyword=cholecystectomy kn-keyword=cholecystectomy en-keyword=gall bladder kn-keyword=gall bladder en-keyword=liver function kn-keyword=liver function en-keyword=post cholecystectomy kn-keyword=post cholecystectomy en-keyword=primary sclerosing cholangitis (psc) kn-keyword=primary sclerosing cholangitis (psc) END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=10 article-no= start-page=e71325 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vonoprazan-Associated Mucosal Redness: A Report of Two Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vonoprazan, a potassium-competitive acid blocker, is effective at treating acid-related gastrointestinal disorders but has been linked to gastric mucosal redness, a novel condition. This report describes two cases of vonoprazan-associated mucosal redness. Case 1 involved a 73-year-old woman who developed longitudinal erythema and mild mucosal changes after starting vonoprazan seven years ago. Case 2 involved a 70-year-old man who exhibited significant erythema and atrophic gastritis after seven months of treatment. In both cases, the pathological findings included hemorrhage in the superficial mucosa, highlighting that microhemorrhage may be the corresponding pathological finding for vonoprazan-associated mucosal redness. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkedaNobumasa en-aut-sei=Ikeda en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Pathology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Internal Medicine, Clinic Ikeda kn-affil= en-keyword=endoscopy kn-keyword=endoscopy en-keyword=gastric mucosal redness kn-keyword=gastric mucosal redness en-keyword=microhemorrhage kn-keyword=microhemorrhage en-keyword=potassium-competitive acid blocker kn-keyword=potassium-competitive acid blocker en-keyword=vonoprazan kn-keyword=vonoprazan END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=5 article-no= start-page=e84093 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250514 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Influence of Wearing Corsets During Radiation Therapy in Patients With Thoracic or Lumbar Spinal Bone Metastases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
This study aimed to examine the influence of wearing a corset with radiation therapy (RT) on pain, activities of daily living (ADL), and quality of life (QoL) in patients with thoracic or lumbar spinal bone metastases one month after RT.
Methodology
Fifty-two patients (24 males and 28 females) with thoracic or lumbar spinal bone metastases whose measurements were recorded at our institute between July 2012 and December 2016 were included in this study. Age, sex, ADL, pain, spinal instability, and QoL were investigated in our analyses. Patients were divided into stable (0-6 points) and unstable (7-18 points) groups based on their spinal instability neoplastic score. Patients in the stable and unstable groups performed early mobilization depending on their condition. The unstable group wore corsets. The corsets were soft and were worn for three months from the start of RT.
Results
The unstable group showed significant improvements in ADL and QoL and a significant reduction in pain one month after RT (P < 0.05). The stable group showed a significant improvement in QoL one month after RT (P < 0.05).
Conclusions
Corsets were effective for enabling early movement without lowering QoL in patients with spinal instability of thoracic or lumbar bone metastases. en-copyright= kn-copyright= en-aut-name=AkezakiYoshite en-aut-sei=Akezaki en-aut-mei=Yoshite kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KikuuchiMasato en-aut-sei=Kikuuchi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatayamaYoshimi en-aut-sei=Katayama en-aut-mei=Yoshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatayamaHaruyoshi en-aut-sei=Katayama en-aut-mei=Haruyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItanoTakuto en-aut-sei=Itano en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamadaMasanori en-aut-sei=Hamada en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiharaShinsuke en-aut-sei=Sugihara en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Division of Physical Therapy, Kochi Professional University of Rehabilitation kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= en-keyword=activities of daily living kn-keyword=activities of daily living en-keyword=corset kn-keyword=corset en-keyword=pain kn-keyword=pain en-keyword=radiation therapy kn-keyword=radiation therapy en-keyword=spinal bone metastases kn-keyword=spinal bone metastases END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=5 article-no= start-page=e84919 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=Association Between Initial Symptoms and Clinical Outcomes in COVID-19 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The clinical presentation of coronavirus disease 2019 (COVID-19) ranges from localized respiratory symptoms such as cough and sore throat to systemic symptoms such as fever and fatigue. To our knowledge, no study has assessed severe disease risk by dividing onset symptoms into localized respiratory and other symptoms. We aimed to determine whether the risk of severe COVID-19 differs depending on whether the symptoms at onset are limited to local respiratory symptoms.
Method: This was a multicenter prospective cohort study. The patients were classified into localized respiratory or systemic symptom groups based on the symptoms at onset. Demographic data, blood biomarkers, and clinical outcomes, including mortality, intubation, admission to the intensive care unit, and time to discharge, were compared. This study included 100 adult patients diagnosed with COVID-19 between July 2020 and August 2021.
Result: Twelve patients were classified into the localized respiratory symptom group and the remaining 88 into the systemic symptom group. No significant differences between the groups were observed in the baseline characteristics, blood biomarkers, or clinical outcomes. The mortality rates were 0.0% and 4.6%, respectively. The median durations to discharge were 11 and 10 days, respectively (p=0.512). The levels of inflammatory and oxidative stress biomarkers, including interleukin-6 and hydroperoxides, were similar between the groups.
Conclusion: The symptom type at disease onset was not significantly associated with differences in clinical outcomes. Comprehensive assessments beyond initial symptoms are crucial for predicting disease progression and optimizing management strategies. en-copyright= kn-copyright= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki 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=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HasegawaKou en-aut-sei=Hasegawa en-aut-mei=Kou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KudoKenichiro en-aut-sei=Kudo en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanimotoYasushi en-aut-sei=Tanimoto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MitsumuneSho en-aut-sei=Mitsumune en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KimuraGoro en-aut-sei=Kimura en-aut-mei=Goro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamadaHaruto en-aut-sei=Yamada en-aut-mei=Haruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakataIchiro en-aut-sei=Takata en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaniguchiAkihiko en-aut-sei=Taniguchi en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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=16 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=17 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=18 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=19 ORCID= affil-num=1 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, 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 Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=8 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center kn-affil= affil-num=11 en-affil=Department of Infectious Diseases, Okayama City Hospital kn-affil= affil-num=12 en-affil=Department of Internal Medicine, Fukuyama City Hospital 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 Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=15 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Emergency Medicine, Tokyo Metropolitan Institute for Geriatrics and Gerontology kn-affil= affil-num=17 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=clinical outcome kn-keyword=clinical outcome en-keyword=covid-19 kn-keyword=covid-19 en-keyword=localized respiratory symptom kn-keyword=localized respiratory symptom en-keyword=severe disease risk kn-keyword=severe disease risk en-keyword=systemic symptom kn-keyword=systemic symptom 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=8 article-no= start-page=e73170 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Black Hairy Tongue in a 54‐Day‐Old Infant: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Black hairy tongue is a benign condition caused by elongation and defective desquamation of the filiform papillae, and it is uncommon in neonates and infants. We report a case in a 54-day-old girl who presented with a black lesion on the tongue dorsum. The lesion had first been noted at the 1-month medical checkup and persisted despite observation. At presentation, a localized blackish-brown lesion with accentuated filiform papillae was observed on the tongue dorsum and could not be wiped off with gauze. Oral candidiasis was considered in the differential diagnosis, but microbiological examination detected no Candida species. A clinical diagnosis of black hairy tongue was made, and the parents were instructed to gently clean the tongue dorsum with gauze and a sponge brush. The lesion resolved within 2 weeks without recurrence. Recognition of this benign entity may help avoid unnecessary treatment in infants. en-copyright= kn-copyright= en-aut-name=MasuiMasanori en-aut-sei=Masui en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakamotoYumi en-aut-sei=Sakamoto en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=black hairy tongue kn-keyword=black hairy tongue en-keyword=case report kn-keyword=case report en-keyword=infant kn-keyword=infant en-keyword=oral hygiene kn-keyword=oral hygiene END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=1 article-no= start-page=88 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260731 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Early-Stage Oral Squamous Cell Carcinoma in Adolescents and Young Adults Compared with Older Patients Exhibits Distinct Clinicopathological Features en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose This study aimed to compare the clinicopathological features of stage I–II oral squamous cell carcinoma (OSCC) between adolescents and young adults (AYAs) and older patients, and to identify prognostic factors in AYA OSCC.
Methods Forty-eight AYA patients aged 15–39 years and 69 older patients aged ≥ 65 years with surgically treated stage I–II OSCC were retrospectively analyzed. Histological evaluation, survival analysis, immunohistochemistry for p53, p16, and MTAP, high-risk HPV RNA in situ hybridization, and fluorescence in situ hybridization for CDKN2A and MTAP were performed.
Results Compared with older patients, OSCCs in AYAs were more frequently located on the tongue (93.7% vs. 47.8%) and more often exhibited a superficial spreading growth pattern (60.4% vs. 31.8%). AYA tumors more frequently showed modified WPOI-1, high tumor budding, and abnormal p53 immunophenotypes (85.4% vs. 68.1%). AYA patients showed significantly better overall and disease-free survival than older patients. Within the AYA group, depth of invasion (DOI) > 5 mm was associated with distant metastasis and poorer overall and disease-free survival. Postoperative lymph node metastasis occurred in 31.2% of AYAs. Univariable analysis suggested that clinical stage II, tumor thickness > 5 mm, DOI > 5 mm, and tumor budding scores 1–2 were associated with postoperative lymph node metastasis. Molecular status, including p53, p16/CDKN2A, and MTAP, did not provide robust prognostic stratification.
Conclusion Early-stage AYA OSCC exhibits distinct clinicopathological features. DOI was the strongest prognostic indicator, whereas clinical stage, tumor thickness, and tumor budding may provide additional prognostic information regarding the risk of late nodal metastasis. en-copyright= kn-copyright= en-aut-name=OnoSawako en-aut-sei=Ono en-aut-mei=Sawako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiroseKatsutoshi en-aut-sei=Hirose en-aut-mei=Katsutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeTatsuya en-aut-sei=Abe en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MasuiMasanori en-aut-sei=Masui en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkedaChihoko en-aut-sei=Ikeda en-aut-mei=Chihoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IsomuraMadoka en-aut-sei=Isomura en-aut-mei=Madoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TachibanaYuri en-aut-sei=Tachibana en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OnoJunya en-aut-sei=Ono en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShimadaKatsumitsu en-aut-sei=Shimada en-aut-mei=Katsumitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Pathology, Osaka University Graduate School of Dentistry kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology, Osaka Dental University kn-affil= affil-num=8 en-affil=Department of Diagnostic Pathology, School of Medicine, Fujita Health University kn-affil= affil-num=9 en-affil=Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Faculty of Medicine kn-affil= affil-num=10 en-affil=Department of Pathology, The Nippon Dental University School of Life Dentistry at Niigata kn-affil= affil-num=11 en-affil=Department of Clinical Pathophysiology, School of Dentistry, Matsumoto Dental University kn-affil= affil-num=12 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Squamous cell carcinoma of head and neck kn-keyword=Squamous cell carcinoma of head and neck en-keyword=Mouth neoplasms kn-keyword=Mouth neoplasms en-keyword=Adolescent kn-keyword=Adolescent en-keyword=Young adult kn-keyword=Young adult en-keyword=Prognosis kn-keyword=Prognosis en-keyword=Immunohistochemistry kn-keyword=Immunohistochemistry en-keyword=Tumor suppressor protein p53 kn-keyword=Tumor suppressor protein p53 END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=11 article-no= start-page=e73395 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Curve Progression After the Termination of Bracing for Adolescent Idiopathic Scoliosis: Usefulness of Combining the Proximal Femur Maturity Index (PFMI) and Risser Staging en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
The brace therapy for adolescent idiopathic scoliosis (AIS) typically ends upon the end of growth. However, determining the timing of growth cessation can be challenging. The purpose of this study was to evaluate the utility of the proximal femur maturity index (PFMI), which can be assessed simultaneously with Risser staging without requiring additional radiation exposure, in determining the appropriate timing to terminate bracing. To achieve this, we investigated the relationship between skeletal maturity at the end of bracing, post-bracing curve progression, and height growth in patients who had been successfully treated with a brace.
Methods
Between April 2010 and March 2021, a total of 84 female patients with AIS who started bracing at our hospital with an initial Cobb angle of 20-40 degrees were included. All patients were followed for at least one year after brace termination. Height and radiographic parameters (Risser staging, PFMI, Cobb angle) were retrospectively collected.
Results
At the end of the bracing period, patients were categorized into Risser stage 4 (85.7%) and 5 (14.3%). By the last follow-up, patients with Risser stage 4 experienced an average main curve progression of 1.8°, whereas those with Risser stage 5 had an average progression of −0.3° (P = 0.03). Patients with Risser stage 4 were further divided into PFMI grade 5 (59.7%) and 6 (40.3%). Significant curve progression was observed in patients with PFMI grade 5 (average: 3.0°) compared to grade 6 (average: -0.6°) (P < 0.0001). The mean height growth was 1.9 cm/year for PFMI grade 5, and 0.3 cm/year for grade 6, with significant differences between these groups (P < 0.001).
Conclusions
PFMI allowed further categorization within Risser stage 4: PFMI grade 5 indicated remaining growth potential and risk of postbracing curve progression, whereas grade 6 indicated growth cessation. The combined use of Risser staging and PFMI, both evaluable through the same whole-spine radiograph, may provide a more accurate prediction of growth cessation. en-copyright= kn-copyright= en-aut-name=ShitozawaHisakazu en-aut-sei=Shitozawa en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MisawaHaruo en-aut-sei=Misawa en-aut-mei=Haruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TetsunagaTomoko en-aut-sei=Tetsunaga en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShinoharaKensuke en-aut-sei=Shinohara en-aut-mei=Kensuke 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=UedaMasataka en-aut-sei=Ueda en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakatoriRyo en-aut-sei=Takatori en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamashitaKazutaka en-aut-sei=Yamashita en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Ryusou Orthopaedic Hospital kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=adolescent idiopathic scoliosis (ais) kn-keyword=adolescent idiopathic scoliosis (ais) en-keyword=height growth kn-keyword=height growth en-keyword=proximal femur maturity index kn-keyword=proximal femur maturity index en-keyword=risser staging kn-keyword=risser staging en-keyword=skeletal maturation kn-keyword=skeletal maturation END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=11 article-no= start-page=e73778 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241115 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Assessment of All-Inside Sutures to the Posteromedial Capsule in Medial Meniscus Posterior Root Repair: Findings From a Retrospective Three-Dimensional Magnetic Resonance Imaging Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: Medial meniscus (MM) posterior root tears (PRT) cause pathological medial extrusion (MMME) and posterior extrusion (MMPE), particularly during knee flexion, leading to rapidly progressive knee osteoarthritis. We investigated pre- and postoperative MM extrusion using three-dimensional open magnetic resonance imaging (MRI) following two pullout repair techniques: two simple stitches (TSS) and TSS with an additional all-inside suture to the posteromedial capsule (TSS-PM). We hypothesized that TSS-PM would decrease MM extrusion more effectively than TSS.
Methods: Thirty patients who underwent MM posterior root repair were retrospectively evaluated. TSS and TSS-PM techniques were used for pullout repair. Open MRI was performed at 10/90° of knee flexion preoperatively and three months postoperatively. MMME, MMPE, and MM extrusion volume (MMEV) were measured and compared between groups.
Results: At 90° of knee flexion, postoperative MMPE and MMEV were significantly decreased compared to preoperative values in both the TSS and TSS-PM groups. Furthermore, a significantly decreased ΔMMPE was observed in the TSS group compared to the TSS-PM group, whereas no significant difference was observed in ΔMMEV.
Conclusion: TSS and TSS-PM repair techniques helped decrease MMEV at 90° of knee flexion, whereas a significantly decreased ΔMMPE was observed in the TSS group at 90° of knee flexion. An additional all-inside suture at the posteromedial capsule may be insufficient to decrease MMEV and may negatively affect the decrease in ΔMMPE at 90° of knee flexion. en-copyright= kn-copyright= en-aut-name=OkazakiYuki en-aut-sei=Okazaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FurumatsuTakayuki en-aut-sei=Furumatsu en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KintakaKeisuke en-aut-sei=Kintaka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YokoyamaYusuke en-aut-sei=Yokoyama en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TamuraMasanori en-aut-sei=Tamura en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawadaKoki en-aut-sei=Kawada en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HasegawaTsubasa en-aut-sei=Hasegawa en-aut-mei=Tsubasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=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, Japanese Red Cross Okayama Hospital kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=magnetic resonance imaging kn-keyword=magnetic resonance imaging en-keyword=medial meniscus extrusion kn-keyword=medial meniscus extrusion en-keyword=posterior root tear kn-keyword=posterior root tear en-keyword=pullout repair technique kn-keyword=pullout repair technique en-keyword=three-dimensional reconstruction kn-keyword=three-dimensional reconstruction END start-ver=1.4 cd-journal=joma no-vol=229 cd-vols= no-issue= article-no= start-page=105080 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enhanced calcium activity and transcriptomic alterations in iPSC-derived neurons from BAFME patients with repeat expansions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Benign adult familial myoclonus epilepsy (BAFME) is caused by intronic TTTCA and TTTTA repeat expansions in SAMD12 and other genes; the neuronal basis of cortical hyperexcitability, however, remains unclear. We generated induced pluripotent stem cell (iPSC)-derived glutamatergic and GABAergic neurons from three BAFME1 patients and examined functional and transcriptomic phenotypes. Patient-derived neurons retained the pathogenic repeat expansions and showed a tendency toward upstream intronic RNA accumulation. Calcium imaging revealed increased spontaneous Ca2 + transient frequency in both neuronal subtypes, indicating heightened activity. Pharmacological profiling demonstrated attenuated responses to calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor (CP-AMPAR) blockade and GABAA receptor antagonism in GABAergic neurons, suggesting altered inhibitory signaling. RNA sequencing revealed transcriptomic alterations without differential expression of ion channels and neurotransmitter receptors. In glutamatergic neurons, ATF4-regulated genes, including SLC7A5 encoding LAT1, a Kv1.2 channel modulator, were downregulated. Reduced SLC7A5 expression was validated at both mRNA and protein levels. In GABAergic neurons, synapse-associated genes PTPRD and GPC6 were upregulated. TCERG1L and NLRP2 were suppressed across both neuronal subtypes. These findings suggest subtype-specific alterations may contribute to neuronal hyperexcitability in BAFME and provide a platform for mechanistic studies of repeat expansion-associated epilepsies. en-copyright= kn-copyright= en-aut-name=NagasakoYuki en-aut-sei=Nagasako en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshikawaMitsuru en-aut-sei=Ishikawa en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SupakulSopak en-aut-sei=Supakul en-aut-mei=Sopak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaedaSumihiro en-aut-sei=Maeda en-aut-mei=Sumihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkanoHideyuki en-aut-sei=Okano en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Physiology, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Physiology, Keio University School of Medicine kn-affil= affil-num=5 en-affil=Department of Physiology, Keio University School of Medicine kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Physiology, Keio University School of Medicine kn-affil= en-keyword=Induced pluripotent stem cells kn-keyword=Induced pluripotent stem cells en-keyword=Glutamatergic neurons kn-keyword=Glutamatergic neurons en-keyword=GABAergic neurons kn-keyword=GABAergic neurons en-keyword=Calcium imaging kn-keyword=Calcium imaging en-keyword=BAFME kn-keyword=BAFME en-keyword=Repeat expansion kn-keyword=Repeat expansion en-keyword=Epilepsy kn-keyword=Epilepsy END start-ver=1.4 cd-journal=joma no-vol=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=83 cd-vols= no-issue=10 article-no= start-page=565 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260730 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Osmotic pressure, correlation lengths and viscosity of aqueous pullulan solutions beyond the overlap concentration en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigate the thermodynamic, scattering, and flow properties of pullulan, a flexible non-ionic polysaccharide in aqueous solution, focusing on semidilute and concentrated solutions. We review dilute solution data for the intrinsic viscosity and radius of gyration and hydrodynamic radius of aqueous pullulan and find the Kuhn length and thermal blob size, below which the polymer chain is nearly ideal, to be 3 nm and 20 nm, respectively. We establish the scaling laws for static correlation length, specific viscosity, osmotic pressure, and osmotic compressibility across dilute, semidilute, and concentrated regions, finding that the scaling exponents align well with theoretical predictions but the crossover concentrations obtained from different methods are not consistent. The ratio between the osmotic and Ornstein–Zernike correlation lengths ξΠ/ξOZ is approximately 2.5 for aqueous solutions, similar to that observed in polystyrene in a theta solvent. This similarity may arise because the crossover concentration between the semidilute and concentrated regions c∗∗ is close to the overlap concentration c∗. en-copyright= kn-copyright= en-aut-name=MengLingzi en-aut-sei=Meng en-aut-mei=Lingzi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwatoRene en-aut-sei=Iwato en-aut-mei=Rene kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeTakaichi en-aut-sei=Watanabe en-aut-mei=Takaichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LopezCarlos G. en-aut-sei=Lopez en-aut-mei=Carlos G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Materials Science and Engineering, The Pennsylvania State University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Materials Science and Engineering, The Pennsylvania State University kn-affil= en-keyword=Pullulan kn-keyword=Pullulan en-keyword=Osmotic pressure kn-keyword=Osmotic pressure en-keyword=Correlation length kn-keyword=Correlation length en-keyword=Semidilute solutions kn-keyword=Semidilute solutions en-keyword=Concentrated solutions kn-keyword=Concentrated solutions en-keyword=Viscosity kn-keyword=Viscosity en-keyword=SAXS kn-keyword=SAXS en-keyword=SANS kn-keyword=SANS en-keyword=DLS kn-keyword=DLS END start-ver=1.4 cd-journal=joma no-vol=541 cd-vols= no-issue= article-no= start-page=113868 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of a novel histidine-rich glycoprotein measurement system as a biomarker for sepsis en-subtitle= kn-subtitle= en-abstract= kn-abstract=The plasma histidine-rich glycoprotein concentration is a marker of sepsis severity. In this study, we generated selective and specific monoclonal antibodies against histidine-rich glycoprotein for use in a prototype enzyme-linked immunosorbent assay-based in vitro diagnostic system. First, we investigated the properties of monoclonal antibodies produced by 21 hybridomas that we developed using immunized mice, and we identified monoclonal antibodies 69-1A and 75-2D to be the most suitable combination for use in the sandwich enzyme-linked immunosorbent assay. Wild-type histidine-rich glycoprotein (Form-1, 75 kDa) with a proline residue at amino acid position 204 is the most common isoform of the protein in humans, followed by its variant (Form-2, 77 kDa), which has a serine residue at position 204.
The epitope mapping was examined for the HRG amino acid sequence with 69-1A and 75-2D mAbs to achieve the identification of respective specific binding domains, though the other kinds of mAbs showed considerably complex domains. The identified epitopes recognized by 69-1A and 75-2D monoclonal antibodies did not span position 204. Furthermore, immunoprecipitation-immunoblotting analysis showed that the 69-1A and 75-2D monoclonal antibodies could bind to both Form-1 and Form-2 in human plasma samples. Thus, these two new antibodies can be used to clearly detect both forms of histidine-rich glycoproteins in human plasma samples. In our analysis of clinical samples by enzyme-linked immunosorbent assays using various combinations of our newly synthesized antibodies, we found that the histidine-rich glycoprotein concentration was significantly lower in plasma samples from septic patients than in those from healthy volunteers (p < 0.01). Thus, our novel analysis system using the new antibodies is expected to be a useful tool for sepsis research, and it may be adapted as an in vitro diagnostic tool for many other kinds of diseases in the future. en-copyright= kn-copyright= en-aut-name=UchiumiTakaoki en-aut-sei=Uchiumi en-aut-mei=Takaoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueYoko en-aut-sei=Inoue en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiHiroshi en-aut-sei=Nishi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtaNorio en-aut-sei=Ota en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Diagnostic Drug Office, Shionogi & Co., Ltd. kn-affil= affil-num=2 en-affil=Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Diagnostic Drug Office, Shionogi & Co., Ltd. kn-affil= affil-num=5 en-affil=Diagnostic Drug Office, Shionogi & Co., Ltd. kn-affil= affil-num=6 en-affil=Diagnostic Drug Office, Shionogi & Co., Ltd. kn-affil= en-keyword=Histidine-rich glycoprotein kn-keyword=Histidine-rich glycoprotein en-keyword=Sandwich enzyme-linked immunosorbent assay kn-keyword=Sandwich enzyme-linked immunosorbent assay en-keyword=In vitro diagnostics kn-keyword=In vitro diagnostics en-keyword=Sepsis kn-keyword=Sepsis en-keyword=Anti-human histidine-rich glycoprotein mouse monoclonal antibody kn-keyword=Anti-human histidine-rich glycoprotein mouse monoclonal antibody END start-ver=1.4 cd-journal=joma no-vol=542-543 cd-vols= no-issue= article-no= start-page=108716 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20261115 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Serpentinization parageneses controlled by lithological variations among olivine gabbro and peridotite from the Atlantis Massif, Mid-Atlantic Ridge en-subtitle= kn-subtitle= en-abstract= kn-abstract=Serpentinization of olivine impacts the geochemical and ecological environment via molecular hydrogen production, promoted by iron oxidation to form magnetite and ferric iron in serpentine. Previous studies suggested that serpentinization proceeds with various reactions and the extent of iron oxidation is variable depending on the reaction pathways. To examine the effect of lithological variation on reactions at an incipient stage of serpentinization, we carried out microscopic observations, electron-probe analyses, and Raman spectroscopy of serpentine veins cutting olivine in gabbroic rocks and peridotites from the Atlantis Massif, Mid-Atlantic Ridge. The results indicate that the serpentine veins in the proximity of olivine dominantly comprise lizardite mixed with variable minor phases or components depending on igneous lithology: brucite in peridotites, troctolites, and primitive olivine gabbros; cronstedtite-bearing serpentine, commonly without brucite, in some troctolites and slightly evolved olivine gabbros; and neither brucite nor cronstedtite component in evolved olivine gabbros. This suggests that incipient-stage serpentinization paragenesis is dominantly controlled by silica activity reflecting lithological variation. In addition to magnetite, the formation of cronstedtite in gabbroic rocks has the potential to produce hydrogen. The presence or absence of brucite and cronstedtite could affect the timing and magnitude of iron oxidation and hydrogen production during serpentinization. Considering the predominance of gabbroic rocks in the lower oceanic crust, the variation in incipient-stage serpentinization paragenesis in gabbroic rocks may have an impact on the redox state and ecological environment around the (sub)seafloor. en-copyright= kn-copyright= en-aut-name=NozakaToshio en-aut-sei=Nozaka en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KazumataShun en-aut-sei=Kazumata en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KleinFrieder en-aut-sei=Klein en-aut-mei=Frieder kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Marine Chemistry and Geochemistry, Woods Hole Oceanographic Institution kn-affil= en-keyword=Serpentinization kn-keyword=Serpentinization en-keyword=Brucite kn-keyword=Brucite en-keyword=Cronstedtite kn-keyword=Cronstedtite en-keyword=Olivine gabbro kn-keyword=Olivine gabbro en-keyword=Peridotite kn-keyword=Peridotite en-keyword=Atlantis Massif kn-keyword=Atlantis Massif END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260722 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dissociation between globe shape-induced rectus muscle pulley displacement and abduction limitation in patients aged 40 years and older with high myopic strabismus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose We hypothesized that high myopia (HM)-induced globe deformation displaces rectus muscle (RM) pulleys, contributing to mild ocular motility restriction. This study investigated the effects of globe shape on RM pulley positions in older Japanese patients with acquired strabismus (AS) and mild motility restriction—defined as the ability to abduct both eyes beyond the midline.
Methods In this retrospective case series, 28 patients (mean age ± standard deviation: 61.2 ± 9.0 years) with adult-onset AS were included: 6 patients with (LAB group) and 22 patients without abduction limitation (NLAB group). In each subject, the eye with the longer axial length (AL ≥ 26 mm), measured using an AL measurement apparatus, was analyzed using magnetic resonance imaging (MRI). RM pulley positions relative to the globe center and equatorial diameter (ED) were measured; the ED-to-AL ratio (EAR) was calculated. We compared these parameters between groups and analyzed correlations of globe-shape factors (EAR, AL, and ED) with pulley positions and age.
Results No significant differences in EAR, AL, ED, or pulley positions were detected between LAB and NLAB groups, possibly owing to the limited sample size and group imbalance, in the analyzed eyes. However, as EAR decreased (prolate deformation), the superior rectus (SR) pulley (r = 0.68, P < 0.01) and inferior rectus (IR) pulley (r = 0.40, P = 0.03) significantly displaced nasally. AL (r = -0.52, P < 0.01) correlated with the horizontal SR pulley position. Furthermore, age significantly correlated with AL (r = 0.45, P = 0.02) and decrease in EAR (r = -0.41, P = 0.03).
Conclusions In older Japanese patients with HM and AS, prolate globe deformation was associated with age and significantly correlated with SR and IR pulley positions. While the direct relationship between these structural changes and the clinical degree of mild abduction limitation requires further investigation in larger cohorts, EAR sensitively reflected age-related morphological shifts; thus, when used in conjunction with AL, EAR may represent a readily measurable MRI-based parameter associated with restrictive motility tendencies in strabismus with high myopia. en-copyright= kn-copyright= en-aut-name=KonoReika en-aut-sei=Kono en-aut-mei=Reika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamasakiIchiro en-aut-sei=Hamasaki en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KishimotoFumiko en-aut-sei=Kishimoto en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShibataKiyo en-aut-sei=Shibata en-aut-mei=Kiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MorisawaShin en-aut-sei=Morisawa en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Lino Eye Clinic kn-affil= affil-num=3 en-affil=Division of Ophthalmology, Ibara City Hospital kn-affil= affil-num=4 en-affil=Lino Eye Clinic kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Heavy eye syndrome kn-keyword=Heavy eye syndrome en-keyword=High myopia kn-keyword=High myopia en-keyword=Magnetic resonance imaging kn-keyword=Magnetic resonance imaging en-keyword=Prolate deformation kn-keyword=Prolate deformation en-keyword=Rectus muscle pulley kn-keyword=Rectus muscle pulley en-keyword=Strabismus kn-keyword=Strabismus END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=7 article-no= start-page=e73156 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=Custom‐Made Mouthpiece‐Assisted Oral Cryotherapy During Hematopoietic Stem Cell Transplantation in a Patient With Hemimaxillectomy‐Related Oroantral Communication: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=A custom-made mouthpiece enabled safe oral cryotherapy in a patient with extensive oroantral communication after hemimaxillectomy and may also be applicable to other patients with communication between the oral cavity and the maxillary sinus or nasal cavity. en-copyright= kn-copyright= en-aut-name=MatsuzakiKumiko en-aut-sei=Matsuzaki en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiFuminobu en-aut-sei=Miyazaki en-aut-mei=Fuminobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotoyamaYasuji en-aut-sei=Motoyama en-aut-mei=Yasuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakedaSeiko en-aut-sei=Takeda en-aut-mei=Seiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=SogaYoshihiko en-aut-sei=Soga en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Dental Laboratory Division, Okayama University Hospital kn-affil= affil-num=3 en-affil=Dental Laboratory Division, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Dental Laboratory Division, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= en-keyword=hematopoietic stem cell transplantation kn-keyword=hematopoietic stem cell transplantation en-keyword=hemimaxillectomy kn-keyword=hemimaxillectomy en-keyword=mouthpiece kn-keyword=mouthpiece en-keyword=oral cryotherapy kn-keyword=oral cryotherapy en-keyword=oral mucositis kn-keyword=oral mucositis END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=6 article-no= start-page=103486 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Students’ perceptions of an electronic one-minute paper in a radiography training programme: An exploratory cross-sectional questionnaire study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Formative assessment can support health professions education; however, reports on electronic 1-min papers as classroom feedback and engagement tools in radiography programmes remain limited. This study explored radiography students’ perceptions of an electronic 1-min paper, focusing on in-class reflection, ease of asking questions, and instructor feedback.
Methods: An electronic 1-min paper was used in a radiotherapy course across 45 class sessions in the 2024 academic year for third-year students enrolled in a 4-year radiography programme. Each 90-min class comprised a 60-min lecture, 10-min completion of the paper, and 20-min instructor feedback. After the course, a de-identified online questionnaire was administered. Eleven 5-point Likert-scale items were analysed using descriptive statistics and Spearman's rank correlations. Free-text responses were analysed using inductive qualitative content analysis.
Results: Of the 77 eligible students, 74 responded (96.1%). Ease of use received the highest rating (mean, 4.76; standard deviation [SD], 0.52), followed by ease of asking questions (mean, 4.32), question resolution (mean, 4.16), and usefulness of instructor feedback (mean, 4.08). Motivation to review after class was lowest (mean, 3.04; SD, 1.16). Active participation showed a strong positive association with in-class concentration (rs = 0.815; P < 0.001). Free-text responses indicated reflection and improved understanding, anonymous sharing of questions, active listening and concentration, and suggestions for improvement.
Conclusion: The electronic 1-min paper was widely accepted and perceived to support in-class reflection, question expression, and immediate feedback. However, students’ perceptions of its influence on out-of-class review motivation were limited. The findings indicate perceived value and engagement rather than demonstrated educational effectiveness.
Implications for practice: Electronic 1-min papers may help instructors identify students’ questions and respond during class, providing a practical approach to in-class feedback. en-copyright= kn-copyright= en-aut-name=KomatsuY. en-aut-sei=Komatsu en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AbeS. en-aut-sei=Abe en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsudouS. en-aut-sei=Tsudou en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoY. en-aut-sei=Yamamoto en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanabeY. en-aut-sei=Tanabe en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Faculty of Health Care Sciences, Jikei University of Health Care Sciences kn-affil= affil-num=3 en-affil=Department of Radiological Technology, Faculty of Health Care Sciences, Jikei University of Health Care Sciences kn-affil= affil-num=4 en-affil=Division of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Health Sciences, Department of Radiological Technology, Okayama University Medical School, Okayama University kn-affil= en-keyword=Electronic 1-min paper kn-keyword=Electronic 1-min paper en-keyword=Formative assessment kn-keyword=Formative assessment en-keyword=Radiography education kn-keyword=Radiography education en-keyword=Immediate feedback kn-keyword=Immediate feedback en-keyword=Student engagement kn-keyword=Student engagement en-keyword=Health professions education kn-keyword=Health professions education END start-ver=1.4 cd-journal=joma no-vol=34 cd-vols= no-issue=8 article-no= start-page=747 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260709 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Incidence and impact of odontogenic infection-related febrile episodes during perioperative doxorubicin-cyclophosphamide or docetaxel-cyclophosphamide chemotherapy for breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Doxorubicin-cyclophosphamide (AC) and docetaxel-cyclophosphamide (TC) are standard perioperative chemotherapy regimens for breast cancer. Febrile neutropenia (FN) is a common adverse event, and odontogenic infections may contribute to febrile episodes. This study was performed to investigate the incidence and impact of febrile episodes clinically associated with odontogenic infections during AC and TC chemotherapy.
Methods A total of 408 patients with breast cancer receiving 4 cycles of AC (n = 285) or TC (n = 123) between 2015 and 2020 were included in this single-center retrospective study. Patients recorded daily axillary temperatures and oral symptoms. Dental evaluations were performed when oral infection was suspected. Febrile episodes (≥ 37.5 °C) were assessed, and their clinical association with odontogenic infections was determined based on dental records and the documented clinical course. Relative dose intensity (RDI) was calculated to assess chemotherapy delivery.
Results Overall, 40.2% of patients experienced febrile episodes, and the frequency was higher in the TC group (48.8%) than the AC group (36.5%, P = 0.02). Febrile episodes associated with oral infections occurred in 9.1% of patients, of which 78.4% were clinically associated with odontogenic infections (7.1% of all patients). Most such episodes occurred during the first chemotherapy cycle (79.3%, P < 0.01). Chemotherapy RDI was reduced in three patients with febrile episodes clinically associated with odontogenic infection, but remained ≥ 85%.
Conclusions Febrile episodes clinically associated with odontogenic infections occurred in approximately 7%–8% of patients with breast cancer receiving perioperative AC or TC chemotherapy, predominantly during the first cycle. Odontogenic infections should be considered one possible source of febrile episodes during treatment. en-copyright= kn-copyright= en-aut-name=SogaYoshihiko en-aut-sei=Soga en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuzakiKumiko en-aut-sei=Matsuzaki en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KosakiHirotaka en-aut-sei=Kosaki en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KishimotoTomoko en-aut-sei=Kishimoto en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshitomiAiko en-aut-sei=Yoshitomi en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KajizonoMakoto en-aut-sei=Kajizono en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MakitaTakashi en-aut-sei=Makita en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaYuta en-aut-sei=Tanaka en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Division of Hospital Dentistry, 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 Pharmacy, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Surgery, Kawasaki Medical School General Medical Center kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Perioperative chemotherapy kn-keyword=Perioperative chemotherapy en-keyword=Odontogenic infection kn-keyword=Odontogenic infection en-keyword=Oral infection kn-keyword=Oral infection en-keyword=Febrile episodes kn-keyword=Febrile episodes en-keyword=Relative dose intensity kn-keyword=Relative dose intensity 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 < 0.001), although the C-statistic change was not significant (from 0.724 to 0.725, p = 0.835).
Conclusions: CAVI is independently associated with significant coronary stenosis in MASLD patients and may serve as a non-invasive screening tool to enhance cardiovascular risk stratification. Its moderate diagnostic accuracy suggests utility as a component of a multifactorial risk assessment strategy. en-copyright= kn-copyright= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UekiYuta en-aut-sei=Ueki en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishiharaTakahiro en-aut-sei=Nishihara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MikiTakashi en-aut-sei=Miki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaraShohei en-aut-sei=Hara en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IchikawaKeishi en-aut-sei=Ichikawa en-aut-mei=Keishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OsawaKazuhiro en-aut-sei=Osawa en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School General Medicine Centre kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Cardio-ankle vascular index kn-keyword=Cardio-ankle vascular index en-keyword=Steatotic liver kn-keyword=Steatotic liver en-keyword=Coronary artery disease kn-keyword=Coronary artery disease en-keyword=Arterial stiffness kn-keyword=Arterial stiffness en-keyword=Screening kn-keyword=Screening END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=19 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Plasma expression levels of microRNA-101 are downregulated in patients with Parkinson’s disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons. Endoplasmic reticulum (ER) stress contributes to PD pathogenesis, with the ER-associated degradation (ERAD) system playing a protective role. HRD1, an ER-resident ubiquitin ligase, and its stabilizer SEL1L are involved in ERAD and neuronal survival. This study investigated alterations in the plasma levels of microRNA-101 (miR-101), which targets SEL1L, in patients with PD, and its potential role as a biomarker.
Results Plasma miR-101 levels in patients with PD significantly decreased compared with those in healthy controls. Receiver operating characteristic curve analysis demonstrated that miR-101 could moderately discriminate patients with PD from healthy individuals (area under the curve = 0.781, 95% confidence interval = 0.547–1.00). The optimal cutoff, as determined by the Youden index, was 0.737 (expression ratio relative to that in the healthy control group), yielding a sensitivity of 50% and specificity of 100%. These results suggested that reduced plasma miR-101 expression may reflect the pathophysiological state of PD, and miR-101 has potential as minimally invasive biomarker for PD. en-copyright= kn-copyright= en-aut-name=OmuraTomohiro en-aut-sei=Omura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiguchiHiroki en-aut-sei=Nishiguchi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanedaHaruka en-aut-sei=Kaneda en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitahiroYumi en-aut-sei=Kitahiro en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItoharaKotaro en-aut-sei=Itohara en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakaneToshiyasu en-aut-sei=Sakane en-aut-mei=Toshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YanoIkuko en-aut-sei=Yano en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=2 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=3 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=4 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=5 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=6 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pharmaceutical Technology, Kobe Pharmaceutical University kn-affil= affil-num=8 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= en-keyword=Parkinson’s disease kn-keyword=Parkinson’s disease en-keyword=microRNA kn-keyword=microRNA en-keyword=Endoplasmic reticulum stress kn-keyword=Endoplasmic reticulum stress en-keyword=HRD1 kn-keyword=HRD1 en-keyword=SEL1L kn-keyword=SEL1L END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260707 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sex differences and contest experience shape walking patterns in the broad-horned flour beetle en-subtitle= kn-subtitle= en-abstract= kn-abstract=Animal movement patterns vary widely across species, and sex differences are often expected because males typically need to encounter multiple females and acquire resources. In species where males engage in male–male combat using exaggerated weapons, variation in weapon size and contest outcomes is known to influence male reproductive strategies, and may therefore also affect movement behavior. However, sex-specific and male-specific differences in locomotor behavior, particularly in relation to weapon size and social interactions, remain poorly understood. Here, we investigated walking trajectories in the broad-horned flour beetle (Gnatocerus cornutus) to test for (1) sex differences, (2) associations between male weapon size and movement behavior, and (3) the effects of male–male combat. Males exhibited more tortuous and localized movement, whereas females showed straighter and more spatially extensive trajectories. Following contests, all males showed a reduction in activity regardless of contest outcome; however, winners and losers exhibited divergent changes in movement patterns, with winners showing straighter and more spatially extensive trajectories and losers showing more tortuous and localized trajectories. In contrast, body-size-corrected weapon size was not associated with any aspect of walking behavior. These results indicate that locomotor behavior in G. cornutus varies with sex and contest experience, and that variation in walking behavior is more closely associated with social experience than with weapon morphology. en-copyright= kn-copyright= en-aut-name=MatsumuraKentarou en-aut-sei=Matsumura en-aut-mei=Kentarou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HashiokaSora en-aut-sei=Hashioka en-aut-mei=Sora kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagayaNaohisa en-aut-sei=Nagaya en-aut-mei=Naohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujisawaRyusuke en-aut-sei=Fujisawa en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyatakeTakahisa en-aut-sei=Miyatake en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Arts and Sciences, The University of Tokyo kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Information Science and Engineering, Kyoto Sangyo University kn-affil= affil-num=4 en-affil=Faculty of Environmental Engineering, University of Kitakyushu, kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Turning angle kn-keyword=Turning angle en-keyword= Acceleration kn-keyword= Acceleration en-keyword=Male-male combat kn-keyword=Male-male combat en-keyword=Weapon kn-keyword=Weapon en-keyword=ANTAM kn-keyword=ANTAM END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=8 article-no= start-page=1172 end-page=1177 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=Autopsy Case of a Disseminated Cytomegalovirus Infection with a Cutaneous Ulcer Mimicking Rheumatoid Vasculitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 60-year-old woman with rheumatoid arthritis and an impaired consciousness was referred to our hospital. Prior to transfer, the patient underwent intensified immunosuppressive therapy under a diagnosis of rheumatoid vasculitis that had developed in her buttocks. Upon hospitalization, she developed severe multiorgan failure and hemophagocytic syndrome. Four days after admission, both blood cytomegalovirus (CMV) antigenemia and the DNA load were markedly elevated. Despite intensive care, the patient died. Later, a histopathological examination revealed that the cutaneous manifestation represented CMV disease, not rheumatoid vasculitis, as was initially suspected. Failure to identify CMV as the underlying cause may result in the inappropriate administration of immunosuppressive therapy, potentially worsening the patient's condition. en-copyright= kn-copyright= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoYukichika en-aut-sei=Yamamoto en-aut-mei=Yukichika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshidaTomoharu en-aut-sei=Ishida en-aut-mei=Tomoharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhkiTomoka en-aut-sei=Ohki en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of 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 Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=autopsy kn-keyword=autopsy en-keyword=cytomegalovirus kn-keyword=cytomegalovirus en-keyword=cutaneous cytomegalovirus kn-keyword=cutaneous cytomegalovirus en-keyword=virus-associated hemophagocytic syndrome kn-keyword=virus-associated hemophagocytic syndrome en-keyword=rheumatoid vasculitis kn-keyword=rheumatoid vasculitis END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=7 article-no= start-page=1069 end-page=1073 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=Nasal Mucosal Manifestation of Behçet's Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Behçet's disease (BD) is a multisystem inflammatory condition that rarely affects the nasal mucosa. We report the case of a 25-year-old man presenting with prolonged fever, bilateral rhinalgia, and nasal obstruction, who was subsequently diagnosed with nasal ulcers associated with BD. These ulcers resolved along with the systemic symptoms following treatment with colchicine, apremilast, and prednisolone. Although there is no specific treatment strategy for nasal mucosal lesions in BD, standard systemic therapies may be effective. This case highlights nasal mucosal involvement as a rare but important manifestation of BD, emphasizing the importance of thorough evaluation and consideration of nasal symptoms for the diagnosis and treatment. en-copyright= kn-copyright= en-aut-name=AkiyamaHiroshi en-aut-sei=Akiyama en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 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=5 ORCID= en-aut-name=KatayamaYu en-aut-sei=Katayama en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoAki en-aut-sei=Sato en-aut-mei=Aki 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= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of 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 Nephrology, Rheumatology, Endocrinology and Metabolism, 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 Science kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Behçet's disease kn-keyword=Behçet's disease en-keyword=nasal mucosal manifestation kn-keyword=nasal mucosal manifestation en-keyword=apremilast kn-keyword=apremilast en-keyword=colchicine kn-keyword=colchicine en-keyword=prednisolone kn-keyword=prednisolone END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=3 article-no= start-page=107 end-page=115 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260315 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Full-endoscopic Laminotomy Is Effective for Lumbar Spinal Stenosis with Low-grade Spondylolisthesis: A Comparative Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The optimal management of lumbar spinal canal stenosis with spondylolisthesremains controversial, particularly when choosing between decompression alone or decompression with fusion. Current evidence is based on conventional open or endoscopy-assisted surgeries, with limited data on full-endoscopic decompression. This study aimed to assess the impact of spondylolisthesis on outcomes after full-endoscopic laminotomy by evaluating back pain-related disability scores in patients with lumbar spinal canal stenosis, with and without spondylolisthesis. A retrospective analysis was conducted at Iwai Orthopaedic Hospital, Japan. Patients with lumbar spinal canal stenosis who underwent full-endoscopic laminotomy between January 2021 and December 2022 were included and categorized into those without spondylolisthesis and those with spondylolisthesis. Postoperative Oswestry Disability Index scores at 2 years were compared in the groups using multivariable linear regression, adjusting for confounding factors. Exploratory analyses were also conducted to identify factors affecting the Oswestry Disability Index in the patients with lumbar spinal canal stenosis with spondylolisthesis group. Statistical significance was set at p < 0.05. The study included 80 patients, with 40 in each group. Both groups showed improved postoperative Oswestry Disability Index. There was no significant association between spondylolisthesis and postoperative Oswestry Disability Index. However, cauda equina redundancy negatively affected postoperative Oswestry Disability Index improvement in the patients with lumbar spinal canal stenosis with spondylolisthesis group. Full-endoscopic laminotomy is an effective surgical option for lumbar spinal canal stenosis, leading to significant alleviation of disability and improvements in quality of life, regardless of spondylolisthesis. Full-endoscopic laminotomy may offer similar functional improvements regardless of the presence of low-grade spondylolisthesis, supporting its role as a less invasive alternative to fusion. en-copyright= kn-copyright= en-aut-name=KINKyohei en-aut-sei=KIN en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TOMINAGARyoji en-aut-sei=TOMINAGA en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TAKEBAYASHIKento en-aut-sei=TAKEBAYASHI en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IWAIHiroki en-aut-sei=IWAI en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=INANAMIHirohiko en-aut-sei=INANAMI en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KOGAHisashi en-aut-sei=KOGA en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopaedics, Iwai Orthopaedic Medical Hospital kn-affil= affil-num=3 en-affil=Department of Orthopaedics, Iwai Orthopaedic Medical Hospital kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedics, Iwai Orthopaedic Medical Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedics, Iwai Orthopaedic Medical Hospital kn-affil= en-keyword=full-endoscopic spine surgery kn-keyword=full-endoscopic spine surgery en-keyword=spondylolisthesis kn-keyword=spondylolisthesis en-keyword=full-endoscopic laminotomy kn-keyword=full-endoscopic laminotomy en-keyword=minimally invasive kn-keyword=minimally invasive en-keyword=lumbar spinal canal stenosis kn-keyword=lumbar spinal canal stenosis END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=5 article-no= start-page=823 end-page=827 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Global trends in sarcoidosis-associated mortality, 2001–2023: insights from the World Health Organization mortality database en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HaradaKo en-aut-sei=Harada en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiMariko en-aut-sei=Fujii en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakoNanami en-aut-sei=Sako en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=VuQuynh Thi en-aut-sei=Vu en-aut-mei=Quynh Thi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BelangoyKeith Pardillada en-aut-sei=Belangoy en-aut-mei=Keith Pardillada kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OuddoudHanane en-aut-sei=Ouddoud en-aut-mei=Hanane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=2 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Division of Hematology and Oncology, Mayo Clinic kn-affil= affil-num=6 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Education and Research Centre for Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue= article-no= start-page=105422 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pathological features of residual head and neck cancer after near-infrared photoimmunotherapy: implications of an unfavorable tumor immune microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: Near-infrared photoimmunotherapy has been approved in Japan for unresectable locally advanced or recurrent head and neck cancer. While this therapy theoretically induces selective necrosis of epidermal growth factor receptor-expressing tumor cells following administration of cetuximab sarotalocan sodium and irradiation with 690-nm light, residual disease is not uncommon in clinical practice. The mechanisms underlying such persistence remain poorly understood.
Methods: We examined two patients with head and neck squamous cell carcinoma who underwent salvage resection due to residual disease after four cycles of near-infrared photoimmunotherapy. Resected specimens were subjected to histopathological evaluation, including immunohistochemistry for epidermal growth factor receptor, cluster of differentiation 8, programmed cell death protein 1, and forkhead box P3 proteins.
Results: In both cases, residual tumor cells were predominantly localized in the superficial mucosal layers, while deeper layers were replaced by fibrosis. All residual tumors retained expression of epidermal growth factor receptor. Lymphocytic infiltration was sparse, with scattered cluster of differentiation 8-positive cells but few programmed cell death protein 1-positive or forkhead box P3-positive lymphocytes. These findings suggest that the tumor microenvironment surrounding residual tumors may have been unfavorable for the induction of robust antitumor immune responses.
Conclusion: Residual tumors after near-infrared photoimmunotherapy can occur despite adequate laser irradiation and epidermal growth factor receptor expression. Our observations imply that insufficient immune activation within the tumor microenvironment may contribute to treatment resistance. Further characterization of the post-photoimmunotherapy tumor microenvironment will be essential to better understand treatment mechanisms and to optimize therapeutic efficacy. en-copyright= kn-copyright= en-aut-name=MakinoTakuma en-aut-sei=Makino en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaoiYuto en-aut-sei=Naoi en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=NIR-PIT kn-keyword=NIR-PIT en-keyword=EGFR kn-keyword=EGFR en-keyword=CD8 kn-keyword=CD8 en-keyword=PD-1 kn-keyword=PD-1 en-keyword=FOXP3 kn-keyword=FOXP3 en-keyword=Tumor microenvironment kn-keyword=Tumor microenvironment en-keyword=Photoimmunotherapy kn-keyword=Photoimmunotherapy en-keyword=Head and neck cancer kn-keyword=Head and neck cancer END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=16760 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260409 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Asthma-like bronchodilator responsiveness in patients with neuronal intranuclear inclusion disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative condition characterized by the presence of intranuclear inclusions in neuronal and visceral cells. Patients with NIID can present respiratory symptoms; however, data on pulmonary functions in NIID are lacking. This study investigated the respiratory conditions in NIID patients diagnosed with histopathological and genetic studies. We conducted two spirometries before and after administrating the bronchodilator in NIID patients with asthmatic histories or symptoms. We statistically compared pre- and post-measured values including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF). Before two spirometries, we also measured fractional concentration of exhaled nitric oxide (FeNO), if possible. Of the 51finally enrolled patients, 17 (33.3%, 95% CI 20.8% to 47.9%) patients had asthmatic histories or symptoms, and 14 patients received two spirometries. After administrating the bronchodilator, FEV1 and PEF significantly increased by 150 mL (6.01%, p = 0.002) and 260 mL/s (6.72%, p = 0.017), respectively. The median (interquartile range) of FeNO measured in nine patients was 15 (10–21) ppb. Patients with NIID have airflow reversibility like asthma. This condition appears to be less associated with airway inflammation and may be related to autonomic dysfunction. en-copyright= kn-copyright= en-aut-name=TaharaDaisuke en-aut-sei=Tahara en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TaharaNao en-aut-sei=Tahara en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TamaiChisato en-aut-sei=Tamai en-aut-mei=Chisato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkagiAkio en-aut-sei=Akagi en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RikuYuichi en-aut-sei=Riku en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyaharaHiroaki en-aut-sei=Miyahara en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobayashiRei en-aut-sei=Kobayashi en-aut-mei=Rei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkadaHisashi en-aut-sei=Okada en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawamotoMichi en-aut-sei=Kawamoto en-aut-mei=Michi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiiJunko en-aut-sei=Ishii en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamazakiHiroki en-aut-sei=Yamazaki en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KurashigeTakashi en-aut-sei=Kurashige en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SugiyamaAtsuhiko en-aut-sei=Sugiyama en-aut-mei=Atsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NagaishiAkiko en-aut-sei=Nagaishi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NishidaKatsuya en-aut-sei=Nishida en-aut-mei=Katsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SugieKazuma en-aut-sei=Sugie en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FukudomeTakayasu en-aut-sei=Fukudome en-aut-mei=Takayasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HasegawaKazuko en-aut-sei=Hasegawa en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KoikeHaruki en-aut-sei=Koike en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KasaiTakashi en-aut-sei=Kasai en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MizunoToshiki en-aut-sei=Mizuno en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=AndoMasahiro en-aut-sei=Ando en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HiguchiYujiro en-aut-sei=Higuchi en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=TanakaFumiaki en-aut-sei=Tanaka en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IzumiYuishin en-aut-sei=Izumi en-aut-mei=Yuishin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=SobueGen en-aut-sei=Sobue en-aut-mei=Gen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=IwasakiYasushi en-aut-sei=Iwasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=ItoSatoru en-aut-sei=Ito en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SoneJun en-aut-sei=Sone en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=2 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=3 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=4 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=5 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=6 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=7 en-affil=Department of Neurology, NHO Nagoya Medical Center kn-affil= affil-num=8 en-affil=Department of Neurology, NHO Nagoya Medical Center kn-affil= affil-num=9 en-affil=Department of Neurology, Kobe City Medical Center General Hospital kn-affil= affil-num=10 en-affil=Department of Neurology, Kobe City Medical Center General Hospital kn-affil= affil-num=11 en-affil=Department of Neurology, Tokushima University Graduate School of Biomedical Science kn-affil= affil-num=12 en-affil=Department of Neurology, NHO Kure Medical Center and Chugoku Cancer Center kn-affil= affil-num=13 en-affil=Department of Neurology, Chiba University kn-affil= affil-num=14 en-affil=Department of Neurology, NHO Nagasaki Kawatana Medical Center kn-affil= affil-num=15 en-affil=Department of Neurology, NHO Hyogo Chuo National Hospital kn-affil= affil-num=16 en-affil=Department of Neurology, Nara Medical University Hospital kn-affil= affil-num=17 en-affil=Department of Neurology, NHO Nagasaki Kawatana Medical Center kn-affil= affil-num=18 en-affil=Department of Neurology, NHO Sagamihara National Hospital kn-affil= affil-num=19 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=20 en-affil=Department of Neurology, Saga University kn-affil= affil-num=21 en-affil=Department of Neurology, Kyoto Prefectural University of Medicine kn-affil= affil-num=22 en-affil=Department of Neurology, Kyoto Prefectural University of Medicine kn-affil= affil-num=23 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=24 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=25 en-affil=Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine kn-affil= affil-num=26 en-affil=Department of Neurology, Tokushima University Graduate School of Biomedical Science kn-affil= affil-num=27 en-affil=Aichi Medical University kn-affil= affil-num=28 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=29 en-affil=Division of Respiratory Medicine and Allergology, Department of Internal Medicine, School of Medicine, Aichi Medical University kn-affil= affil-num=30 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= en-keyword=Asthma kn-keyword=Asthma en-keyword=Autonomic dysfunction kn-keyword=Autonomic dysfunction en-keyword=Cough kn-keyword=Cough en-keyword=Neuronal intranuclear inclusion disease kn-keyword=Neuronal intranuclear inclusion disease en-keyword=NOTCH2NLC kn-keyword=NOTCH2NLC en-keyword=Pulmonary function kn-keyword=Pulmonary function END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=pcag056 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260428 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=NIMA-related kinases redundantly regulate vegetative and reproductive development in Arabidopsis thaliana en-subtitle= kn-subtitle= en-abstract= kn-abstract=Never-in-mitosis A-related kinases (NEKs) are conserved protein kinases in eukaryotes that regulate cell division and elongation. In Arabidopsis thaliana, NEK6 has been shown to control anisotropic growth through cortical microtubule depolymerization, but the functions of other NEK family members remain largely unknown. Here, we show that Arabidopsis NEKs redundantly regulate organ growth and flowering through phosphorylation-dependent mechanisms. Expression analyses revealed overlapping promoter activities of NEK genes in meristems, vascular tissues, and floral organs. While most single mutants showed no obvious phenotype, multiple mutants exhibited defects in root growth direction, leaf elongation, vascular formation, and floral transition. Biochemical analysis showed that NEK3 and NEK6 phosphorylate both β-tubulin and γ-tubulin, indicating a conserved role in microtubule regulation. In addition, several NEKs interacted with the florigen FLOWERING LOCUS T (FT), and NEK3 phosphorylated FT in vitro and inhibited the FT–FD interaction in transient assays, suggesting a role in flowering regulation. These findings show that Arabidopsis NEKs redundantly coordinate vegetative and reproductive development through phosphorylation-dependent regulation of microtubules and the flowering pathway. en-copyright= kn-copyright= en-aut-name=TakataniShogo en-aut-sei=Takatani en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanazawaMai en-aut-sei=Kanazawa en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakamotoKotaro en-aut-sei=Sakamoto en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomitaYuki en-aut-sei=Tomita en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawamotoNozomi en-aut-sei=Kawamoto en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakaiTatsuya en-aut-sei=Sakai en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ArakiTakashi en-aut-sei=Araki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MotoseHiroyasu en-aut-sei=Motose en-aut-mei=Hiroyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Biology, Faculty of Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Biology, Faculty of Science, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=5 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=6 en-affil=Graduate School of Science and Technology, Niigata University kn-affil= affil-num=7 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Arabidopsis thaliana kn-keyword=Arabidopsis thaliana en-keyword=flowering kn-keyword=flowering en-keyword=FLOWERING LOCUS T kn-keyword=FLOWERING LOCUS T en-keyword=NIMA-related kinase kn-keyword=NIMA-related kinase en-keyword=organ development kn-keyword=organ development en-keyword=tubulin kn-keyword=tubulin END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=11 article-no= start-page=1688 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260525 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=GLP-1 Receptor Agonists in the Rehabilitation of Patients with Heart Failure: Mechanisms, Clinical Evidence, and Future Perspectives en-subtitle= kn-subtitle= en-abstract= kn-abstract=Heart failure (HF) remains associated with high morbidity and mortality, with heart failure with preserved ejection fraction (HFpEF) becoming increasingly prevalent and therapeutically challenging despite advances in pharmacological and rehabilitative care. Beyond their glucose-lowering effects, glucagon-like peptide-1 receptor agonists (GLP-1RAs) confer cardiometabolic benefits and may serve as effective adjuncts to cardiac rehabilitation (CR), particularly in obese patients with HFpEF. Obesity plays a central role in the pathophysiology of HFpEF, and GLP-1RAs promote weight loss, reduce insulin resistance and leptin signaling, and improve hemodynamic and metabolic abnormalities associated with HFpEF. Accumulating evidence suggests that the benefits of GLP-1RAs are phenotype-specific and more pronounced in patients with HFpEF than in patients with HF with reduced ejection fraction. Current clinical guidelines recommend GLP-1RAs for patients who have type 2 diabetes mellitus and established cardiovascular (CV) disease or are at high CV risk, with recent updates recognizing their potential benefits in patients with HFpEF and obesity. Cardiac rehabilitation, delivered through multidisciplinary programs, remains a cornerstone of HF management. Although caloric restriction and aerobic exercise can be beneficial in patients with HFpEF and obesity, these interventions alone are often insufficient. Sarcopenia is common in older patients with HFpEF and contributes to adverse outcomes, underscoring the importance of incorporating resistance training into CR programs. The most frequent adverse effects of GLP-1RAs are gastrointestinal events, which are generally mild to moderate but may lead to treatment discontinuation in some patients. Future studies should investigate the potential synergistic effects of GLP-1RAs and CR, clarify their long-term safety and efficacy in HF populations, and define their role beyond obese HFpEF phenotypes. en-copyright= kn-copyright= en-aut-name=SuastikaLuh Oliva Saraswati en-aut-sei=Suastika en-aut-mei=Luh Oliva Saraswati kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BandoYasuko K. en-aut-sei=Bando en-aut-mei=Yasuko K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HoshinoKeiji en-aut-sei=Hoshino en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KoitabashiNorimichi en-aut-sei=Koitabashi en-aut-mei=Norimichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= 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 Molecular Physiology and Cardiovascular Biology, Mie University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Division of Cardiology, Gunma Prefectural Cardiovascular Center kn-affil= affil-num=4 en-affil=Division of Cardiology, Gunma Prefectural Cardiovascular Center 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= en-keyword=GLP-1 receptor agonists kn-keyword=GLP-1 receptor agonists en-keyword=heart failure kn-keyword=heart failure en-keyword=cardiac rehabilitation kn-keyword=cardiac rehabilitation en-keyword=obesity kn-keyword=obesity en-keyword=sarcopenia kn-keyword=sarcopenia END start-ver=1.4 cd-journal=joma no-vol=225 cd-vols= no-issue= article-no= start-page=111049 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Decline in rescue breathing and its impact on outcomes in pediatric out-of-hospital cardiac arrest due to drowning: a nationwide study, 2012–2023 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Rescue breathing is considered essential in pediatric out-of-hospital cardiac arrest (OHCA) due to drowning, a type of asphyxial arrest where hypoxia precedes circulatory collapse. However, the increasing promotion of compression-only CPR (CO-CPR) may have contributed to changes in bystander CPR practices, including a decline in rescue-breathing CPR (RB-CPR). Whether such temporal changes have influenced outcomes in pediatric drowning OHCA remains unclear.
Methods: We analyzed nationwide data from the All-Japan Utstein Registry (2012–2023), including pediatric OHCA patients (≤17 years old) whose arrests were caused by drowning and received bystander CPR from laypersons. Patients were categorized into RB-CPR and CO-CPR groups. The primary outcome was 30-day mortality; secondary outcomes included prehospital absence of return of spontaneous circulation (ROSC) and 30-day unfavorable neurological survival, defined as Cerebral Performance Category score 3–5. We used multivariable Poisson regression to estimate adjusted risk ratio (aRR) and conducted analyses by age and witnessed status.
Results: Among 740 eligible patients, 41.6% received RB-CPR and 58.4% received CO-CPR. The proportion of RB-CPR declined over the study period. CO-CPR was associated with higher 30-day mortality (aRR 1.38, 95% CI 1.14–1.67), higher prehospital absence of ROSC, and worse neurological outcomes compared with RB-CPR. The adverse association of CO-CPR was most pronounced in unwitnessed arrests, where ventilation may be particularly important.
Conclusions: In pediatric drowning OHCA, CO-CPR was associated with worse survival and neurological outcomes than RB-CPR. These findings underscore the necessity for rescue breathing and the importance of ventilation-focused bystander CPR training in pediatric and drowning-related scenarios. en-copyright= kn-copyright= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HongoTakashi en-aut-sei=Hongo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Drowning kn-keyword=Drowning en-keyword=Out-of-hospital cardiac arrest kn-keyword=Out-of-hospital cardiac arrest en-keyword=Cardiopulmo naryresuscitation kn-keyword=Cardiopulmo naryresuscitation en-keyword=Child kn-keyword=Child en-keyword=Asphyxia kn-keyword=Asphyxia END start-ver=1.4 cd-journal=joma no-vol= 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=10055 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nitric oxide induces p53-mediated cell death in human nasal epithelial cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nitric oxide (NO) is a key signaling molecule that plays a vital role in maintaining homeostasis of physiological processes such as immune responses and neurotransmission. However, excessive NO production during inflammatory responses to infection can lead to cytotoxicity and tissue damage. The nasal epithelial barrier is a crucial first line of immunological defense against viral infections, and it is likely exposed to excessive NO levels during chronic inflammation. Therefore, clarifying the effects of NO on this barrier is thus critical. In this study, we investigated the biological effects of sustained NO exposure on RPMI2650 human nasal epithelial cells. Post-NO exposure transcriptomic analyses revealed significant upregulation of genes involved in the p53 signaling pathway. RT-qPCR analyses confirmed the temporal upregulation of p53 target genes associated with apoptosis and cell cycle regulation. These gene expression changes downregulated cell proliferation and induced cell death. Our findings suggest that excessive NO exposure induces nasal epithelial cell death via the p53 pathway, which over the long term can result in tissue damage and dysfunction under inflammatory conditions. These results provide new insights into how prolonged NO exposure affects the nasal epithelial cells and may contribute to the progression of chronic infectious diseases. en-copyright= kn-copyright= en-aut-name=KamiuezonoShizuki en-aut-sei=Kamiuezono en-aut-mei=Shizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TsuchidaTomoki en-aut-sei=Tsuchida en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakasugiNobumasa en-aut-sei=Takasugi en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UeharaTakashi en-aut-sei=Uehara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Medicinal Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Nitric oxide kn-keyword=Nitric oxide en-keyword=p53 kn-keyword=p53 en-keyword=Apoptosis kn-keyword=Apoptosis en-keyword=Cell death kn-keyword=Cell death en-keyword=Human nasal epithelial cells kn-keyword=Human nasal epithelial cells 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=69 cd-vols= no-issue=1 article-no= start-page=e01108-24 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=Genomic epidemiology and genetic characteristics of clinical Campylobacter species cocirculating in West Bengal, India, 2019, using whole genome analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Campylobacter species are the most common pathogens responsible for foodborne gastroenteritis worldwide. India is a region with frequent diarrheal infections and a high level of Campylobacter infection incidence, but the detailed genomic information is limited. This study aimed to characterize 112 isolates of Campylobacter from diarrhea patients at two hospitals in Kolkata, West Bengal, by whole genome analysis. The Campylobacter isolates consisted of 90 C. jejuni, 20 C. coli, and 2 C. lari isolates. Multilocus sequence typing analysis revealed that the largest sequence type (ST) populations were ST-2131 in C. jejuni and ST-830 in C. coli and seven novel STs were found in C. jejuni and one in C. coli. Notably, ST-2131, which is rarely seen elsewhere, was positive for a sialylated LOS-related gene (wlaN +neuA + cstIII) associated with Guillain-Barré syndrome. Antibiotic resistance factors predicted from the genome sequence included blaOXA variants (58.9%), tet(O) (54.5%), tet(W) (0.9%), ant(6)-Ia (0.9%), mutation in GyrA (T86I, T86I+D90N, T86I+P104S, T86I+D90N+P104S) (79.5%), and mutation in 23S rRNA (A2075G) (12.5%). In addition to the high drug resistance of Campylobacter in Kolkata, Campylobacter pathogens were circulating that may be associated with Guillain-Barré syndrome. This study indicates the importance of genomic analysis in the surveillance of pathogens, which provides genomic information on genetic diversity, virulence mechanisms, and determinants of antimicrobial resistance. en-copyright= kn-copyright= en-aut-name=MoritaDaichi en-aut-sei=Morita en-aut-mei=Daichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MukhopadhyayAsish Kumar en-aut-sei=Mukhopadhyay en-aut-mei=Asish Kumar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChowdhuryGoutam en-aut-sei=Chowdhury en-aut-mei=Goutam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaruyamaFumito en-aut-sei=Maruyama en-aut-mei=Fumito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KandaMiyuki en-aut-sei=Kanda en-aut-mei=Miyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoYuki en-aut-sei=Yamamoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TaharaHidetoshi en-aut-sei=Tahara en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MukherjeePiyali en-aut-sei=Mukherjee en-aut-mei=Piyali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BardhanMainak en-aut-sei=Bardhan en-aut-mei=Mainak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KumagaiTakanori en-aut-sei=Kumagai en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KitaharaKei en-aut-sei=Kitahara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MiyoshiShin-Ichi en-aut-sei=Miyoshi en-aut-mei=Shin-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=DuttaShanta en-aut-sei=Dutta en-aut-mei=Shanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KurodaTeruo en-aut-sei=Kuroda en-aut-mei=Teruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Microbiology, Graduate School of Biomedical and Health Sciences, Hiroshima University 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=Section of Microbial Genomics and Ecology, The IDEC Institute, Hiroshima University kn-affil= affil-num=5 en-affil=Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=6 en-affil=Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=7 en-affil=Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=8 en-affil=Division of Bacteriology, ICMR - National Institute of Cholera and Enteric Diseases kn-affil= affil-num=9 en-affil=Division of Bacteriology, ICMR - National Institute of Cholera and Enteric Diseases kn-affil= affil-num=10 en-affil=Department of Microbiology, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=11 en-affil=Collaborative Research Centre of Okayama University for Infectious Diseases at ICMR-NICED kn-affil= affil-num=12 en-affil=Collaborative Research Centre of Okayama University for Infectious Diseases at ICMR-NICED kn-affil= affil-num=13 en-affil=Division of Bacteriology, ICMR - National Institute of Cholera and Enteric Diseases kn-affil= affil-num=14 en-affil=Department of Microbiology, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= en-keyword=Campylobacter jejuni/coli kn-keyword=Campylobacter jejuni/coli en-keyword=whole genome sequencing kn-keyword=whole genome sequencing en-keyword=phylogenetic analysis kn-keyword=phylogenetic analysis en-keyword=plasmid structure kn-keyword=plasmid structure END start-ver=1.4 cd-journal=joma no-vol=87 cd-vols= no-issue=6 article-no= start-page=680 end-page=684 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=Effects of heat stress on gene expression associated with antioxidant capacity of bovine early antral follicles en-subtitle= kn-subtitle= en-abstract= kn-abstract=Heat exposure at the physiological level of oocyte-cumulus-granulosa cell complexes (OCGCs) during in vitro growth (IVG) culture decreases the reduced glutathione (GSH) level of oocytes, an antioxidant, but its mechanism has been unclear. We subjected OCGCs to IVG for 4, 8, or 12 days and investigated the effects of heat exposure on the gene expression of cumulus-granulosa cells associated with antioxidant capacity. Heat exposure did not alter the expression of genes related to GSH synthesis or reuse. Conversely, heat exposure increased mRNA expression of superoxide dismutase 2 and decreased that of glutathione peroxidase 1, which are antioxidant enzymes. Ultimately, heat exposure alters the gene expression of antioxidant enzymes in growing follicles, which may indirectly decrease the GSH level of oocytes. en-copyright= kn-copyright= en-aut-name=KAWANOKohei en-aut-sei=KAWANO en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SAKAGUCHIKenichiro en-aut-sei=SAKAGUCHI en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FURUKAWAEri en-aut-sei=FURUKAWA en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NINPETCHNattapong en-aut-sei=NINPETCH en-aut-mei=Nattapong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YANAGAWAYojiro en-aut-sei=YANAGAWA en-aut-mei=Yojiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KATAGIRISeiji en-aut-sei=KATAGIRI en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Laboratory of Reproductive Physiology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Laboratory of Veterinary Theriogenology, Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University kn-affil= affil-num=3 en-affil=National Institute of Animal Health, National Agriculture and Food Research Organization kn-affil= affil-num=4 en-affil=Department of Animal Science, Faculty of Agriculture at Kamphaeng Saen, Kasetsart University kn-affil= affil-num=5 en-affil=Laboratory of Theriogenology, Department of Clinical Sciences, Division of Veterinary Medicine, Faculty of Veterinary Medicine, Hokkaido University kn-affil= affil-num=6 en-affil=Laboratory of Theriogenology, Department of Clinical Sciences, Division of Veterinary Medicine, Faculty of Veterinary Medicine, Hokkaido University kn-affil= en-keyword=antioxidant capacity kn-keyword=antioxidant capacity en-keyword=bovine kn-keyword=bovine en-keyword=early antral follicle kn-keyword=early antral follicle en-keyword=in vitro growth kn-keyword=in vitro growth en-keyword=oxidative stress kn-keyword=oxidative stress END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=12 article-no= start-page=2058 end-page=2064 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241213 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Staphylococcus aureus δ-Toxin Induces Ca2+ Influx-Independent Degranulation of Murine Cultured Mast Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cutaneous colonization with Staphylococcus aureus (SA) is frequently observed in patients with atopic dermatitis. SA produces a wide variety of bacterial toxins, among which δ-toxin was found to induce degranulation of mast cells. Degranulation of mast cells could enhance bacterial clearance and protection from future SA infection but lead to exacerbation of atopic dermatitis. Because it remains to be determined how δ-toxin triggers degranulation, we investigated δ-toxin-induced changes in murine bone marrow-derived cultured mast cells in this study. We found that δ-toxin-induced degranulation could be classified into two phases, an early Ca2+-independent and a late Ca2+-dependent phase. Recent studies suggest that NOD-like receptor family, pyrin domain containing 3 is involved in the degranulation of mast cells, raising a possibility that leakage of K+ induced by δ-toxin is involved in the Ca2+-independent phase. However, Ca2+-independent degranulation remains unchanged although Ca2+-influx and degranulation induced by δ-toxin were significantly suppressed in the presence of high concentrations of K+. Because actin depolymerization was reported to induce degranulation in the absence of Ca2+ in the permeabilized rat peritoneal mast cells, a slow but steady decrease in the amount of filamentous actin observed here may be involved in Ca2+-independent degranulation induced by δ-toxin. Although Mas-related G protein-coupled receptor (MRGPR) X2 in humans and Mrgprb2 in mice are regarded as the receptors responsible for immunoglobulin E-independent degranulation, δ-toxin-induced degranulation remained unchanged in Mrgprb2−/− mast cells. Our findings pave the way for identification of the target receptors of δ-toxin. en-copyright= kn-copyright= en-aut-name=LiuKang en-aut-sei=Liu en-aut-mei=Kang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatayamaTomoaki en-aut-sei=Katayama en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoHitomi en-aut-sei=Sato en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Hamaoka-TamuraYuho en-aut-sei=Hamaoka-Tamura en-aut-mei=Yuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoMichiko en-aut-sei=Saito en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FurutaKazuyuki en-aut-sei=Furuta en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaSatoshi en-aut-sei=Tanaka en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Laboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University kn-affil= affil-num=2 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Laboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University kn-affil= affil-num=5 en-affil=Bioscience Research Center, Kyoto Pharmaceutical University kn-affil= affil-num=6 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Laboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University kn-affil= en-keyword=mast cell kn-keyword=mast cell en-keyword=δ-toxin kn-keyword=δ-toxin en-keyword=degranulation kn-keyword=degranulation en-keyword=inflammation kn-keyword=inflammation en-keyword=Mas-related G protein-coupled receptor kn-keyword=Mas-related G protein-coupled receptor END start-ver=1.4 cd-journal=joma no-vol=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=18 cd-vols= no-issue=7 article-no= start-page=e112232 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260707 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Reappraisal of the Entity of Pediatric Uveitis: Bilateral Iridocyclitis With Retinal Capillaritis (BIRC) in Juveniles in 18 Additional Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Bilateral iridocyclitis with retinal capillaritis (BIRC) in juveniles is a newly recognized ​​​​​entity of juvenile chronic uveitis with no systemic involvement. In this study, 18 additional consecutive patients with BIRC were reported to show that the entity would be useful in the differential diagnosis.
Methods: Clinical features were retrospectively reviewed in 18 consecutive patients diagnosed with BIRC in juveniles at Okayama University Hospital, Okayama, Japan, between 1996 and 2025.
Results: The 18 patients comprised 6 males and 12 females, with an age at onset ranging from 9 to 16 years (median, 13 years). All patients presented with aqueous cells and mutton-fat keratic precipitates in both eyes, and fluorescein angiography revealed varying degrees of optic disc leakage and retinal capillary leakage in the midperipheral to peripheral fundus of both eyes. None had systemic symptoms, including skin rashes, joint pain, or fever, and no abnormalities were detected on blood examinations, urinalysis, or plain chest x-rays. Oral prednisolone, tapered from 30 mg daily, together with topical 0.1% betamethasone four times daily, was administered to five patients: two with optic disc edema and three with macular edema in both eyes or the unilateral eye. The remaining 13 patients were treated with topical 0.1% betamethasone eye drops alone. In patients who developed elevated intraocular pressure, often due to a steroid response, the instillation of topical 0.1% betamethasone was reduced to twice daily, or intraocular pressure-lowering eye drops were used in combination. In two patients who showed relapse of unilateral macular edema after oral prednisolone was tapered or discontinued, oral colchicine (1 mg daily) was introduced, resulting in the subsidence of macular edema. Bilateral uveitis in all 18 patients subsided within 6 months to a few years until 19 years of age, and all topical medications were discontinued, with relapse occurring in only one patient.
Conclusions: BIRC in juveniles should be included in the differential diagnosis for school-age children and young adolescents. BIRC follows a chronic course of a few years and subsides completely with a good prognosis. In cases of macular edema or optic disc edema that affects vision, oral corticosteroid treatment is recommended, whereas patients with no sight-threatening signs can be treated with topical corticosteroid eye drops alone. The entity of BIRC may be distinct from juvenile chronic iridocyclitis in young girls with onset at preschool age, which shares common features with juvenile idiopathic arthritis-associated uveitis. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=bilateral iridocyclitis with retinal capillaritis (birc) kn-keyword=bilateral iridocyclitis with retinal capillaritis (birc) en-keyword=colchicine kn-keyword=colchicine en-keyword=corticosteroid kn-keyword=corticosteroid en-keyword=fluorescein angiography kn-keyword=fluorescein angiography en-keyword=juvenile kn-keyword=juvenile en-keyword=juvenile chronic iridocyclitis (jci) kn-keyword=juvenile chronic iridocyclitis (jci) en-keyword=juvenile idiopathic arthritis (jia) kn-keyword=juvenile idiopathic arthritis (jia) en-keyword=macular edema kn-keyword=macular edema en-keyword=optical coherence tomography kn-keyword=optical coherence tomography en-keyword=optic disc edema kn-keyword=optic disc edema 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=392 cd-vols= no-issue=1 article-no= start-page=1051 end-page=1097 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Global well-posedness and scattering in weighted space for nonlinear Schrödinger equations below the Strauss exponent without gauge-invariance en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this paper, we consider the nonlinear Schrödinger equation (NLS) with a general homogeneous nonlinearity in dimensions up to three. We assume that the degree (i.e., power) of the nonlinearity is such that the equation is mass-subcritical and short-range. We establish global well-posedness (GWP) and scattering for small data in the standard weighted space for a class of homogeneous nonlinearities, including non-gauge-invariant ones. Additionally, we include the case where the degree is less than or equal to the Strauss exponent. When the nonlinearity is not gauge-invariant, the standard Duhamel formulation fails to work effectively in the weighted Sobolev space; for instance, the Duhamel term may not be well-defined as a Bochner integral. To address this issue, we introduce an alternative formulation that allows us to establish GWP and scattering, even in the presence of poor time continuity of the Duhamel term. en-copyright= kn-copyright= en-aut-name=KawamotoMasaki en-aut-sei=Kawamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MasakiSatoshi en-aut-sei=Masaki en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyazakiHayato en-aut-sei=Miyazaki en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Mathematics, Hokkaido University kn-affil= affil-num=3 en-affil=Teacher Training Courses, Faculty of Education, Kagawa University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=40 cd-vols= no-issue=4 article-no= start-page=561 end-page=568 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240705 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Central dentinogenic ghost cell tumor of the maxilla: a case report with new imaging findings and review of the literature en-subtitle= kn-subtitle= en-abstract= kn-abstract=A dentinogenic ghost cell tumor (DGCT) is a rare benign odontogenic tumor that commonly shows characteristics of solid proliferation and has a relatively high risk of recurrence after surgical treatment. We herein report a case of a central DGCT that occurred in the maxilla and resulted in bone expansion. This study highlights new imaging findings (particularly magnetic resonance imaging) along with histopathological observations. In addition, we conducted a review of the existing literature on this rare tumor. A 37-year-old man developed swelling around the right cheek. A benign odontogenic tumor such as ameloblastoma was suspected based on the imaging examination findings (including bone expansion and the internal characteristics of the tumor) on panoramic imaging, computed tomography, and magnetic resonance imaging. The lesion was surgically excised from the right maxilla. Postoperative histopathological examination led to a definitive diagnosis of central DGCT. The tumor comprised epithelial neoplastic islands, resembling ameloblastoma, inside tight fibroconnective tissue; masses of ghost cells and formation of dentin were also observed. We had suspected that the minute high-density region around the molars on the imaging examinations represented alveolar bone change; however, it represented dentin formation. This led to difficulty diagnosing the lesion. Although DGCT may present characteristic findings on imaging examinations, its occurrence is infrequent, and in some cases, the findings may include the presence or absence of an impacted tooth without obvious calcification. The present case suggests that we should consider the possibility of an odontogenic tumor with calcification when high-density structures are observed inside the lesion. en-copyright= kn-copyright= en-aut-name=YoshidaSuzuka en-aut-sei=Yoshida en-aut-mei=Suzuka 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=KawazuToshiyuki en-aut-sei=Kawazu en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=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=FujikuraMamiko en-aut-sei=Fujikura en-aut-mei=Mamiko 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=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=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=AsaumiJunichi en-aut-sei=Asaumi en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Preliminary Examination Room, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Dentinogenic ghost cell tumor kn-keyword=Dentinogenic ghost cell tumor en-keyword=Benign odontogenic tumor kn-keyword=Benign odontogenic tumor en-keyword=Maxilla kn-keyword=Maxilla en-keyword=Calcification kn-keyword=Calcification en-keyword=Computed tomography kn-keyword=Computed tomography en-keyword=Magnetic resonance imaging kn-keyword=Magnetic resonance imaging END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue=5 article-no= start-page=upaf091 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Highly emissive and robust diarylethene fluorophore incorporating imide-fused phenanthryl moieties en-subtitle= kn-subtitle= en-abstract= kn-abstract=The fluorescence properties and photostabilities of (E)-diarylethenes (DPEs), featuring two 3-phenanthryl moieties, were investigated. Pristine (E)-di-1,2-(3-phenanthryl)ethene and its ester derivative, respectively referred to as DPE-H and DPE-E, exhibited blue fluorescence. However, they underwent a two-step photoreaction sequence that yielded [7]helicenes, resulting in a gradual reduction of the fluorescence intensity. In contrast, the imide-fused derivative DPE-I displayed intense green fluorescence and it was unexpectedly photostable in solution, maintaining its highly efficient fluorescent nature even after prolonged light exposure. DPE-I, thus, provides a new type of highly efficient and robust diarylethene fluorophore. en-copyright= kn-copyright= en-aut-name=NoseKeito en-aut-sei=Nose en-aut-mei=Keito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamajiMinoru en-aut-sei=Yamaji en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriTadashi en-aut-sei=Mori en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniFumito en-aut-sei=Tani en-aut-mei=Fumito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotoKenta en-aut-sei=Goto en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkamotoHideki en-aut-sei=Okamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Program of Applied Chemistry, Cluster of Materials and Environment, Gunma University kn-affil= affil-num=3 en-affil=Research Center for Environmental Preservation and Graduate School of Engineering, The University of Osaka kn-affil= affil-num=4 en-affil=Institute for Materials Chemistry and Engineering, Kyushu University kn-affil= affil-num=5 en-affil=Institute for Materials Chemistry and Engineering, Kyushu University kn-affil= affil-num=6 en-affil=Department of Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=diarylethene kn-keyword=diarylethene en-keyword=fluorescence kn-keyword=fluorescence en-keyword=phenanthreneimide kn-keyword=phenanthreneimide END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=1 end-page=4 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=Indicators for Monitoring Recovery From Surgery to Discharge Using Accelerometer in Patients With Esophageal Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Esophageal cancer is a highly invasive malignancy necessitating esophagectomy, which is associated with considerable postoperative morbidity and prolonged hospitalization. Enhanced Recovery After Surgery (ERAS) protocols recommend early mobilization to facilitate recovery; however, objectively assessing physical activity during hospitalization remains challenging. Traditional methods, such as the 6-min walk test or patient-reported questionnaires can be burdensome, or may not accurately reflect recovery. Accelerometer-based measurement provides a low-burden, objective approach, but previous studies focused on the immediate postoperative period or long after discharge, leaving the recovery trajectory from surgery to discharge underexplored. en-copyright= kn-copyright= en-aut-name=YamaneTakahiro en-aut-sei=Yamane en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraYoshikazu en-aut-sei=Kimura en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TetsutaniManami en-aut-sei=Tetsutani en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamuraShota en-aut-sei=Yamamura en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItoAiru en-aut-sei=Ito en-aut-mei=Airu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanumaMoe en-aut-sei=Tanuma en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HonjohMina en-aut-sei=Honjoh en-aut-mei=Mina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MoriwakiYoshiko en-aut-sei=Moriwaki en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaedaNaoaki en-aut-sei=Maeda en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsuokaYoshikazu en-aut-sei=Matsuoka en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MoritaMizuki en-aut-sei=Morita en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Biomedical Informatics, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Faculty of Health Sciences, Okayama University Medical School kn-affil= affil-num=4 en-affil=Faculty of Health Sciences, Okayama University Medical School kn-affil= affil-num=5 en-affil=Faculty of Health Sciences, Okayama University Medical School kn-affil= affil-num=6 en-affil=Faculty of Health Sciences, Okayama University Medical School kn-affil= affil-num=7 en-affil=Faculty of Health Sciences, Okayama University Medical School kn-affil= affil-num=8 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Biomedical Informatics, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=14 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=actigraphy kn-keyword=actigraphy en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=monitoring indicator kn-keyword=monitoring indicator en-keyword=physical activity kn-keyword=physical activity en-keyword=postoperative recovery kn-keyword=postoperative recovery en-keyword=surgery‐to‐discharge kn-keyword=surgery‐to‐discharge END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=1866 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250221 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Grain boundary diffusion cannot explain the W isotope heterogeneities of the deep mantle en-subtitle= kn-subtitle= en-abstract= kn-abstract=The low 182W/184W and high 3He/4He in some ocean island basalts compared to the bulk mantle values may derive from the Earth’s core through long-term core-mantle interactions. It has been proposed that the grain boundary diffusion of siderophile elements is an efficient mechanism for core-mantle interaction and may effectively modify the W isotopic compositions of the plume-source mantle. In this study, we perform large-scale molecular dynamics simulations driven by machine learning potentials of ab initio quality to investigate the diffusion of W along ferropericlase grain boundaries and in (Mg,Fe)O liquid. Here we show that the diffusion of W is sluggish under core-mantle boundary conditions, and thus is unlikely to have observable impacts on the W isotopic compositions of terrestrial igneous rocks. en-copyright= kn-copyright= en-aut-name=PengYihang en-aut-sei=Peng en-aut-mei=Yihang 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=DengJie en-aut-sei=Deng en-aut-mei=Jie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Geosciences, Princeton University kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=Department of Geosciences, Princeton University kn-affil= 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=111 cd-vols= no-issue=5 article-no= start-page=1705 end-page=1715 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250911 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Distinct interleukin-6 production in IPL and TAFRO subtypes of idiopathic multicentric Castleman disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder characterized by systemic inflammation and lymphadenopathy. Two major clinical subtypes, idiopathic plasmacytic lymphadenopathy (iMCD-IPL) and iMCD with thrombocytopenia, anasarca, fever, renal dysfunction/reticulin fibrosis, and organomegaly (iMCD-TAFRO), have distinct pathophysiological mechanisms. While interleukin-6 (IL-6) is known to be elevated in iMCD, differences in the sources of IL-6 production between subtypes remain unclear. We examined the source of IL-6 production and its transcriptional regulation across iMCD subtypes using immunohistochemistry, in situ hybridization, and gene expression profiling. Immunohistochemistry and in situ hybridization revealed that plasma cells were the predominant IL-6-expressing cells in iMCD-IPL, whereas vascular endothelial cells expressed IL-6 in iMCD-TAFRO. Plasma cells exhibited stronger IL-6 protein expression in iMCD-IPL than in iMCD-TAFRO. Gene expression analysis revealed upregulation of XBP1, MZB1, DERL3, SSR4, FKBP11, FKBP2, PIM2, RABAC1, and SDF2L1 in iMCD-IPL, implicating endoplasmic reticulum stress and plasma cell differentiation in IL-6 dysregulation. Our findings suggest that XBP1-mediated IL-6 production may contribute to the pathogenesis of iMCD-IPL, potentially explaining its favorable responses to IL-6 blockade therapy. In contrast, IL-6 production in iMCD-TAFRO may be predominantly from vascular endothelial cells, suggesting that elevated serum IL-6 is a secondary phenomenon of the cytokine storm in this subtype. Future studies should clarify how proteomics and gene expression profiling could inform subtype-specific therapeutic strategies in iMCD. en-copyright= kn-copyright= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamadaRio en-aut-sei=Yamada en-aut-mei=Rio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaratakeTomoka en-aut-sei=Haratake en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=ChijimatsuRyota en-aut-sei=Chijimatsu en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ItoToshihiro en-aut-sei=Ito en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KogaTomohiro en-aut-sei=Koga en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OchiSayaka en-aut-sei=Ochi en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawaharaYuri en-aut-sei=Kawahara en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UetaHimawari en-aut-sei=Ueta en-aut-mei=Himawari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakedaYudai en-aut-sei=Takeda en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=GonzalezMichael V. en-aut-sei=Gonzalez en-aut-mei=Michael V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FajgenbaumDavid C. en-aut-sei=Fajgenbaum en-aut-mei=David C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Van RheeFrits en-aut-sei=Van Rhee en-aut-mei=Frits kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MomoseShuji en-aut-sei=Momose en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Division of Hematology/Oncology, Mayo Clinic kn-affil= affil-num=4 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, Japan; Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, Japan; Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Immunology, Nara Medical University kn-affil= affil-num=9 en-affil=Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=10 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=11 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=12 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=13 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=14 en-affil=Center for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=15 en-affil=Center for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=16 en-affil=University of Arkansas for Medical Sciences kn-affil= affil-num=17 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=18 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=207 cd-vols= no-issue= article-no= start-page=106961 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of secondary hydrothermal fluids on gallium distribution and coordination in hot springs silica using Ga K-edge XANES en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gallium (Ga), a critical element in the electronics industry, is enriched in hot spring silica deposits (sinter) at concentrations comparable to, and in some cases greater than, bauxite, coal, and sphalerite deposits from which it is currently extracted. Focusing on well characterized Holocene and Pleistocene New Zealand sinters, we utilize synchrotron-X-ray fluorescence (sXRF) and Ga K-edge X-ray absorption near edge structure (XANES) spectroscopy to examine the spatial distribution of Ga as well as its changing coordination number. Ga+3 is the only observed oxidation state in the analyzed sinters. Gallium is predominantly found in tetrahedral coordination in sinter deposited from alkali chloride fluids, with analyses best matching Ga-aluminosilicate standards. However, Ga coordination is octahedral in sinter samples that have undergone alteration by acidic fluids/gases, associated with a change in hydrology from alkali-chloride to acid-sulfate fluid conditions. High Ga concentrations are found associated with both these coordination environments, with a heterogeneous distribution. Octahedral Ga is observed both as particles and in larger regions affected by Fe-rich fluid overprinting. The combined use of sXRF and XANES demonstrates an ability to fingerprint diagenesis and alteration in these complex geothermal settings where tetrahedral and octahedral Ga co-exist. The transition from tetrahedral to octahedral Ga also appears to mimic the inferred natural process forming lateritic bauxite deposits, where remobilized tetrahedral Ga is reconcentrated and adsorbed to oxides. A similar process may occur for sinter Ga enrichment, whereby introduced Ga in acidic conditions is adsorbed to oxide phases as the Fe-rich secondary fluids infiltrate porous sinter material. en-copyright= kn-copyright= en-aut-name=RoweM.C. en-aut-sei=Rowe en-aut-mei=M.C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=CampbellK.A. en-aut-sei=Campbell en-aut-mei=K.A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=StallardD.A. en-aut-sei=Stallard en-aut-mei=D.A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LyonB. en-aut-sei=Lyon en-aut-mei=B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LangendamA. en-aut-sei=Langendam en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KalininaE. en-aut-sei=Kalinina en-aut-mei=E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamanakaM. en-aut-sei=Yamanaka en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaR. en-aut-sei=Tanaka en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ChristopherT. en-aut-sei=Christopher en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=RuffS.W. en-aut-sei=Ruff en-aut-mei=S.W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NersezovaE. en-aut-sei=Nersezova en-aut-mei=E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OtaT. en-aut-sei=Ota en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HamiltonA. en-aut-sei=Hamilton en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=School of Environment, University of Auckland kn-affil= affil-num=2 en-affil=School of Environment, University of Auckland kn-affil= affil-num=3 en-affil=School of Environment, University of Auckland kn-affil= affil-num=4 en-affil=School of Environment, University of Auckland kn-affil= affil-num=5 en-affil=Australian Synchrotron Facility (Ansto) kn-affil= affil-num=6 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=7 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=8 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=9 en-affil=School of Chemical Sciences, University of Auckland kn-affil= affil-num=10 en-affil=Arizona State University, School of Earth And Space Exploration kn-affil= affil-num=11 en-affil=School of Environment, University of Auckland kn-affil= affil-num=12 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=13 en-affil=School of Environment, University of Auckland kn-affil= en-keyword=Hot springs kn-keyword=Hot springs en-keyword=New Zealand kn-keyword=New Zealand en-keyword=Gallium kn-keyword=Gallium en-keyword=Sinter kn-keyword=Sinter en-keyword=Synchrotron radiation kn-keyword=Synchrotron radiation en-keyword=Coordination number kn-keyword=Coordination number END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=6 article-no= start-page=998 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260613 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Disease-Suppressive Activity of Lecithin Against Foliar Infection by Rhizoctonia solani Isolates in Cabbage, Rice, and Brachypodium distachyon en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rhizoctonia solani is a necrotrophic phytopathogenic fungus that causes disease in various crops. In agriculture, many crops suffer from root or seedling rot caused by this soil-borne pathogen, whereas cabbage and rice develop lesion-like symptoms on aboveground tissues. Diseases caused by R. solani are generally controlled using chemical fungicides; however, environmentally friendly alternatives are needed for sustainable agriculture. In this study, we evaluated the efficacy of lecithin, a mixture of phospholipids previously registered in Japan as an agrochemical for controlling cucumber powdery mildew, against Rhizoctonia diseases. In cabbage, foliar spraying of 0.2–1.0% soybean lecithin effectively suppressed leaf symptoms caused by R. solani isolate RhiCa-2, which was identified as AG-1 IB. In rice and Brachypodium distachyon, 0.2–1.0% lecithin significantly suppressed leaf symptoms induced by R. solani AG-1 IA. Hyphal staining of inoculated leaves revealed reduced hyphal density on lecithin-treated leaves. Consistently, hyphal growth of R. solani on cellophane placed on water agar was retarded by lecithin treatment. However, 5.0% lecithin induced phytotoxicity in B. distachyon. Egg yolk-derived lecithin also exhibited disease-suppressive activity in cabbage and B. distachyon, with efficacy comparable to that of soybean lecithin under the conditions tested. These results suggest that lecithin suppresses foliar infection by R. solani, at least in part, through direct inhibitory effects on fungal hyphae, and may serve as a potential alternative material for disease control in sustainable crop production. en-copyright= kn-copyright= en-aut-name=CuongTran Xuan en-aut-sei=Cuong en-aut-mei=Tran Xuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsanoMisaki en-aut-sei=Asano en-aut-mei=Misaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HonmaDaiki en-aut-sei=Honma en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SoedaMoeko en-aut-sei=Soeda en-aut-mei=Moeko 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=IkedaKentaro en-aut-sei=Ikeda en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=School of Agriculture, Okayama University kn-affil= affil-num=3 en-affil=School of Agriculture, 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= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University, Okayama 700-8530, Japan 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=Faculty of Bioscience and Applied Chemistry, Hosei University kn-affil= affil-num=11 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Rhizoctonia solani kn-keyword=Rhizoctonia solani en-keyword=foliar symptoms kn-keyword=foliar symptoms en-keyword=leaf infection kn-keyword=leaf infection en-keyword=cabbage kn-keyword=cabbage en-keyword=rice kn-keyword=rice en-keyword=Brachypodium distachyon kn-keyword=Brachypodium distachyon END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=6 article-no= start-page=992 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=UGT76B1 and 41 Additional Arabidopsis UDP-Glycosyltransferases Show No Detectable In Vitro Glycosylation Activity Toward N-Hydroxypipecolic Acid en-subtitle= kn-subtitle= en-abstract= kn-abstract=N-hydroxypipecolic acid (NHP) is a key mobile signal in systemic acquired resistance in plants, and its glycosylation has been proposed to regulate immune signaling. Previous studies have demonstrated that the UDP-glycosyltransferase UGT76B1, known as an SA glycosyltransferase in Arabidopsis thaliana, also catalyzes NHP glycosylation. In this study, we re-evaluated NHP glycosylation activity of UGT76B1 using an in vitro enzyme-coupled fluorescence assay that quantitatively detects UDP released during UDP-sugar-dependent glycosylation. Unexpectedly, our biochemical analyses demonstrated that UGT76B1 lacks genuine glycosylation activity toward NHP under the in vitro assay conditions tested, although this system clearly detected UGT76B1 activity toward salicylic acid (SA), as well as the activities of UGT74F1 and UGT72B1 toward SA and hydroquinone, respectively. To explore potential UGTs responsible for NHP glycosylation, we evaluated the enzymatic activities of 41 UGT candidates successfully expressed in Escherichia coli, which are selected based on transcriptomic responses to tenoxicam treatment, molecular docking simulations using AlphaFold3/AutoDock Vina, phylogenetic criteria, and previous reports. Within this selected and successfully expressed UGT panel, none exhibited authentic NHP glycosylation activity, although this does not preclude the possibility that other members of the Arabidopsis UGT family possess NHP glycosyltransferase activity. Our findings challenge the prevailing view that UGT76B1 is the primary glycosyltransferase for NHP in A. thaliana and indicate that NHP metabolism may rely on undiscovered non-canonical enzymes or distinct metabolic pathways that warrant further investigation. en-copyright= kn-copyright= en-aut-name=BaoJiyuan en-aut-sei=Bao en-aut-mei=Jiyuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchiyamaTaiga en-aut-sei=Uchiyama en-aut-mei=Taiga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KusunokiKazuki en-aut-sei=Kusunoki en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShinoharaYuka en-aut-sei=Shinohara en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanigawaYurika en-aut-sei=Tanigawa en-aut-mei=Yurika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 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=10 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=11 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=School of Agriculture, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=UGT76B1 kn-keyword=UGT76B1 en-keyword=N-hydroxypipecolic acid (NHP) kn-keyword=N-hydroxypipecolic acid (NHP) en-keyword=salicylic acid (SA) kn-keyword=salicylic acid (SA) en-keyword=glycosyltransferase kn-keyword=glycosyltransferase en-keyword=plant immunity kn-keyword=plant immunity END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=5705 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260119 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Variations in the perceived value of anti-SARS-CoV-2 therapeutics based on physicians’ clinical backgrounds en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although the global emergency phase of the coronavirus disease 2019 (COVID-19) pandemic has ended, antiviral therapy remains crucial for patients at high risk of severe illness. In Japan, the out-of-pocket costs for antiviral drugs shifted from full public coverage to partial patient payment in April 2024. However, the impact of physicians’ background characteristics on antiviral cost perceptions and prescribing behavior remains underexplored. This study involved a secondary analysis of a nationwide, web-based interventional survey of 1,500 physicians treating COVID-19. Participants reported whether they avoided prescribing antivirals owing to drug costs and identified what they considered an appropriate cost per treatment course. Associations between physicians’ characteristics and their cost perceptions were analyzed. Among 1,500 physicians surveyed, 1,193 (79.5%) reported avoiding antiviral prescriptions owing to drug costs. The most commonly selected appropriate cost was ≤ 33 USD (65.0%). Generalists, pulmonologists, ear, nose, and throat specialists, and clinic-based physicians were more likely to refrain from prescribing antivirals and favor lower treatment costs compared with physicians in other specialties or hospital settings. A multivariate analysis revealed workplace setting as the only factor independently associated with cost-related prescribing behavior. High antiviral drug costs in Japan may contribute to underprescription, particularly among clinic-based physicians, and this underprescription could hypothetically lead to delays in treatment, which might increase the risk of severe outcomes in high-risk patients. As high-risk patients with mild COVID-19 often first seek care in clinics, promoting appropriate antiviral use in these settings is essential. Strengthening communication and sharing clinical experiences between hospitals and clinics may help reduce prescribing disparities driven by drug costs. en-copyright= kn-copyright= en-aut-name=HagiwaraAkihiko en-aut-sei=Hagiwara en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KomiyaKosaku en-aut-sei=Komiya en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShindoYuichiro en-aut-sei=Shindo en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakamatsuKazufumi en-aut-sei=Takamatsu en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimuraNaoki en-aut-sei=Nishimura en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakechiYukako en-aut-sei=Takechi en-aut-mei=Yukako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakazonoTakahiro en-aut-sei=Takazono en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IzumiShinyu en-aut-sei=Izumi en-aut-mei=Shinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GotohShimpei en-aut-sei=Gotoh en-aut-mei=Shimpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakaoSeiichiro en-aut-sei=Sakao en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IzumoTakehiro en-aut-sei=Izumo en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoKazuko en-aut-sei=Yamamoto en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YateraKazuhiro en-aut-sei=Yatera en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KakeyaHiroshi en-aut-sei=Kakeya en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShibataYoko en-aut-sei=Shibata en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TomiiKeisuke en-aut-sei=Tomii en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SagaraHironori en-aut-sei=Sagara en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SasakiYuka en-aut-sei=Sasaki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HiraiToyohiro en-aut-sei=Hirai en-aut-mei=Toyohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YokoyamaAkihito en-aut-sei=Yokoyama en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MukaeHiroshi en-aut-sei=Mukae en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=OguraTakashi en-aut-sei=Ogura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine kn-affil= affil-num=2 en-affil=Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Nagoya University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, National Center for Global Health and Medicine kn-affil= affil-num=6 en-affil=Iki-iki Clinic kn-affil= affil-num=7 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, National Center for Global Health and Medicine kn-affil= affil-num=10 en-affil=Department of Clinical Application, Center for iPS Cell, Research and Application, Kyoto University kn-affil= affil-num=11 en-affil=Department of Pulmonary Medicine, School of Medicine, International University of Health and Welfare kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Japanese Red Cross Medical Center kn-affil= affil-num=13 en-affil=Division of Infectious, Respiratory, and Digestive Medicine, First Department of Internal Medicine, University of the Ryukyus Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health kn-affil= affil-num=15 en-affil=Department of Infection Control Science, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Pulmonary Medicine, Fukushima Medical University School of Medicine kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Kobe City Medical Center General Hospital kn-affil= affil-num=18 en-affil=Department of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University School of Medicine kn-affil= affil-num=19 en-affil=Center for Pulmonary Disease, National Hospital Organization Tokyo National Hospital kn-affil= affil-num=20 en-affil=Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University kn-affil= affil-num=21 en-affil=Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University kn-affil= affil-num=22 en-affil=Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=23 en-affil=Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center kn-affil= en-keyword=Antiviral kn-keyword=Antiviral en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=Prescription kn-keyword=Prescription en-keyword=Workplace kn-keyword=Workplace END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=3 article-no= start-page=213 end-page=217 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Novel Flap Design to Reduce Urethral Complications in Anterolateral Thigh Phalloplasty: The Pipe Flap Technique en-subtitle= kn-subtitle= en-abstract= kn-abstract=Phalloplasty is one of the most challenging procedures in gender-affirming surgery, and urethral complications remain common despite numerous preventive efforts. No definitive solution has been established, and many patients still require subsequent corrective procedures. We designed a novel anterolateral thigh flap that creates a planned external fistula at the penile base to mitigate urethral complications. The fistula was closed in a second-stage procedure one year later, and the postoperative course was uneventful. We report a case of a transgender man treated with this two-stage “pipe flap” technique, resulting in satisfactory urinary function. This approach may offer a safe and less invasive option for mitigating urethral complications in phalloplasty. en-copyright= kn-copyright= en-aut-name=ImaiToshiro en-aut-sei=Imai en-aut-mei=Toshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeToshiyuki en-aut-sei=Watanabe en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeShiho en-aut-sei=Watanabe en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HayashiMasanobu en-aut-sei=Hayashi en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NambaYuzaburo en-aut-sei=Namba en-aut-mei=Yuzaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Plastic and Reconstructive Surgery, National Hospital Organization Tokyo Medical Center kn-affil= affil-num=4 en-affil=Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Gender Center, Okayama University Hospital kn-affil= en-keyword=phalloplasty kn-keyword=phalloplasty en-keyword=surgical flaps kn-keyword=surgical flaps en-keyword=transgender persons kn-keyword=transgender persons END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=3 article-no= start-page=203 end-page=212 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of Bone Mineral Density and Bone Structure in the Cervical and Thoracic Spine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dropped head syndrome, which has been increasingly reported in recent years, requires correction of cervical kyphosis and may require long-range fixation extending from the cervical to the thoracic spine. Assessing vertebral bone structure may be important for preventing instrumentation failure in the upper thoracic spine, which is a potential complication of surgery. In this study, we evaluated volumetric bone mineral density, trabecular bone porosity, and cortical calcification in the cervical and upper thoracic spine using three-dimensional (3D) trabecular structure measurement software. The study included 79 patients with cervical spine disorders who underwent various surgical procedures and preoperative imaging, including dual-energy X-ray absorptiometry and computed tomography (CT) scans from C3 to Th3. Quantitative analysis using specialized software assessed volumetric bone mineral density and trabecular and cortical bone parameters, and statistical analyses were performed to examine correlations between imaging metrics and indicators of bone fragility. Two-dimensional CT evaluation revealed different trends between cancellous and cortical bone in the cervical and thoracic spine, suggesting that detailed 3D evaluation may also be important. en-copyright= kn-copyright= en-aut-name=AoyamaShingo en-aut-sei=Aoyama en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaTerumasa en-aut-sei=Ikeda en-aut-mei=Terumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NangoNobuhito en-aut-sei=Nango en-aut-mei=Nobuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotoKoji en-aut-sei=Goto en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Kindai University Hospital kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Kindai University Hospital kn-affil= affil-num=3 en-affil=Ratoc System Engineering Co., Ltd. kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Kindai University Hospital kn-affil= en-keyword=cervical spine kn-keyword=cervical spine en-keyword=volumetric bone mineral density kn-keyword=volumetric bone mineral density en-keyword=three-dimensional trabecular structure measurement kn-keyword=three-dimensional trabecular structure measurement END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=3 article-no= start-page=195 end-page=202 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=HIP COMPASS®: A Mechanical Intraoperative Navigation Guide Associated with Improved Revision-Free Implant Survivorship after Ceramic-on-Ceramic Total Hip Arthroplasty at Minimum 10-Year Follow-up en-subtitle= kn-subtitle= en-abstract= kn-abstract=HIP COMPASS® has demonstrated improved accuracy in intraoperative support for the acetabular component insertion angle. We assessed long-term revision-free implant survivorship following total hip arthroplasty (THA) using HIP COMPASS, with ≥10 years of follow-up. We retrospectively analyzed 210 hips of 186 patients who underwent cementless THA with ceramic-on-ceramic bearing couples, with or without HIP COMPASS. The mean follow-up duration was 10.8 years in the HIp COMPASS group and 12.7 years in the control group. Overall, 86.0% and 78.2% of cups were placed within Lewinnek’s safe zone with and without HIP COMPASS, respectively. Variability in radiographic inclination and anteversion was greater in the control group than in the HIP COMPASS group. Dislocation rates were 3.2% in the control group and 1.2% in the HIP COMPASS group, with no significant difference between groups. The control group had a significantly higher revision rate than the HIP COMPASS group (7.3% vs. 1.2%). Use of HIP COMPASS was associated with improved long-term revision-free implant survivorship over ≥ 10 years and more consistent acetabular component positioning at an appropriate insertion angle, which may contribute to stable initial fixation. en-copyright= kn-copyright= en-aut-name=TeiYoshiaki en-aut-sei=Tei en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ImaiNorio en-aut-sei=Imai en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraKeishi en-aut-sei=Kimura en-aut-mei=Keishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiranoYuki en-aut-sei=Hirano en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HorigomeYoji en-aut-sei=Horigome en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SudaKen en-aut-sei=Suda en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawashimaHiroyuki en-aut-sei=Kawashima en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=2 en-affil=Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=3 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=4 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=5 en-affil=Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=6 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=7 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= en-keyword=HIP COMPASS® kn-keyword=HIP COMPASS® en-keyword=survivorship kn-keyword=survivorship en-keyword=total hip arthroplasty kn-keyword=total hip arthroplasty en-keyword=ceramic-on-ceramic kn-keyword=ceramic-on-ceramic END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260617 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Age-related changes in the orbital pulley array of older Japanese adults with acquired exotropia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: To evaluate age-related changes in the orbital pulley array using magnetic resonance imaging (MRI) in older Japanese adults with acquired exotropia (XT) compared with young healthy participants (YHP).
Methods: In this retrospective cross-sectional case series, MRI images of 30 eyes from fifteen patients (age ≥ 60 years) with distance XT and no high myopia were compared with those of 14 eyes from seven YHP. Rectus muscle (RM) pulley positions relative to the globe center were assessed. The lateral rectus muscle–superior rectus (LR–SR) band was evaluated for rupture.
Results: Mean age of patients with XT was 73.7 ± 5.5 years. Compared with YHP, patients with XT showed significant inferior displacement of the lateral rectus (LR) pulley (–3.6 ± 1.2 mm vs. − 2.0 ± 1.1 mm, p < 0.01) and temporal displacement of the superior rectus (SR) pulley (–0.4 ± 1.2 mm vs. − 1.6 ± 0.8 mm, p < 0.01). No significant differences were observed in medial rectus or inferior rectus pulley positions. Inferior LR pulley displacement correlated with inferior SR pulley displacement (r = 0.41, p = 0.03), whereas no significant relationship was observed between LR pulley position and MR or IR pulley position. Rupture of the LR–SR band was observed in 24 orbits (80.0%).
Conclusion: Older Japanese adults with XT exhibit localized pulley displacement and LR–SR band rupture. These structural changes differ from the global sagging observed in sagging eye syndrome and may contribute to the pathogenesis of acquired exotropia in older adults. en-copyright= kn-copyright= en-aut-name=KonoReika en-aut-sei=Kono en-aut-mei=Reika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamasakiIchiro en-aut-sei=Hamasaki en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KishimotoFumiko en-aut-sei=Kishimoto en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShibataKiyo en-aut-sei=Shibata en-aut-mei=Kiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MorisawaShin en-aut-sei=Morisawa en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Ophthalmology,, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Lino Eye Clinic kn-affil= affil-num=3 en-affil=Division of Ophthalmology, Ibara City Hospital kn-affil= affil-num=4 en-affil=Lino Eye Clinic kn-affil= affil-num=5 en-affil=Department of Ophthalmology,, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Ophthalmology,, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=18 article-no= start-page=1675 end-page=1687 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trisomy 8 alters chromatin conformations and activates Y chromosome genes in stem cells to drive a pre-leukemic state en-subtitle= kn-subtitle= en-abstract= kn-abstract=The mechanistic role of trisomy 8 in the development of myelodysplastic syndrome (MDS) remains poorly defined. Here, we generated a trisomy 8 mouse model by transferring a human chromosome 8 into murine embryonic stem cells and prospectively examined the effects on hematopoietic stem cells (HSC) by trisomy 8. The expression of inflammatory genes was enhanced, and hematopoietic programs mediated by transcription factors and polycomb repressive complex 2 (PRC2) were dysregulated in trisomy 8 HSC, which impaired their self-renewal and balanced differentiation. Trisomy 8 HSC altered the chromatin accessibility and conformations and activated Y chromosome genes, such as Uty/Kdm6c epigenetic modifier, which is known to demethylate histone H3K27me3 modification. The Uty gene facilitated the activation of PRC2-target and Runx1-target genes in leukemogenesis and drove the proliferation of human trisomy 8 leukemic cells. Since the RUNX1 gene is frequently mutated in patients with trisomy 8 MDS, its deletion attenuated the enhanced expression of inflammatory genes and mitigated the impaired self-renewal of trisomy 8 HSC in mice. Our findings reveal that trisomy 8 altered the transcriptional programs and chromatin conformations in HSC and drove a pre-malignant state through activating the expression of Uty, suggesting a route for the development of trisomy 8 MDS. en-copyright= kn-copyright= en-aut-name=BaiJie en-aut-sei=Bai en-aut-mei=Jie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ArakiKimi en-aut-sei=Araki en-aut-mei=Kimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurotakiDaisuke en-aut-sei=Kurotaki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Eerdunduleng en-aut-sei=Eerdunduleng en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SorinSupannika en-aut-sei=Sorin en-aut-mei=Supannika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HiramatsuKei en-aut-sei=Hiramatsu en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UnoNarumi en-aut-sei=Uno en-aut-mei=Narumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HamashimaAi en-aut-sei=Hamashima en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IimoriMihoko en-aut-sei=Iimori en-aut-mei=Mihoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KikuchiKenta en-aut-sei=Kikuchi en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TerashimaMinoru en-aut-sei=Terashima en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KubotaSho en-aut-sei=Kubota en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KohrogiKensaku en-aut-sei=Kohrogi en-aut-mei=Kensaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HuangGang en-aut-sei=Huang en-aut-mei=Gang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OgawaMinetaro en-aut-sei=Ogawa en-aut-mei=Minetaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OshimuraMitsuo en-aut-sei=Oshimura en-aut-mei=Mitsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KazukiYasuhiro en-aut-sei=Kazuki en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SashidaGoro en-aut-sei=Sashida en-aut-mei=Goro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University kn-affil= affil-num=2 en-affil=Institute of Resource Development and Analysis, Kumamoto University kn-affil= affil-num=3 en-affil=Laboratory of Chromatin Organization in Immune Cell Development, International Research Center for Medical Sciences, Kumamoto University kn-affil= affil-num=4 en-affil=Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University kn-affil= affil-num=5 en-affil=Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University kn-affil= affil-num=6 en-affil=Department of Chromosome Biomedical Engineering, Integrated Medical Sciences, Graduate School of Medical Sciences, Tottori University kn-affil= affil-num=7 en-affil=Laboratory of Bioengineering, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences kn-affil= affil-num=8 en-affil=Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University kn-affil= affil-num=9 en-affil=Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University kn-affil= affil-num=10 en-affil=Laboratory of Chromatin Organization in Immune Cell Development, International Research Center for Medical Sciences, Kumamoto University kn-affil= affil-num=11 en-affil=Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University kn-affil= affil-num=12 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University kn-affil= affil-num=14 en-affil=Department of Cell Systems & Anatomy, Department of Pathology & Laboratory Medicine, UT Health San Antonio, Joe R. and Teresa Lozano Long School of Medicine, Mays Cancer Center at UT Health San Antonio kn-affil= affil-num=15 en-affil=Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University kn-affil= affil-num=16 en-affil=Chromosome Engineering Research Center, Tottori University kn-affil= affil-num=17 en-affil=Department of Chromosome Biomedical Engineering, Integrated Medical Sciences, Graduate School of Medical Sciences, Tottori University kn-affil= affil-num=18 en-affil=Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=3 article-no= start-page=e70104 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260429 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=VGLL3 Regulates DAPK2-Mediated Autophagy During Osteoblast Differentiation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vestigial-like family member 3 (VGLL3), a transcriptional cofactor of the TEA domain family, has been previously identified as a regulator of osteoblast differentiation. Building upon our previous findings, we investigated VGLL3 function in MC3T3-E1 osteoblasts using an integrated approach combining transcriptomic analysis and functional assays to identify its downstream effectors and explore associated autophagy mechanisms. RNA-seq analysis of Vgll3-knockdown (shVgll3) cells identified death-associated protein kinase 2 (DAPK2), a regulator of autophagy, as a downstream effector. Autophagic activity was examined using transmission electron microscopy and western blot analysis of LC3-II and p62 proteins. The effects of Dapk2 knockdown (shDapk2) on osteoblast differentiation were evaluated using qPCR, western blotting, alkaline phosphatase staining, and Alizarin Red staining. Rapamycin treatment was used to determine whether pharmacologic activation of autophagy could restore osteoblast function. Vgll3 knockdown significantly suppressed autophagic flux, as evidenced by fewer autophagic vacuoles, decreased LC3-II accumulation, and increased p62 expression. A comparable reduction in autophagic activity was observed in shDapk2 cells and was accompanied by impaired osteoblast differentiation. Rapamycin treatment partially restored autophagy and osteogenic differentiation in Vgll3-deficient cells. Finally, overexpression of DAPK2 partially rescued autophagic activity and osteogenic differentiation in shVgll3 cells, supporting its role as a key downstream functional effector. FOXM1 was further implicated as a potential transcriptional regulator contributing to DAPK2 expression. Collectively, our findings suggest that VGLL3 may influence osteogenic differentiation in osteoblasts, potentially involving DAPK2-associated autophagy. en-copyright= kn-copyright= en-aut-name=HeYuhan en-aut-sei=He en-aut-mei=Yuhan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WengYao en-aut-sei=Weng en-aut-mei=Yao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SitosariHeriati en-aut-sei=Sitosari en-aut-mei=Heriati kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhengYilin en-aut-sei=Zheng en-aut-mei=Yilin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=QuYaxin en-aut-sei=Qu en-aut-mei=Yaxin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkegameMika en-aut-sei=Ikegame en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamuraHirohiko en-aut-sei=Okamura en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Biology, Faculty of Dentistry, Universitas Gadjah Mada kn-affil= affil-num=5 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=autophagy kn-keyword=autophagy en-keyword=bone metabolism kn-keyword=bone metabolism en-keyword=death-associated protein kinase 2 kn-keyword=death-associated protein kinase 2 en-keyword=osteoblast differentiation kn-keyword=osteoblast differentiation en-keyword=vestigial-like 3 kn-keyword=vestigial-like 3 END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=5 article-no= start-page=ivag139 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=Lung Segmental Perfusion Defect Is Associated With Airway Complications After Living-Donor Lobar Lung Transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=PURPOSE: Airway complications (ACs) are potentially fatal after lung transplantation (LT). Although bronchial blood flow to the graft is supplied mainly from the pulmonary circulation after LT, lung segmental perfusion defects (LSPDs) are occasionally identified on lung perfusion scintigraphy (Q-scinti) after living-donor lobar LT (LDLLT). Lung segmental perfusion defects may impair bronchial healing and contribute to the development of ACs. This study aimed to evaluate the relationship between LSPD and AC after LDLLT.
METHODS: We retrospectively reviewed 86 recipients who underwent LDLLT and 163 living donors at our institution from October 1998 to December 2023. Transplanted lungs that developed AC were classified as the AC group, whereas those without AC were classified as the non-AC group. Blood flow in the transplanted lungs was evaluated using Q-scinti after LDLLT.
RESULTS: AC developed in 8 (4.9%) of 163 transplanted lungs after LDLLT. Although there were no significant differences in recipient-related variables between the 2 groups, LSPD was detected significantly more frequently in the AC group (n = 8) than in the non-AC group (n = 155) (50.0% vs 6.5%, P = .002). Furthermore, transplanted lungs showing LSPD were associated with significantly higher grades of the pulmonary interlobar fissures at the time of living-donor lobectomy (P = .025). Overall survival did not differ between patients with and without AC after LDLLT.
CONCLUSIONS: LSPD on Q-scinti, which may develop in grafts with incomplete interlobar fissures during living-donor lobectomy, is associated with the development of AC after LDLLT.
CLINICAL REGISTRATION NUMBER: This study was approved by the Institutional Review Board of Okayama University Hospital (approval date: August 23, 2024; 2409-027). en-copyright= kn-copyright= en-aut-name=ImanishiKentaro en-aut-sei=Imanishi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RyukoTsuyoshi en-aut-sei=Ryuko en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=airway complication kn-keyword=airway complication en-keyword=interlobar fissure kn-keyword=interlobar fissure en-keyword=living-donor lobar lung transplantation kn-keyword=living-donor lobar lung transplantation en-keyword=lung perfusion scintigraphy kn-keyword=lung perfusion scintigraphy en-keyword=lung transplantation kn-keyword=lung transplantation 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=17 cd-vols= no-issue=3 article-no= start-page=102635 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Epidemiological and molecular characteristics of human-biting ticks in areas endemic to Japanese spotted fever: a prospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tick-borne diseases (TBDs) have become a great health concern worldwide. This study aimed to clarify the pathogenic and potentially pathogenic microorganisms carried by ticks that bite humans and to assess the risk of acquiring tick-borne infections in regions endemic for Japanese spotted fever. Tick specimens were prospectively collected from patients who presented with tick bites at 10 medical institutions in the Hiroshima, Okayama, and Kagawa prefectures, Japan between May 2023 and December 2024. The evaluated parameters included the estimated bite location, date of bite, patient age, tick species identification, and presence of TBD-associated pathogens in the collected ticks. Overall, 191 ticks were collected from 181 patients. Among patients with known sex, females were slightly more prevalent than males, and 45.9% of the patients were aged ≥ 70 years. Seasonal distribution demonstrated a peak incidence from April to July, with the highest number of cases observed in June (29.3%). Amblyomma testudinarium was the predominant species, accounting for 152 (79.6%) ticks, followed by Haemaphysalis hystricis (7.3%) and Haemaphysalis longicornis (6.8%). Nymphs represented the majority (83.8%), whereas adults and larvae accounted for 14.6% and 1.0%, respectively. A total of 27 ticks (14.1%) carried Rickettsia species, including two identified species (Rickettsia tamurae and Rickettsia monacensis) and one unclassified Rickettsia species. However, molecular analysis did not detect any known human pathogenic organisms, including Ehrlichia and Anaplasma species, Francisella tularensis, or Rickettsia japonica. Further epidemiological data regarding the abundance of tick-borne pathogens will provide valuable surveillance information with significant clinical utility for disease diagnosis and management. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SunamiHiroshi en-aut-sei=Sunami en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanoYasuhiro en-aut-sei=Nakano en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamotoKenta en-aut-sei=Nakamoto en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkazawaHidemasa en-aut-sei=Akazawa en-aut-mei=Hidemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HidaniYoshimi en-aut-sei=Hidani en-aut-mei=Yoshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KidaKouji en-aut-sei=Kida en-aut-mei=Kouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsurumiGo en-aut-sei=Tsurumi en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Sumiyoshi Fujii Hospital kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Numakuma Hospital kn-affil= affil-num=7 en-affil=Okayama Prefectural Institute for Environmental Science and Public Health kn-affil= affil-num=8 en-affil=Okayama Prefectural Institute for Environmental Science and Public Health kn-affil= affil-num=9 en-affil= kn-affil= en-keyword=Epidemiology kn-keyword=Epidemiology en-keyword=Japanese spotted fever kn-keyword=Japanese spotted fever en-keyword=Rickettsia species kn-keyword=Rickettsia species en-keyword=Tick bite kn-keyword=Tick bite en-keyword=Tick-borne disease kn-keyword=Tick-borne disease END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=5 article-no= start-page=4118 end-page=4121 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel Arterial Reconstruction of the Left Gastric Artery Supplying the Replaced Left Hepatic Artery in Distal Pancreatectomy with Celiac Axis Resection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background. Distal pancreatectomy with celiac axis resection (DP-CAR) with reconstruction of the left gastric artery (LGA) is a technically challenging procedure. The middle colic artery is commonly used for LGA reconstruction. This study highlights our novel arterial reconstruction of the LGA using the common hepatic artery (CHA) supplying the replaced left hepatic artery (rLHA) during DP-CAR.
Patient and Methods. A 65-year-old man diagnosed with locally advanced unresectable pancreatic body cancer underwent DP-CAR following systemic chemotherapy. As a rLHA arising from the LGA was present, arterial reconstruction was necessary.
Results. After confirming resectability, the CHA and LGA were encircled. Following division of the pancreas and radical lymphadenectomy, the origin of the celiac axis (CA) was divided. Subsequently, the CHA and LGA were transected and anastomosed. An indocyanine green fluorescence system was used to confirm adequate arterial blood supply and satisfactory tissue perfusion. Operative time was 215 min, with an estimated blood loss of 35 mL.
Conclusions. This study demonstrated a novel arterial reconstruction of the LGA supplying the rLHA during DP-CAR. The CHA may be a candidate for the reconstruction of the LGA in DP-CAR. en-copyright= kn-copyright= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoAtene en-aut-sei=Ito en-aut-mei=Atene kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiyamaTakeyoshi en-aut-sei=Nishiyama en-aut-mei=Takeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YokoyamaShohei en-aut-sei=Yokoyama en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Distal pancreatectomy with celiac axis resection kn-keyword=Distal pancreatectomy with celiac axis resection en-keyword=Arterial reconstruction kn-keyword=Arterial reconstruction en-keyword=Pancreatic cancer kn-keyword=Pancreatic cancer END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=1 article-no= start-page=97 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260424 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Navigating long-term patient-reported outcomes after colorectal cancer surgery in older adults: ostomy, nutritional status, and living conditions as determinants in a prospective cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose To elucidate determinants of long-term patient-reported outcomes (PROs) following colorectal cancer (CRC) surgery in older adults, focusing on the impact of ostomy creation, nutritional status, and living conditions on functional independence and quality of life (QoL).
Methods This single-center, prospective observational study included patients aged ≥ 75 years who underwent elective CRC resection between July 2020 and December 2023. Comprehensive geriatric assessments were performed preoperatively, and PROs—including Instrumental Activities of Daily Living (IADL), EQ-5D, and EQ-VAS—were reassessed more than one year postoperatively. The primary outcomes were postoperative changes in IADL and QoL. Modified Poisson regression identified independent determinants of long-term decline in each PRO domain.
Results Sixty patients (median age 79 years; 60% female) completed one-year follow-up. IADL declined in 35.6% of patients, EQ-5D in 26.6%, and EQ-VAS in 43.3%. Multivariate analysis revealed that stoma formation was independently associated with IADL decline (adjusted RR = 3.37, 95% CI 1.50–7.54, p = 0.003), whereas living alone postoperatively correlated with preserved IADL (adjusted RR = 0.14, 95% CI 0.02–0.87, p = 0.035). Low preoperative BMI (< 20 kg/m2) was significantly associated with EQ-5D deterioration (adjusted RR = 5.25, 95% CI 1.20–22.94, p = 0.027). No significant predictors were identified for EQ-VAS decline.
Conclusion Among older CRC patients, stoma creation predicts long-term functional decline, while low BMI predicts QoL deterioration. Conversely, independent living appears protective for functional maintenance. Integrating PROs into perioperative assessment and tailoring surgical, nutritional, and social interventions may enhance survivorship outcomes in this aging population. en-copyright= kn-copyright= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItagakiShiori en-aut-sei=Itagaki en-aut-mei=Shiori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TamuraRie en-aut-sei=Tamura en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuokaYoshikazu en-aut-sei=Matsuoka en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KondoYoshitaka en-aut-sei=Kondo en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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 Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Perioperative Management Center, Okayama University Hospital kn-affil= affil-num=3 en-affil=Center for Innovative Clinical Medicine, Medical Development Field, Okayama University kn-affil= affil-num=4 en-affil=Perioperative Management Center, Okayama University Hospital kn-affil= affil-num=5 en-affil=Perioperative Management Center, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= en-keyword=Colorectal cancer kn-keyword=Colorectal cancer en-keyword=Older patients kn-keyword=Older patients en-keyword=Patient-reported outcomes kn-keyword=Patient-reported outcomes en-keyword=Quality of life kn-keyword=Quality of life en-keyword=Surgery kn-keyword=Surgery END start-ver=1.4 cd-journal=joma no-vol=40 cd-vols= no-issue=1 article-no= start-page=349 end-page=354 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=Modified Subtraction Technique for the Middle Hepatic Vein Tributary and Glissonean Pedicle in Right Lobe Graft Procurement en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: The procurement of right lobe grafts while preserving the middle hepatic vein (MHV) tributaries (V5 and V8) just before graft retrieval is technically challenging. Moreover, the safe isolation of the hepatic duct from the Glissonean pedicle is essential in living donor hepatectomy. To date, few studies have reported surgical techniques for preserving the MHV tributaries during right lobe graft procurement.
Patients and Methods: This report presents our modified subtraction technique for managing the MHV tributaries and Glissonean pedicle during right lobe graft procurement. First, a subtraction technique for the MHV tributaries was initiated by isolating the right Glissonean pedicle. The lower tip of the tape was placed behind the caudate lobe and passed behind the right hepatic vein. Each end of the tape was then passed behind V5 and V8, followed by dissection of the remaining liver parenchyma between them. Subsequently, a subtraction technique for the Glissonean pedicle was applied to safely isolate the right hepatic duct and hilar plate.
Results: Between September 2011 and May 2025, seven donors underwent right lobe graft procurement using the subtraction technique for the middle hepatic vein tributaries. The mean operative time was 381 min with an estimated blood loss of 217 ml. Using the subtraction technique, all middle hepatic vein tributaries were preserved just before graft retrieval.
Conclusion: This study presents subtraction techniques used during living donor hepatectomy. The technique may facilitate liver parenchyma dissection while preserving MHV tributaries just before graft retrieval and isolating the Glissonean pedicle. en-copyright= kn-copyright= en-aut-name=TAKAGIKOSEI en-aut-sei=TAKAGI en-aut-mei=KOSEI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FUJITOMOKAZU en-aut-sei=FUJI en-aut-mei=TOMOKAZU kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YASUIKAZUYA en-aut-sei=YASUI en-aut-mei=KAZUYA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NISHIYAMATAKEYOSHI en-aut-sei=NISHIYAMA en-aut-mei=TAKEYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NAGAIYASUO en-aut-sei=NAGAI en-aut-mei=YASUO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YOKOYAMASHOHEI en-aut-sei=YOKOYAMA en-aut-mei=SHOHEI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UMEDAYUZO en-aut-sei=UMEDA en-aut-mei=YUZO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FUJIWARATOSHIYOSHI en-aut-sei=FUJIWARA en-aut-mei=TOSHIYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hepatobiliary Pancreatic Surgery, Ehime University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Subtraction kn-keyword=Subtraction en-keyword=tape repositioning kn-keyword=tape repositioning en-keyword=middle hepatic vein kn-keyword=middle hepatic vein en-keyword=donor procurement kn-keyword=donor procurement END start-ver=1.4 cd-journal=joma no-vol=40 cd-vols= no-issue=3 article-no= start-page=1570 end-page=1576 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260428 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Donor Cirrhosis Outcome Risk Estimator (CORE) Score on Recipient Outcomes Following Living-donor Liver Transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Several studies have investigated predictive factors for outcomes of living-donor liver transplantation (LDLT). However, few have examined the clinical significance of the Cirrhosis Outcome Risk Estimator (CORE) score on prognosis following LDLT. This study aimed to investigate the impact of donor CORE scores in predicting the outcomes of patients undergoing LDLT.
Patients and Methods: This single-center retrospective study included 362 adult LDLT recipients at our Institution between January 1998 and December 2024. Patient and graft survival rates were compared between the groups with low (≤0.05) and high (>0.05) CORE scores. Subsequently, multivariate analyses were performed to investigate prognostic factors for survival, including the CORE score.
Results: Patients in the group with a low CORE score had significantly better survival (p=0.001; 5-year, 85.3% vs. 76.2%) and graft survival (p=0.001; 5-year, 84.1% vs. 74.6%) than those with a high CORE score. Multivariate analyses identified the CORE score (>0.05) as an independent predictor of patient survival (hazard ratio=1.70, 95% confidence interval=1.01-2.62, p=0.018) and graft survival (hazard ratio=1.66, 95% confidence interval=1.07-2.57, p=0.024).
Conclusion: This study demonstrated the clinical significance of donor CORE scores in recipient outcomes after LDLT. Assessment of the donor CORE score may be useful for evaluating the quality of liver grafts and estimating recipient outcomes. en-copyright= kn-copyright= en-aut-name=TAKAGIKOSEI en-aut-sei=TAKAGI en-aut-mei=KOSEI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FUJITOMOKAZU en-aut-sei=FUJI en-aut-mei=TOMOKAZU kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YASUIKAZUYA en-aut-sei=YASUI en-aut-mei=KAZUYA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NISHIYAMATAKEYOSHI en-aut-sei=NISHIYAMA en-aut-mei=TAKEYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NAGAIYASUO en-aut-sei=NAGAI en-aut-mei=YASUO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OKADANAOHIRO en-aut-sei=OKADA en-aut-mei=NAOHIRO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YOKOYAMASHOHEI en-aut-sei=YOKOYAMA en-aut-mei=SHOHEI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FUJIWARATOSHIYOSHI en-aut-sei=FUJIWARA en-aut-mei=TOSHIYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Living-donor liver transplantation kn-keyword=Living-donor liver transplantation en-keyword=donor kn-keyword=donor en-keyword=recipient kn-keyword=recipient en-keyword=survival outcomes kn-keyword=survival outcomes en-keyword=Cirrhosis Outcome Risk Estimator score kn-keyword=Cirrhosis Outcome Risk Estimator score en-keyword=CORE kn-keyword=CORE END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=22 article-no= start-page=3694 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognosis Prediction Model After Upfront Surgery for Resectable Pancreatic Ductal Adenocarcinoma: A Multicenter Study (OS-HBP-2) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Upfront surgery (UFS) remains the standard treatment for patients with resectable pancreatic ductal adenocarcinoma (PDAC). We aimed to investigate the prognostic factors for survival after UFS in patients with resectable PDAC and to develop a prognostic prediction model. Methods: This multicenter, retrospective study included 603 patients who underwent UFS for resectable PDAC between January 2013 and December 2017. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival (OS). We constructed a prognostic prediction model for OS after UFS. An internal validation was performed to evaluate the discriminative performance of the model. Results: The 1-, 3-, and 5-year OS rates were 83.7%, 48.2%, and 37.5%, respectively. The Cox proportional hazards model showed that tumor size > 2 cm (hazard ratio [HR] 1.50, p = 0.001); tumor contact with the portal and superior mesenteric veins of ≤180° (HR 1.47, p = 0.003); carbohydrate antigen 19-9 levels of 40 to 500 U/mL (HR 1.59, p = 0.002) and ≥500 U/mL (HR 2.16, p < 0.001); and a modified Glasgow Prognostic Score of two (HR 1.56, p = 0.038) were predictors associated with OS. The prognostic prediction model for 5-year OS demonstrated an area under the curve of 0.68. The calibration plots indicate a concordance index of 0.63. Conclusions: We identified the preoperative prognostic factors for OS and developed a prognostic prediction model to estimate OS in patients undergoing UFS for resectable PDAC. Our model may be useful and internally validated for predicting OS. en-copyright= kn-copyright= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiokiMasayoshi en-aut-sei=Hioki en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkabayashiTakehiro en-aut-sei=Okabayashi en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KojimaToru en-aut-sei=Kojima en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EndoYoshikatsu en-aut-sei=Endo en-aut-mei=Yoshikatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NobuokaDaisuke en-aut-sei=Nobuoka en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SuiKenta en-aut-sei=Sui en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=InagakiMasaru en-aut-sei=Inagaki en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShinouraSusumu en-aut-sei=Shinoura en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KimuraMasashi en-aut-sei=Kimura en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsudaTatsuo en-aut-sei=Matsuda en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AokiHideki en-aut-sei=Aoki en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Surgery, Fukuyama City Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Surgery, Okayama Saiseikai General Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Himeji Red Cross Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, Fukuyama City Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, Kagawa Prefectural Hospital kn-affil= affil-num=10 en-affil=Department of Surgery, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=11 en-affil=Department of Surgery, Tsuyama Chuo Hospital kn-affil= affil-num=12 en-affil=Department of Surgery, Matsuyama Shimin Hospital kn-affil= affil-num=13 en-affil=Department of Surgery, Tenwakai Matsuda Hospital kn-affil= affil-num=14 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=pancreatic cancer kn-keyword=pancreatic cancer en-keyword=resectable kn-keyword=resectable en-keyword=upfront Surgery kn-keyword=upfront Surgery en-keyword=outcomes kn-keyword=outcomes END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=6 article-no= start-page=e72814 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260525 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CPPD-Induced Iliopsoas Bursitis Mimicking Pyomyositis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Calcium pyrophosphate deposition disease may mimic an iliopsoas abscess on imaging. The combined use of polarized light microscopy and 16S rRNA gene analysis can help distinguish crystal-induced inflammation from infection, thereby preventing unnecessary antimicrobial therapy. en-copyright= kn-copyright= en-aut-name=OkunobuHiroki en-aut-sei=Okunobu en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=16S rRNA kn-keyword=16S rRNA en-keyword=abscess kn-keyword=abscess en-keyword=calcium pyrophosphate deposition disease kn-keyword=calcium pyrophosphate deposition disease en-keyword=culture-negative kn-keyword=culture-negative en-keyword=direct sequencing analysis kn-keyword=direct sequencing analysis END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=10 article-no= start-page=3702 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exploratory Analysis of Serum IGF-I Levels and Symptom Trajectories in Long COVID During the Omicron Period en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Although several risk factors have been reported for long COVID (LC), reliable biomarkers for this illness remain lacking. Insulin-like growth factor (IGF)-I, a major mediator of growth hormones, plays an important role in metabolism, neuroprotection, and systemic homeostasis, and therefore may be useful in predicting the severity and prognosis of LC. Methods: This study included patients who visited a specialized clinic for long COVID between 2022 and 2025 during the Omicron period and had serum IGF-I measurements taken. IGF-I levels were expressed as age- and sex-adjusted standard deviation scores (IGF-I SD), and patients were classified into low (SD < −1.0), normal (−1.0 ≤ SD < 1.0), and high (SD ≥ 1.0) groups. Clinical characteristics, patient-reported outcomes, laboratory data, and follow-up duration were analyzed. Results: A total of 811 patients were included (median 42 years; 52.5% female). Compared with the normal group, the low-IGF-I group exhibited higher fatigue (FAS: 37.0 vs. 34.0; p < 0.05) and depressive (SDS: 50.0 vs. 49.0; p < 0.05) status. Multivariable linear regression analyses identified lower IGF-I SD as independently associated with higher scores of both FAS and SDS. IGF-I SD values showed negative correlations with ferritin (ρ = −0.125, p < 0.05) and TSH (ρ = −0.202, p < 0.01) and positive correlations with albumin (ρ = 0.227, p < 0.01) and FT4 (ρ = 0.165, p < 0.01). Among the 237 patients who completed follow-up, the median duration from the initial visit to recovery tended to be longer in the low-IGF-I group (221 days) compared with the normal (191 days) and high (109 days) groups, although these differences were not statistically significant overall. In patients aged < 50 years, the low-IGF-I group showed a relatively longer follow-up duration (p < 0.05). Furthermore, the low-IGF-I group had a longer time to recovery compared to the high-IGF-I group (p < 0.05), and this difference was more pronounced in patients under 50 years of age, with significant differences observed among the three IGF-I groups. Conclusions: Lower IGF-I levels in LC may be associated with greater fatigue and depressive symptoms and longer recovery time, particularly in younger patients. Further studies are needed to clarify the clinical significance of these findings. en-copyright= kn-copyright= en-aut-name=SuyamaAtsuhito en-aut-sei=Suyama en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=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=TokumasuKazuki en-aut-sei=Tokumasu en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 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=8 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=9 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=10 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=11 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=12 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=13 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=14 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= en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=fatigue kn-keyword=fatigue en-keyword=IGF-I kn-keyword=IGF-I en-keyword=long COVID kn-keyword=long COVID en-keyword=recovery kn-keyword=recovery END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue= article-no= start-page=1774957 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=Hochuekkito attenuates anxiety-like behavior associated with pulmonary inflammation induced by intratracheal lipopolysaccharides in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: We have previously demonstrated that intratracheal lipopolysaccharide (LPS) injection induces significant pulmonary inflammation accompanied by hippocampal microglial activation, indicative of neuroinflammation. Hochuekkito (HET) is a traditional Japanese herbal medicine used to treat various conditions, including mental disorders and physical weakness. We have previously reported that HET ameliorates anxiety-like behaviors induced by intraperitoneal LPS injections in mice. However, its anxiolytic effects on anxiety-like behaviors due to pulmonary inflammation remain poorly understood. Therefore, in the present study, we aimed to investigate the effects of HET on anxiety-like behaviors induced by intratracheal LPS injection in mice.
Methods: Mice received HET (1.0 g/kg) once daily for 2 weeks through oral gavage prior to LPS treatment. The light-dark box test was conducted 24 h following LPS injection to assess anxiety-like behaviors. Diazepam, a clinically used anxiolytic, served as a positive control. The lung wet-to-dry weight ratio was determined, and the concentrations of interleukin-6 (IL-6) in the lungs and serum were assessed.
Results: Repeated administration of HET prevented the development of anxiety-like behaviors and reduced serum IL-6 concentrations and hippocampal Il6 mRNA expression levels in LPS-treated mice. Diazepam failed to exert significant effects in LPS-treated mice, whereas HET remained effective under inflammatory conditions. Moreover, LPS injections significantly increased the number of Iba-1-immunoreactive microglial cells in the CA1 region of the hippocampus, whereas this effect was suppressed by treatment with HET. In the bronchoalveolar lavage fluid (BALF), the LPS-induced increase in white blood cell count was significantly reduced by treatment with HET. Furthermore, HET alleviated LPS-induced pulmonary inflammation, as evidenced by decreased lung wet-to-dry weight ratios.
Conclusion: This study suggests that inflammation induced by intratracheal LPS injection contributes to anxiety-like behaviors in mice and that IL-6 may play a key role in linking peripheral inflammation to neuroinflammatory responses. The anxiolytic effects of HET appear to be associated, at least in part, with the suppression of IL-6 elevation in both the periphery and the hippocampus, along with attenuation of microglial activation. Our findings suggest that HET may serve as a potential therapeutic agent for anxiety-like behaviors associated with pulmonary inflammation. en-copyright= kn-copyright= en-aut-name=IzushiYasuhisa en-aut-sei=Izushi en-aut-mei=Yasuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UshioSoichiro en-aut-sei=Ushio en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UedaTeppei en-aut-sei=Ueda en-aut-mei=Teppei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TasakaYuichi en-aut-sei=Tasaka en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KitamuraYoshihisa en-aut-sei=Kitamura en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pharmacotherapy, Graduate School of Pharmacy, Shujitsu University kn-affil= affil-num=2 en-affil=Department of Pharmaceutical Sciences for Health Crisis Management, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=3 en-affil=Department of Pharmacotherapy, Graduate School of Pharmacy, Shujitsu University kn-affil= affil-num=4 en-affil=Laboratory of Clinical Pharmacy, School of Pharmacy, Shujitsu University kn-affil= affil-num=5 en-affil=Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pharmacotherapy, Graduate School of Pharmacy, Shujitsu University kn-affil= en-keyword=anxiety kn-keyword=anxiety en-keyword=hochuekkito kn-keyword=hochuekkito en-keyword=inflammation kn-keyword=inflammation en-keyword=interleukin-6 kn-keyword=interleukin-6 en-keyword=lipopolysaccharide kn-keyword=lipopolysaccharide en-keyword=lung kn-keyword=lung en-keyword=traditional Japanese herbal medicine kn-keyword=traditional Japanese herbal medicine END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Classification of hypotony maculopathy based on optical coherence tomography findings and risk factors for visual outcomes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose To classify hypotony maculopathy (HM) using optical coherence tomography (OCT) findings and to investigate the associations among morphological types, clinical factors, and visual outcomes.
Methods We retrospectively reviewed 60 eyes that developed HM after trabeculectomy. HM was classified according to the distribution and configuration of chorioretinal undulations on OCT B-scans. Between-group comparisons were performed, and factors associated with the morphological classification and logMAR best-corrected visual acuity (BCVA) at 3 months after HM onset (3-month BCVA) were determined.
Results HM was classified into three OCT-based types by categorizing chorioretinal undulations as folds (U-shaped troughs) or spikes (V-shaped troughs): Type 1, folds only on vertical scans; Type 2, folds on both vertical and horizontal scans; Type 3, folds on both scans, with spikes. Axial length in Type 3 was significantly longer than that in Type 2 (P = 0.034). Subfoveal choroidal thickness was significantly thinner in Type 3 than in Types 1 and 2 (both P < 0.001). Minimum intraocular pressure (IOP) was significantly higher in Type 1 than in Types 2 and 3 (P < 0.001 and P = 0.003, respectively), with no difference between Types 2 and 3. In multivariable analysis using Type 1 as the reference group, minimum IOP was significantly associated with Type 2 (P = 0.001). For Type 3, both minimum IOP (P = 0.03) and subfoveal choroidal thickness (P = 0.02) showed significant associations. The 3-month BCVA was significantly worse in Type 3 than in Types 1 and 2 (P < 0.001 and P = 0.007, respectively). Chorioretinal spikes and preoperative BCVA were significantly associated with 3-month BCVA (both P < 0.001). Exploratory receiver operating characteristic analysis assessed the discriminative ability of subfoveal choroidal thickness for the presence of chorioretinal spikes (AUC = 0.876). A thickness of 195.0 μm was identified as a candidate cutoff value (sensitivity 92.3% and specificity 72.3%).
Conclusions In HM following TLE, chorioretinal spikes and preoperative BCVA are significantly associated with the 3-month BCVA. In HM, a thin subfoveal choroid (< 195.0 μm), may be associated with chorioretinal spikes, suggesting the need for careful postoperative IOP and OCT monitoring. en-copyright= kn-copyright= en-aut-name=KanzakiYuki en-aut-sei=Kanzaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMiyuki en-aut-sei=Fujiwara en-aut-mei=Miyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiwaraRie en-aut-sei=Fujiwara en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkamotoSara en-aut-sei=Okamoto en-aut-mei=Sara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MitsuiNaruka en-aut-sei=Mitsui en-aut-mei=Naruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HosokawaMio Morizane en-aut-sei=Hosokawa en-aut-mei=Mio Morizane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HayashiJunko en-aut-sei=Hayashi en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MasudaYuki en-aut-sei=Masuda en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AkatsukaRiku en-aut-sei=Akatsuka en-aut-mei=Riku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TsujiAkihiro en-aut-sei=Tsuji en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Hypotony maculopathy kn-keyword=Hypotony maculopathy en-keyword=Optical coherence tomography kn-keyword=Optical coherence tomography en-keyword=Trabeculectomy kn-keyword=Trabeculectomy en-keyword=Chorioretinal spike kn-keyword=Chorioretinal spike en-keyword=Choroidal thickness kn-keyword=Choroidal thickness en-keyword=Visual outcomes kn-keyword=Visual outcomes END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=3 article-no= start-page=104848 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Predictors of therapeutic response and pain after near-infrared photoimmunotherapy in head and neck cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Near-infrared photoimmunotherapy (NIR-PIT) has been approved by the Japanese national health insurance for approximately five years, and clinical experience has steadily accumulated. However, reports analyzing treatment outcomes and pain-related factors remain limited. This study aimed to identify predictors of therapeutic response and pain following NIR-PIT.
Methods: This retrospective cohort study included 25 patients who underwent NIR-PIT for head and neck cancer between January 2021 and June 2025. Lesion diameter and thickness were evaluated in relation to complete response (CR), and the frequency and predictors of post-treatment pain were assessed.
Results: Among 22 evaluable patients, eight achieved CR. Lesions with a shorter longest diameter and thinner thickness were significantly associated with higher CR rates (p = 0.011 and p = 0.024). Moderate-to-severe pain (Numerical Rating Scale ≥4) occurred in 18 of 48 treatment cycles (37.5%) but was significantly less frequent in patients with a history of reconstructive surgery (p = 0.017).
Conclusions: NIR-PIT demonstrated particularly favorable efficacy for short, thin lesions, suggesting that early introduction of treatment may be associated with improved therapeutic outcomes. A history of reconstructive surgery was associated with reduced post-treatment pain, highlighting the importance of individualized treatment and pain management strategies in head and neck cancer patients undergoing NIR-PIT. en-copyright= kn-copyright= en-aut-name=MatsumotoJunya en-aut-sei=Matsumoto en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MakinoTakuma en-aut-sei=Makino en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NaoiYuto en-aut-sei=Naoi en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujimotoShohei en-aut-sei=Fujimoto en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Near-infrared photoimmunotherapy kn-keyword=Near-infrared photoimmunotherapy en-keyword=Head and neck cancer kn-keyword=Head and neck cancer en-keyword=Treatment response kn-keyword=Treatment response en-keyword=Tumor size kn-keyword=Tumor size en-keyword=Tumor thickness kn-keyword=Tumor thickness en-keyword=Pain kn-keyword=Pain END start-ver=1.4 cd-journal=joma no-vol=2026 cd-vols= no-issue=1 article-no= start-page=8863202 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Selective ARID1A Loss Restricted to the Undifferentiated Component of a Mismatch Repair‐Deficient Gastric Carcinoma: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mismatch repair-deficient (dMMR) gastric carcinomas often harbor ARID1A alteration, but a sharply demarcated undifferentiated/rhabdoid component with selective ARID1A loss is uncommon and may create a diagnostic dilemma. An 80-year-old man underwent esophagogastroduodenoscopy for anemia, which revealed a circumferential Borrmann Type 3 lesion in the gastric body, and distal gastrectomy was performed. Histologically, the tumor was composed predominantly of undifferentiated carcinoma with focal rhabdoid features and a minute well-differentiated adenocarcinoma component, with an abrupt transition between the two. Immunohistochemistry showed loss of nuclear MLH1 and PMS2 in both components, whereas loss of ARID1A expression was confined to the undifferentiated component; SMARCB1 (INI1), SMARCA2 (BRM), and SMARCA4 (BRG1) were retained. EBER in situ hybridization was negative. Because gene-level testing, MSI testing, and MLH1 promoter methylation analysis were not performed, the molecular basis of the dMMR phenotype and ARID1A loss could not be determined. The restricted scope of molecular testing limits the ability to draw broad or generalizable conclusions and to fully establish clinicopathological correlations. The value of this report is, therefore, not mechanistic proof but recognition of a practical morphologic-immunophenotypic observation: When a gastric carcinoma shows a sharply demarcated shift from differentiated to undifferentiated/rhabdoid morphology, dMMR should be considered, and selective ARID1A loss in the undifferentiated component may be associated with dedifferentiation. These findings should be interpreted with caution as preliminary, hypothesis-generating observations that require validation in larger studies with more extensive molecular profiling. en-copyright= kn-copyright= en-aut-name=OmoteRika en-aut-sei=Omote en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamanoRyosuke en-aut-sei=Hamano en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaShinya en-aut-sei=Otsuka en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Diagnostic Pathology, NHO Fukuyama Medical Center kn-affil= affil-num=2 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=3 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pathology, Okayama University Hospital kn-affil= en-keyword=ARID1A kn-keyword=ARID1A en-keyword=carcinoma kn-keyword=carcinoma en-keyword=DNA mismatch repair deficiency kn-keyword=DNA mismatch repair deficiency en-keyword=rhabdoid features kn-keyword=rhabdoid features en-keyword=stomach neoplasms kn-keyword=stomach neoplasms en-keyword=SWI/SNF complex kn-keyword=SWI/SNF complex en-keyword=undifferentiated kn-keyword=undifferentiated END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=3 article-no= start-page=528 end-page=536 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical complete response and predictive factors in HER2-positive early breast cancer treated with neoadjuvant chemotherapy aimed at omission of surgery: an exploratory analysis of the JCOG1806 trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose The JCOG1806 trial (jRCTs031190129) is underway to evaluate the omission of surgery in patients with human epidermal growth factor receptor (HER2)-positive early breast cancer who have a clinical complete response (cCR) after primary systemic therapy (PST). We aimed to assess the cCR rate in this trial and identify predictive factors.
Methods HER2-positivity was defined as an immunohistochemistry (IHC) score of 3 + or in situ hybridization-positivity. A cCR was defined as the absence of detectable lesions upon palpation, contrast-enhanced magnetic resonance imaging, and ultrasonography; biopsy-based confirmation was optional in hormone receptor (HR)-negative cases and mandatory in HR-positive cases. Multivariate logistic regression analyses were used to identify predictors of a cCR.
Results The cCR rate was 57.6% (196/340 patients; 95% confidence interval [CI]: 52.2–63.0%). Strongly estrogen-receptor (ER)-positive tumors (≥ 10%) were significantly less likely to have a cCR than ER-negative tumors (odds ratio [OR], 0.41; 95% CI: 0.20–0.81). IHC 3 + tumors had higher cCR rates than IHC 1 + or 2 + tumors (OR, 2.19; 95% CI: 1.01–4.74). Compared with histological grade I tumors, cCR odds were higher in grade II (OR: 2.92; 95% CI: 1.07–7.93) and III (OR: 4.90; 95% CI: 1.76–13.7) tumors. Among patients without a cCR patients undergoing surgery, 22.2% were diagnosed with ypT0 tumors upon analysis of surgical specimens.
Conclusion ER-negativity, an IHC score of 3 + , and a higher histological grade were independent predictors of a cCR. Identifying these features may improve the feasibility and safety of surgery omission for patients with HER2-positive early breast cancer. en-copyright= kn-copyright= en-aut-name=ShigematsuHideo en-aut-sei=Shigematsu en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujisawaTomomi en-aut-sei=Fujisawa en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwataHiroji en-aut-sei=Iwata en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshibaToshiyuki en-aut-sei=Ishiba en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OzakiYukinori en-aut-sei=Ozaki en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakaiTakehiko en-aut-sei=Sakai en-aut-mei=Takehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SagaraYasuaki en-aut-sei=Sagara en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimomuraAkihiko en-aut-sei=Shimomura en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SudoKazuki en-aut-sei=Sudo en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TerataKaori en-aut-sei=Terata en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NaitoYoichi en-aut-sei=Naito en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NozawaKazuki en-aut-sei=Nozawa en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SasakiKeita en-aut-sei=Sasaki en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MitomeNoriko en-aut-sei=Mitome en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SadachiRyo en-aut-sei=Sadachi en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ShibataTaro en-aut-sei=Shibata en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University Hospital kn-affil= affil-num=2 en-affil=Gunma Prefectural Cancer Center kn-affil= affil-num=3 en-affil=Aichi Cancer Center kn-affil= affil-num=4 en-affil=Graduate School of Medical Sciences, Nagoya City University kn-affil= affil-num=5 en-affil=Institute of Science Tokyo Hospital kn-affil= affil-num=6 en-affil=Cancer Institute Hospital of the Japanese Foundation for Cancer Research kn-affil= affil-num=7 en-affil=Cancer Institute Hospital of the Japanese Foundation for Cancer Research kn-affil= affil-num=8 en-affil=Hakuaikai Sagara Hospital kn-affil= affil-num=9 en-affil=National Center for Global Health and Medicine kn-affil= affil-num=10 en-affil=National Cancer Center Hospital kn-affil= affil-num=11 en-affil=Akita University Hospital kn-affil= affil-num=12 en-affil=National Cancer Center Hospital East kn-affil= affil-num=13 en-affil=Graduate School of Medical Sciences, Nagoya City University kn-affil= affil-num=14 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=15 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=16 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=17 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=18 en-affil=Okayama University Hospital kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Primary systemic therapy kn-keyword=Primary systemic therapy en-keyword=HER2 kn-keyword=HER2 en-keyword=cCR kn-keyword=cCR en-keyword=Omission of surgery kn-keyword=Omission of surgery END start-ver=1.4 cd-journal=joma no-vol=208 cd-vols= no-issue=6 article-no= start-page=2124 end-page=2133 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260415 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Decreased renal function predicts severe cytokine release syndrome after CAR-T-cell therapy for large B-cell lymphoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cytokine release syndrome (CRS) remains a major toxicity of chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL), and robust pre-infusion predictors are needed for risk-adapted management. We retrospectively analysed LBCL patients in the Japanese nationwide registry who underwent CD19 CAR-T-cell therapy between 2019 and 2024. Among 900 patients (median age 62 years), cumulative incidences of CRS within 30 days after infusion were 75.0% for any grade, 20.8% for grade ≥ 2 and 14.0% for grade ≥ 3. In multivariable analysis, lower estimated glomerular filtration rate (eGFR) (adjusted hazard ratio [aHR] 1.108 per 10 mL/min per 1.73 m2 decrease; 95% confidence interval [CI] 1.015–1.209; p = 0.022), higher ferritin (aHR 1.006 per 100 ng/mL; 95% CI 1.001–1.010; p = 0.016), C-reactive protein (CRP) (aHR 1.142 per mg/dL; 95% CI 1.091–1.195; p < 0.001) and lactate dehydrogenase (LDH) (aHR 1.073 per 100 U/L; 95% CI 1.008–1.142; p = 0.028) independently predicted grade ≥ 2 CRS. We then built a four-factor CRS pre-infusion risk evaluation model, cytokine release syndrome-pre-infusion risk evaluation (CRS-PRE), that stratified grade ≥ 2 CRS risk into low, intermediate and high groups with incidences of 2.8%, 26.0% and 50.0% respectively. Decreased eGFR, a surrogate of host renal reserve, with elevated ferritin, CRP and LDH emerged as predictors of high-grade CRS. The CRS-PRE may facilitate risk-adapted monitoring and intervention in clinical practice. en-copyright= kn-copyright= en-aut-name=AraiYasuyuki en-aut-sei=Arai en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=JoTomoyasu en-aut-sei=Jo en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoTakayuki en-aut-sei=Sato en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakuraiMasatoshi en-aut-sei=Sakurai en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KajiDaisuke en-aut-sei=Kaji en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitawakiToshio en-aut-sei=Kitawaki en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimadaKazuyuki en-aut-sei=Shimada en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimoyamaTatsu en-aut-sei=Shimoyama en-aut-mei=Tatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshiharaSatoshi en-aut-sei=Yoshihara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MakitaShinichi en-aut-sei=Makita en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamamotoGo en-aut-sei=Yamamoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KataokaKeisuke en-aut-sei=Kataoka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SakaidaEmiko en-aut-sei=Sakaida en-aut-mei=Emiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=GotoHideki en-aut-sei=Goto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NakashimaYasuhiro en-aut-sei=Nakashima en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YoshidaAkiyo en-aut-sei=Yoshida en-aut-mei=Akiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UmezawaYoshihiro en-aut-sei=Umezawa en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KimHaryoon en-aut-sei=Kim en-aut-mei=Haryoon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KatoMotohiro en-aut-sei=Kato en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=2 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=5 en-affil=Department of Hematology, Toranomon Hospital kn-affil= affil-num=6 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Nagoya University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Division of Clinical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=9 en-affil=Department of Hematology, Hyogo Medical University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, National Cancer Center Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology, Toranomon Hospital kn-affil= affil-num=13 en-affil=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=14 en-affil=Department of Hematology, Chiba University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology, Hokkaido University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology, Osaka Metropolitan University Hospital kn-affil= affil-num=17 en-affil=Department of Hematology, Kanazawa University Hospital kn-affil= affil-num=18 en-affil=Department of Hematology, Institute of Science Tokyo Hospital kn-affil= affil-num=19 en-affil=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=20 en-affil=Department of Pediatrics, The University of Tokyo kn-affil= affil-num=21 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=22 en-affil=Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital kn-affil= en-keyword=chimeric antigen receptor T-cell therapy kn-keyword=chimeric antigen receptor T-cell therapy en-keyword=cytokine release syndrome kn-keyword=cytokine release syndrome en-keyword=estimated glomerular filtration rate kn-keyword=estimated glomerular filtration rate en-keyword=large B-cell lymphoma kn-keyword=large B-cell lymphoma END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue= article-no= start-page=148 end-page=159 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Behavioral effects of a chronic envy-like stress paradigm in mice using an adjacent cage model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Social comparison and envy are significant psychosocial stressors in humans and are known to be involved in the onset and persistence of psychiatric disorders. However, animal models capable of experimentally reproducing the effects of indirect social comparison without physical contact are limited. In this study, we used a newly developed "adjacent-cage paradigm" to investigate whether chronic vicarious exposure to conspecifics in different environments induces envy-like stress in mice.
Methods: Male C57BL/6 N mice served as observers, while demonstrator mice were assigned to one of four conditions: (1) an environment enriched with objects, (2) an igloo, (3) a tube, or (4) social isolation. Observers were continuously exposed to these adjacent cages for 21 days. Subsequently, a comprehensive battery of behavioral tests was conducted to assess general health, anxiety-like behavior, spatial memory, social behavior, and depression-like behavior.
Results: In the objects condition, a decrease in time spent in the light compartment of the light/dark box indicated an increase in anxiety-like behavior. In the isolation condition, the mean duration per social interaction was shortened, suggesting a qualitative change in social behavior. The igloo condition resulted in reduced immobility time in the forced swim test, suggesting a possible alteration in stress coping behavior. Furthermore, increased nociceptive sensitivity was observed in the hot plate test under both the objects and isolation conditions.
Conclusion: Although the envy-like stress paradigm did not affect many behavioral indices, it did cause condition-dependent and limited behavioral changes. This suggests that the paradigm may serve as a novel model for capturing psychological and context-dependent social stress, which differs from conventional physical stress models. Elucidating the neural basis of this paradigm is expected to contribute to the understanding of how social comparison affects mental health in modern society. en-copyright= kn-copyright= en-aut-name=UenoHiroshi en-aut-sei=Ueno en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaYoshihiro en-aut-sei=Tanaka en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitanoEriko en-aut-sei=Kitano en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriSachiko en-aut-sei=Mori en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MurakamiShinji en-aut-sei=Murakami en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WaniKenta en-aut-sei=Wani en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkamotoMotoi en-aut-sei=Okamoto en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=2 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=8 en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= en-keyword=envy-like stress kn-keyword=envy-like stress en-keyword=social comparison kn-keyword=social comparison en-keyword=psychosocial stress kn-keyword=psychosocial stress en-keyword=mouse model kn-keyword=mouse model en-keyword=anxiety-like behavior kn-keyword=anxiety-like behavior END start-ver=1.4 cd-journal=joma no-vol=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=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=27 cd-vols= no-issue=6 article-no= start-page=2645 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260313 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Minimal Association Between Immunoglobulin A Coating and Gut Microbiota Alterations Induced by High-Fat Diets with Distinct Fatty Acid Compositions en-subtitle= kn-subtitle= en-abstract= kn-abstract=High-fat diets (HFDs) containing dietary fats with different fatty acid (FA) compositions alter gut microbiota composition in a fat-source-dependent manner. Immunoglobulin A (IgA) and unabsorbed lipids in the distal gut are potential regulators of the gut microbiota. However, their roles in mediating gut microbiota alterations induced by dietary fats with different FA compositions remain unclear. This study aims to examine the associations of these two factors with fat-source-dependent gut microbiota alterations. BALB/c mice were fed a normal diet, a high-lard diet, a high-olive oil diet, or a high-soybean oil diet for 27 weeks. Fecal samples were collected to assess microbiota composition, the IgA coating index (ICI)—which quantifies the extent of IgA coating on gut microbiota—and fecal fatty acid concentrations. At the phylum level, the concentration of fecal total long-chain fatty acids (LCFAs) was positively correlated with the relative abundance (RA) of Bacillota and negatively correlated with that of Bacteroidota. In addition, a trend toward a positive association between the RA and the ICI was observed for Bacillota but not for Bacteroidota. At the genus level, the RAs of 12 taxa were positively correlated with fecal LCFA concentrations, whereas those of 6 taxa were negatively correlated. Although the RAs of most taxa appeared to be influenced by unabsorbed lipids and additional factors, only four Bacillota genera exhibited a positive correlation between the RA and the ICI. Our observations suggest that IgA coating of the gut microbiota may have a minimal association with fat-source-specific alterations in gut microbiota composition during HFD intake. en-copyright= kn-copyright= en-aut-name=TeraokaMao en-aut-sei=Teraoka en-aut-mei=Mao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishinoNaoki en-aut-sei=Nishino en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangTianyang en-aut-sei=Wang en-aut-mei=Tianyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChenKuiyi en-aut-sei=Chen en-aut-mei=Kuiyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsurutaTakeshi en-aut-sei=Tsuruta en-aut-mei=Takeshi 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= Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil= Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil= Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=immunoglobulin A kn-keyword=immunoglobulin A en-keyword=high-fat diet kn-keyword=high-fat diet en-keyword=gut microbiota kn-keyword=gut microbiota en-keyword=fatty acid composition kn-keyword=fatty acid composition END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue=6 article-no= start-page=1319 end-page=1328 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260326 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Institutional Variability in Brain-Dead Organ Donation Processes and Practices: A Multicenter Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=OBJECTIVES: To determine whether key institutional and clinical differences exist between highly and moderately active hospitals in Japan with respect to brain-dead organ donation practices.
DESIGN: Retrospective multicenter cohort study.
SETTING: Sixteen tertiary emergency and critical care centers across Japan.
PATIENTS: All brain-dead organ donors from participating institutions who had at least one organ procured and transplanted between July 17, 2010, and December 31, 2023. Hospitals were categorized as highly active (≥ 14 donations) or moderately active (≤ 13 donations) during the study period.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Institutional donation practices were compared, including donor management strategies, use of vasopressors and corticosteroids, time intervals in the donation process, and frequency of multidisciplinary team meetings. A total of 204 donors were included; the median age was 47 years (interquartile range, 37–56), and 92 (45.1%) were female. Donor characteristics were similar between groups. Vasopressin was used in nearly all donors, though dosing protocols varied. Corticosteroid use was significantly higher in highly active hospitals compared with moderately active ones (58.3% vs. 38.0%; p = 0.004). Time from admission to coordinator notification was similar; however, time to family consent (median, 8 vs. 5 d; p < 0.001) and time to organ procurement (median, 12 vs. 9 d; p = 0.006) were longer in highly active hospitals. These hospitals also conducted more multidisciplinary meetings during donor management (median, 2 vs. 0; p < 0.001).
CONCLUSIONS: Highly active hospitals demonstrated more intensive donor management practices, longer timeframes for key donation steps, and greater multidisciplinary engagement. Standardization of donation practices may enhance efficiency and support broader dissemination of effective institutional strategies to improve brain-dead organ donation rates in Japan. 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=Japan Comprehensive Process for End-of-Life Care and Organ Donation after Brain Death (J-RESPECT) study group en-aut-sei=Japan Comprehensive Process for End-of-Life Care and Organ Donation after Brain Death (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 and Critical Care Medicine, Nippon Medical School 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 and Critical Care Medicine, Nippon Medical School 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=critical illness kn-keyword=critical illness en-keyword=decision-making kn-keyword=decision-making en-keyword=organ transplantation kn-keyword=organ transplantation en-keyword=patient care kn-keyword=patient care 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=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=18 cd-vols= no-issue=3 article-no= start-page=e105091 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Septic Arthritis of the Temporomandibular Joint Complicated by Dislocation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Septic arthritis of the temporomandibular joint (SATMJ) is a rare but potentially serious condition, and standardized diagnostic and therapeutic strategies have not been established. We present the case of a 70-year-old man who developed acute right temporomandibular joint (TMJ) pain, swelling, mandibular deviation, and inability to achieve mouth closure. Computed tomography and magnetic resonance imaging revealed right TMJ dislocation, joint effusion, degenerative changes, and anterior disc displacement with effusion. Aspiration of the joint yielded neutrophil-predominant purulent fluid, although bacterial cultures were negative. The patient was treated empirically with intravenous ceftriaxone followed by oral clindamycin and amoxicillin, resulting in rapid symptom resolution, and the dislocation spontaneously reduced without surgical intervention. No recurrence was observed during three months of follow-up. This case highlights the diagnostic challenges associated with culture-negative SATMJ, supports the role of early empirical antibiotic therapy, and suggests that chronic joint instability due to habitual dislocation may predispose the TMJ to infection. en-copyright= kn-copyright= en-aut-name=KanemotoHideka en-aut-sei=Kanemoto en-aut-mei=Hideka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UmemoriKoki en-aut-sei=Umemori en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Oral Surgery, Kochi Health Sciences Center kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine kn-affil= en-keyword=antibiotics kn-keyword=antibiotics en-keyword=culture-negative infection kn-keyword=culture-negative infection en-keyword=joint dislocation kn-keyword=joint dislocation en-keyword=septic arthritis kn-keyword=septic arthritis en-keyword=temporomandibular joint kn-keyword=temporomandibular joint END start-ver=1.4 cd-journal=joma no-vol=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=75 cd-vols= no-issue=4 article-no= start-page=121 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immunological effects of amivantamab in EGFR or MET-expressing non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Epidermal growth factor receptor (EGFR) mutations represent one of the most frequent oncogenic driver in non-small cell lung cancer (NSCLC). Amivantamab, a bispecific antibody targeting EGFR and MET proto-oncogene, receptor tyrosine kinase (MET), has demonstrated clinical benefit in EGFR-mutant NSCLC through dual blockade, but its immunological role in human clinical specimens, especially tumor-infiltrating lymphocytes (TILs), has not been directly evaluated.
Methods We analyzed surgically resected tumor samples from 40 patients with NSCLC to investigate immune responses and their associations with EGFR and MET expression. TILs were characterized by flow cytometry (FCM) and immunohistochemistry (IHC). To assess the immunomodulatory potential of amivantamab, fresh tumor digests containing live tumor cells and TILs were cultured ex vivo with CD3 and CD28 stimulation in the absence or presence of amivantamab, followed by FCM. EGFR and MET expression were also evaluated by IHC.
Results EGFR mutations and high EGFR protein expression were associated with a trend toward reduced CD8⁺ T-cell and dendritic cell (DC) infiltration. In ex vivo TIL assays, exposure to amivantamab significantly activated CD8⁺ T cells, such as programmed cell death-1 expression and cytokine production, and promoted DC maturation. These effects were most pronounced in tumors with high EGFR or MET protein expression rather than EGFR mutations.
Conclusions This study provides the first direct evidence from ex vivo fresh TIL assays using human NSCLC clinical specimens that amivantamab can activate immune responses. EGFR and MET expression may serve as potential biomarkers for amivantamab-induced immune responses. en-copyright= kn-copyright= en-aut-name=YoshichikaRyo en-aut-sei=Yoshichika en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MukoharaFumiaki en-aut-sei=Mukohara en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaKotaro en-aut-sei=Yamada en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=WatanabeHiroko en-aut-sei=Watanabe en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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 Respiratory Medicine, Okayama University Hospital 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 Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University kn-affil= affil-num=10 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer en-keyword=Amivantamab kn-keyword=Amivantamab en-keyword=Antitumor immunity kn-keyword=Antitumor immunity en-keyword=EGFR kn-keyword=EGFR en-keyword=MET kn-keyword=MET END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=3 article-no= start-page=100926 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Potential Immune Microenvironment Biomarkers in SCLC: J-TAIL-2 Observational Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Effective predictors of response to atezolizumab plus carboplatin/etoposide (CE) therapy in extensive-stage SCLC (ES-SCLC) remain limited. This exploratory analysis from J-TAIL-2 aimed to identify markers of survival benefit with atezolizumab plus CE therapy in ES-SCLC.
Methods: J-TAIL-2 (ClinicalTrials.gov ID, NCT04501497) was a multicenter observational study that enrolled patients receiving atezolizumab plus CE (ES-SCLC cohort) in clinical practice in Japan per local label and treatment guidelines. In this exploratory analysis, the association of CD8+ tumor-infiltrating lymphocyte (TIL) density and SCLC subtypes (SCLC-A [ASCL1 dominant], SCLC-N [NEUROD1 dominant], SCLC-P [ASCL1/NEUROD1 double-negative with POU2F3 expression], and SCLC-O [ASCL1/NEUROD1 double-negative not otherwise specified]) with overall survival (OS) and progression-free survival (PFS) was evaluated. SCLC subtyping was performed by immunohistochemistry.
Results: SCLC samples (n = 100; data cutoff, February 3, 2023) were categorized as SCLC-A (73%), SCLC-N (16%), SCLC-P (8%), and SCLC-O (3%). Among 96 patients who received first-line atezolizumab plus CE, median age was 72 (range, 39–87) years and 81% were male. Furthermore, 56 patients were classified into the CD8+ TIL-high subgroup and 40 into the TIL-low subgroup. Median (m)PFS with atezolizumab plus CE was 6.1 months (95% confidence interval [CI]: 4.5–7.5) in the TIL-high versus 4.4 months (95% CI: 4.0–5.1) in the TIL-low subgroup (p = 0.01); mOS was 18.4 (95% CI: 11.8–not estimable) versus 10.8 months (95% CI: 7.7–16.2; p = 0.04). mOS and mPFS were not significantly different between SCLC subtypes but were numerically shorter in the SCLC-N group.
Conclusions: CD8+ TIL density is a potential biomarker of clinical benefit in ES-SCLC and may facilitate patient selection for atezolizumab combination therapy. en-copyright= kn-copyright= en-aut-name=ShirasawaMasayuki en-aut-sei=Shirasawa en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishioMakoto en-aut-sei=Nishio en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OsoegawaAtsushi en-aut-sei=Osoegawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuchiEiki en-aut-sei=Kikuchi en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KimuraHideharu en-aut-sei=Kimura en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GotoYasushi en-aut-sei=Goto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuJunichi en-aut-sei=Shimizu en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyauchiEisaku en-aut-sei=Miyauchi en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshinoIchiro en-aut-sei=Yoshino en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MisumiToshihiro en-aut-sei=Misumi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YatabeYasushi en-aut-sei=Yatabe en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YoshidaTatsuya en-aut-sei=Yoshida en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KashimaJumpei en-aut-sei=Kashima en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OkiMasahide en-aut-sei=Oki en-aut-mei=Masahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AshimuraHisao en-aut-sei=Ashimura en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KobayashiYuki en-aut-sei=Kobayashi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TanakaMisa en-aut-sei=Tanaka en-aut-mei=Misa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=GemmaAkihiko en-aut-sei=Gemma en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Kanazawa University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Thoracic Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Tohoku University Hospital kn-affil= affil-num=10 en-affil=Department of Thoracic Oncology, Kansai Medical University kn-affil= affil-num=11 en-affil=International University of Health and Welfare Narita Hospital kn-affil= affil-num=12 en-affil=Department of Data Science, National Cancer Center Hospital East kn-affil= affil-num=13 en-affil=Department of Diagnostic Pathology, National Cancer Center Hospital kn-affil= affil-num=14 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=15 en-affil=Department of Diagnostic Pathology, National Cancer Center Hospital kn-affil= affil-num=16 en-affil=Department of Respiratory Medicine, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=18 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=19 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=20 en-affil=Nippon Medical School kn-affil= en-keyword=Small cell kn-keyword=Small cell en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Atezolizumab kn-keyword=Atezolizumab en-keyword=Chemotherapy kn-keyword=Chemotherapy en-keyword=Immune microenvironment kn-keyword=Immune microenvironment END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=139 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260409 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pseudoaneurysm of the thoracoacromial artery associated with habitual shoulder dislocation: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Shoulder dislocation is one of the most common joint dislocations encountered in emergency departments, but vascular complications are rare and often underrecognized. Pseudoaneurysms of the thoracoacromial artery, a branch of the axillary artery, are extremely uncommon and may present with subtle symptoms, delaying diagnosis.
Case presentation An 82-year-old woman with a history of habitual anterior shoulder dislocation presented with a 10-day history of progressive pain and swelling in the left shoulder. She was on edoxaban for atrial fibrillation. Examination revealed localized tenderness and swelling without neurological deficits. Computed tomography angiography showed a 30 × 35 × 35 mm pseudoaneurysm arising from the acromial branch of the thoracoacromial artery. Endovascular embolization was performed using a proximal oxidized regenerated cellulose sheet placement followed by injection of N-butyl cyanoacrylate and Lipiodol due to the risk of coil migration into the joint space. The procedure achieved complete exclusion of the lesion. At three-month follow-up, the patient remained asymptomatic with preserved left upper limb function. Computed tomography angiography demonstrated the pseudoaneurysm remains excluded.
Conclusion Although rare, pseudoaneurysms of the thoracoacromial artery can occur after repeated shoulder dislocation and reduction, especially in elderly patients on anticoagulation therapy. Early recognition through imaging and prompt endovascular intervention can prevent serious vascular and neurological complications. en-copyright= kn-copyright= en-aut-name=WadaHonoka en-aut-sei=Wada en-aut-mei=Honoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamasakiAya en-aut-sei=Hamasaki en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkamotoSoichiro en-aut-sei=Okamoto en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoShunki en-aut-sei=Yamamoto en-aut-mei=Shunki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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 Radiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Pseudoaneurysm kn-keyword=Pseudoaneurysm en-keyword=Thoracoacromial artery kn-keyword=Thoracoacromial artery en-keyword=Shoulder dislocation kn-keyword=Shoulder dislocation en-keyword=Anticoagulation kn-keyword=Anticoagulation en-keyword=Endovascular embolization kn-keyword=Endovascular embolization 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=21 cd-vols= no-issue=3 article-no= start-page=e0339600 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Early administration of renin–angiotensin system inhibitors improves survival and cardiac remodeling in heart failure with preserved ejection fraction en-subtitle= kn-subtitle= en-abstract= kn-abstract=Heart failure with preserved ejection fraction (HFpEF) is a major cardiovascular disease that accounts for 50% of all cases of heart failure. Patients with HFpEF have limited therapeutic options because of the complex pathogenesis of this disease. Decreased nitric oxide (NO) levels and increased renin–angiotensin system (RAS) activity may be associated with HFpEF pathogenesis. However, whether soluble guanylate cyclase (sGC) stimulators and RAS inhibitors protect against HFpEF remains unclear. This study aimed to evaluate the preventive effects of RAS inhibitors captopril (Cap) and/or sacubitril/valsartan (Sac/Val) and sGC stimulator vericiguat (Ver) on HFpEF progression. HFpEF was induced in 8-week-old male Wistar rats through intake of L-arginine methyl ester and a high-fat diet. Results showed that the survival rate after 8 weeks of treatment was 100% in the normal diet (Cont group), Cap, and Sac/Val groups, whereas it was approximately 20% in the HFpEF and Ver groups. No significant differences in the left ventricular systolic function were found. In addition, histochemistry revealed that myocardial hypertrophy and interstitial fibrosis obviously increased in the HFpEF group but not in the Cap and Sac/Val groups compared with the Cont group. Furthermore, RNA sequencing analysis showed that the expression of genes related to inflammatory response, hypertrophy, and extracellular matrix–receptor interaction increased in the HFpEF group and decreased in the Cap and Sac/Val groups. In conclusion, early administration of Cap or Sac/Val may reduce the risk of developing HFpEF by inhibiting the RAS pathway rather than the NO-sGC-cGMP pathway. en-copyright= kn-copyright= en-aut-name=KonoYuka en-aut-sei=Kono en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SonodaKunihiro en-aut-sei=Sonoda en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhtakeKazuo en-aut-sei=Ohtake en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtaAkinobu en-aut-sei=Ota en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoShusei en-aut-sei=Yamamoto en-aut-mei=Shusei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakayamaHinako en-aut-sei=Nakayama en-aut-mei=Hinako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FukuokaTaketo en-aut-sei=Fukuoka en-aut-mei=Taketo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaiYuki en-aut-sei=Kawai en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TagoHaruka en-aut-sei=Tago en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeNobuhisa en-aut-sei=Watanabe en-aut-mei=Nobuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SatoIkumi en-aut-sei=Sato en-aut-mei=Ikumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HirohataSatoshi en-aut-sei=Hirohata en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KitamoriKazuya en-aut-sei=Kitamori en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=WatanabeShogo en-aut-sei=Watanabe en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Collage of Human Life and Environment, Kinjo Gakuin University kn-affil= affil-num=3 en-affil=School of Pharmacy, Faculty of Pharmaceutical Science, Josai University kn-affil= affil-num=4 en-affil=Collage of Human Life and Environment, Kinjo Gakuin University kn-affil= affil-num=5 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=11 en-affil=Academic Field of Health Science, Okayama University kn-affil= affil-num=12 en-affil=Academic Field of Health Science, Okayama University kn-affil= affil-num=13 en-affil=Collage of Human Life and Environment, Kinjo Gakuin University kn-affil= affil-num=14 en-affil=Academic Field of Health Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue= article-no= start-page=1759690 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260309 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of a generative AI agent for family support in implementing family-based treatment for children and adolescents with anorexia nervosa en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Family-based treatment (FBT) is a first-line psychotherapy for children and adolescents with anorexia nervosa (AN). However, families must understand the principles of FBT, provide meal support, and manage their children's pathological behaviors. Difficulties occur outside clinic hours when it is impossible to consult professionals. This “support gap” increases caregivers’ psychological distress and threatens their treatment continuity. To the best of our knowledge, this is the first domain-specific generative artificial intelligence (AI) agent designed to provide situation-specific, FBT-concordant advice and psychological support.
Methods: The system integrates three components: (1) an FBT-specific knowledge base constructed from treatment manuals, family guides, guideline-compliant resources, and a clinical Q&A corpus; (2) a multistage natural language processing pipeline using Retrieval-Augmented Generation (RAG), with intent and sentiment analyses; and (3) safety guardrails that prohibit unsolicited numerical goals or direct hospitalization recommendations and standardized escalation to clinicians. When strong negative emotions are detected, empowerment messages are dynamically incorporated to maintain caregivers’ confidence. Six clinicians with expertise with pediatric mental health authored queries that simulated common FBT-related concerns and evaluated each response for clinical appropriateness and safety, and classified problems as information insufficiency, not FBT concordant, or escalation insufficiency.
Results: Of the 477 queries, 57.0% were FBT-related, 24.5% were general AN, 16.5% were parental psychological distress, and 1.8% were related to other topics. The clinically appropriate response rate was 91.6% (437/477), including 92.3% for FBT-related questions, 88.0% for general knowledge, 93.7% for psychological distress, and 100.0% for other questions. Clinically inappropriate responses (8.4%) were mainly attributable to information insufficiency; not FBT concordant (1.8% of FBT-related responses) and escalation insufficiency (0.6% of all dialogs) rarely occurred.
Discussion: In this expert review, the safety-gated RAG system predominantly generated FBT-concordant responses that provided meal-level guidance and empathic empowerment-oriented support to families. By proceduralizing complex FBT concepts and presenting multiple response options for pathological behaviors, the system translates FBT principles into practical guidance supporting refeeding adherence, preserving family self-efficacy, and suggesting that domain-specific AI may help bridge structural limitations in FBT. Usability studies and randomized controlled trials are warranted to determine their impact on caregiver burden, self-efficacy, treatment adherence, and clinical outcomes. en-copyright= kn-copyright= en-aut-name=HanzawaMana en-aut-sei=Hanzawa en-aut-mei=Mana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkadaAyumi en-aut-sei=Okada en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaChie en-aut-sei=Tanaka en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShigeyasuYoshie en-aut-sei=Shigeyasu en-aut-mei=Yoshie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiiChikako en-aut-sei=Fujii en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HoriuchiMakiko en-aut-sei=Horiuchi en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiharaAkiko en-aut-sei=Sugihara en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakeuchiKoichi en-aut-sei=Takeuchi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakaharaRyuichi en-aut-sei=Nakahara en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatayamaHideki en-aut-sei=Katayama en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakahashiYasushi en-aut-sei=Takahashi en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Hospital Medical Center for Children kn-affil= affil-num=2 en-affil=Department of Medical Informatics and Clinical Support Technology Development, Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital Medical Center for Children kn-affil= affil-num=4 en-affil=Department of Pediatrics, Okayama University Hospital Medical Center for Children kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama University Hospital Medical Center for Children kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Hospital Medical Center for Children kn-affil= affil-num=7 en-affil=Clinical Psychology Section, Department of Medical Support, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pediatrics, Okayama University Hospital Medical Center for Children kn-affil= affil-num=9 en-affil=Life Natural Science and Technology, Graduate School of Environmental, Okayama University kn-affil= affil-num=10 en-affil=Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Palliative and Supportive Care, Okayama University Hospital kn-affil= affil-num=12 en-affil=NEC Corporation kn-affil= affil-num=13 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Pediatrics, Okayama University Hospital Medical Center for Children kn-affil= en-keyword=anorexia nervosa kn-keyword=anorexia nervosa en-keyword=caregiver burden kn-keyword=caregiver burden en-keyword=family support kn-keyword=family support en-keyword=family-based treatment kn-keyword=family-based treatment en-keyword=generative AI agent kn-keyword=generative AI agent en-keyword=large language model kn-keyword=large language model en-keyword=retrieval-augmented generation kn-keyword=retrieval-augmented generation END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=2 article-no= start-page=100082 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=Pharmaceutical agents targeting KATP channel modulate sweet taste sensitivity in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sweet detection involves at least two mechanisms: a G-protein coupled sweet taste receptor (Tas1r2/Tas1r3) and glucose transporters. As in pancreatic β-cells, glucose transport may lead to closure of ATP-sensitive potassium (KATP) channels. Since expression of KATP channels in sweet taste cells has been reported, modulation of KATP channel activity would affect sweet taste sensitivity. Here, we examined the effect of glibenclamide (a KATP channel closer) and diazoxide (an opener) on mouse taste behavior. Glibenclamide selectively reduced taste sensitivity to glucose without affecting responses to sucrose or sucralose compared to insulin, suggesting selective impairment of the transporter-dependent pathway. In contrast, diazoxide broadly suppressed responses to all tested sweeteners, indicating a generalized effect on sweet detection. Neither drug altered responses to non-sweet taste. These findings suggest that pharmacological modulation of KATP channel differently influences sweet taste; closers reduce glucose sensitivity whereas openers attenuate response to multiple sweeteners. en-copyright= kn-copyright= en-aut-name=SawaiChika en-aut-sei=Sawai en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangKuanyu en-aut-sei=Wang en-aut-mei=Kuanyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= en-aut-name=UedaHirotaka en-aut-sei=Ueda en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= affil-num=1 en-affil=Department of Orthodontics, 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 Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Sweet taste receptor kn-keyword=Sweet taste receptor en-keyword=Glucose transporter kn-keyword=Glucose transporter en-keyword=Diabetes kn-keyword=Diabetes en-keyword=Taste disorder kn-keyword=Taste disorder en-keyword=Cephalic phase insulin release kn-keyword=Cephalic phase insulin release 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=223 cd-vols= no-issue= article-no= start-page=108646 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=Reticulate evolution, introgression, and recent diversification in Epimedium sect. Macroceras en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hybridization can hinder or promote diversification, and growing genomic evidence suggests that it can facilitate adaptation and speciation. Despite recent progress, however, the quantitative contribution and temporal scope of hybridization to diversification remain poorly understood. The genus Epimedium is a recently diverged lineage, and sect. Macroceras largely consists of endemic species in Japan that are distributed across diverse environments, including limestone, serpentine, coastal habitats, heavy-snow regions, and regions with mild winters. Although natural hybridization and hybrid species have been reported in this section, molecular evidence demonstrating the contribution of hybridization to lineage diversification is limited. We reconstructed phylogenetic relationships using genome-wide single-nucleotide polymorphism (SNP) data from Epimedium sect. Macroceras and tested for genomic signatures consistent with hybridization. Phylogenetic analyses suggest that E. koreanum from Korea is sister to Japanese Epimedium lineages, consistent with an initial colonization of Japan from the Korean Peninsula. The analyses also revealed complex relationships among Japanese species and frequent signals of historical interspecific introgression. Our results are consistent with a history of recent diversification in sect. Macroceras accompanied by introgressive hybridization, which may have contributed to diversification across heterogeneous environments in Japan. This study provides the first genome-wide insights into the evolutionary history of Epimedium sect. Macroceras and reveals complex reticulate relationships among the lineages. en-copyright= kn-copyright= en-aut-name=KusatakeEmi en-aut-sei=Kusatake en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KonishiMomoka en-aut-sei=Konishi en-aut-mei=Momoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomokuniShuto en-aut-sei=Tomokuni en-aut-mei=Shuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YanagiYosuke en-aut-sei=Yanagi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KariyamaShungo en-aut-sei=Kariyama en-aut-mei=Shungo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItohTakehito en-aut-sei=Itoh en-aut-mei=Takehito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyodaAtsushi en-aut-sei=Toyoda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KimSeung-Chul en-aut-sei=Kim en-aut-mei=Seung-Chul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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= affil-num=4 en-affil=Department of Biology, Okayama University kn-affil= affil-num=5 en-affil=Society of Kurashiki Museum of Natural History kn-affil= affil-num=6 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=7 en-affil=Department of Genomics and Evolutionary Biology, National Institute of Genetics kn-affil= affil-num=8 en-affil=Department of Biological Sciences, Sungkyunkwan University kn-affil= affil-num=9 en-affil=Department of Biology, Okayama University kn-affil= en-keyword=Phylogenomics kn-keyword=Phylogenomics en-keyword=Introgression kn-keyword=Introgression en-keyword=Evolutionary radiation kn-keyword=Evolutionary radiation en-keyword=Pleistocene kn-keyword=Pleistocene en-keyword=Ecological divergence kn-keyword=Ecological divergence en-keyword=Reticulate evolution kn-keyword=Reticulate evolution END start-ver=1.4 cd-journal=joma no-vol=105 cd-vols= no-issue=5 article-no= start-page=255 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260420 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=HLA-matched versus haploidentical donor transplantation with post-transplant cyclophosphamide: a study on behalf of the donor/source working group of the Japanese society for transplantation and cellular therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Post-transplant cyclophosphamide (PTCy) is now being increasingly applied to HLA-matched donor (MD) transplantation. Prior studies in Western countries have demonstrated that allogeneic hematopoietic cell transplantation (allo-HCT) employing PTCy yields better outcomes with HLA-matched donors (MDs) than with haploidentical donors (HIDs). However, the effect of HLA mismatch may differ among racial groups. We retrospectively analyzed adult patients with hematological malignancies who underwent their first allo-HCT with PTCy from MDs or HIDs registered to the Japanese registry database between 2013 and 2021. Among 63 (related, n = 33; unrelated, n = 30) and 1261 patients who received MD and HID allo-HCT with PTCy, 50 (related, n = 30; unrelated, n = 20) and 100 patients were assigned to MD and HID groups by 1:2 propensity score matching (PSM). The results showed that MD recipients had better neutrophil recovery (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.04–2.10; P = 0.031) and lower risk of non-relapse mortality (NRM) (HR, 0.19; 95% CI, 0.05–0.81; P = 0.024) than HID recipients. Multivariable analyses in the entire cohort before PSM confirmed these findings. Fatal infection was the primary cause of NRM in the HID group. This study is the first to demonstrate that, within a homogeneous Asian cohort, MD may have an advantage over HID in PTCy-based allo-HCT in facilitating neutrophil engraftment and reducing the risk of NRM. en-copyright= kn-copyright= en-aut-name=NakayaYosuke en-aut-sei=Nakaya en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamaeHirohisa en-aut-sei=Nakamae en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugitaJunichi en-aut-sei=Sugita en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=HasegawaYuta en-aut-sei=Hasegawa en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EtoTetsuya en-aut-sei=Eto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FukudaTakahiro en-aut-sei=Fukuda en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KuritaNaoki en-aut-sei=Kurita en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiramotoNobuhiro en-aut-sei=Hiramoto en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NagafujiKoji en-aut-sei=Nagafuji en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OtaShuichi en-aut-sei=Ota en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AndoToshihiko en-aut-sei=Ando en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawakitaToshiro en-aut-sei=Kawakita en-aut-mei=Toshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AkasakaTakashi en-aut-sei=Akasaka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MoriYasuo en-aut-sei=Mori en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KamimuraTomohiko en-aut-sei=Kamimura en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OnizukaMakoto en-aut-sei=Onizuka en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 ORCID= en-aut-name=NakasoneHideki en-aut-sei=Nakasone en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Hematology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Hematology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Hematology, Sapporo Hokuyu Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=5 en-affil=Department of Hematology, Hokkaido University Hospital kn-affil= affil-num=6 en-affil=Department of Hematology, Hamanomachi Hospital kn-affil= affil-num=7 en-affil=Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, University of Tsukuba Hospital kn-affil= affil-num=9 en-affil=Department of Hematology, Kobe City Medical Center General Hospital kn-affil= affil-num=10 en-affil=Division of Hematology and Oncology, Department of Medicine, Kurume University HospitalDepartment of Hematology, Sapporo Hokuyu Hospital kn-affil= affil-num=11 en-affil=Department of Hematology, Sapporo Hokuyu Hospital kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University kn-affil= affil-num=14 en-affil=Department of Hematology, NHO Kumamoto Medical Center kn-affil= affil-num=15 en-affil=Department of Hematology, Tenri Hospital kn-affil= affil-num=16 en-affil=Hematology, Oncology & Cardiovascular medicine, Kyushu University Hospital kn-affil= affil-num=17 en-affil=Department of Hematology, Harasanshin Hospital kn-affil= affil-num=18 en-affil=Department of Hematology/Oncology, Tokai University School of Medicine kn-affil= affil-num=19 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=20 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Center kn-affil= en-keyword=Post-transplant cyclophosphamide kn-keyword=Post-transplant cyclophosphamide en-keyword=Matched donor kn-keyword=Matched donor en-keyword=Haploidentical donor kn-keyword=Haploidentical donor en-keyword=Graft-versus-host disease kn-keyword=Graft-versus-host disease en-keyword=Hematological malignancies. kn-keyword=Hematological malignancies. END start-ver=1.4 cd-journal=joma no-vol=2026 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Peripheral Odontogenic Myxofibroma Arising in the Palatal Gingiva of the Maxillary Second Premolar Region: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Odontogenic myxofibroma (OMF) is a rare benign mesenchymal odontogenic tumor characterized by myxoid stroma with a prominent fibrous component. Although it usually arises intraosseously within the jaws, the peripheral variant, peripheral odontogenic myxofibroma (POMF), which occurs in extraosseous soft tissues, is uncommon and may be clinically misdiagnosed as a reactive gingival lesion. We report a case of POMF in a 68-year-old man who was referred for evaluation of a painless, slowly enlarging swelling of the palatal gingiva in the left maxillary second premolar region, which had initially been diagnosed as chronic periodontitis at a local clinic. An intraoral examination revealed an elastic, firm mass with partial erythema on the palatal marginal gingiva. Panoramic radiography showed mild generalized horizontal bone loss without lesion-specific changes, and computed tomography revealed no bone resorption associated with the lesion. Exfoliative cytology was negative for intraepithelial lesions or malignancy. The lesion was excised with a 5-mm clinical margin, including periosteum, and superficial peripheral ostectomy of the adjacent cortical bone was performed. Histopathological examination revealed a myxoid stroma rich in mucinous matrix and collagen fibers, containing sparsely distributed spindle-shaped cells and scattered nests of odontogenic epithelium. Alcian blue staining revealed diffuse positivity, supporting the diagnosis of POMF. No recurrence was observed during a 2-year follow-up period. This case highlights a diagnostic pitfall in the tooth-bearing gingiva and underscores the importance of histopathological confirmation of persistent gingival masses. When imaging shows no apparent bone involvement, and clinical suspicion of malignancy is low, complete excision with an adequate soft-tissue margin and selective, limited bone removal may achieve local control while preserving the adjacent teeth; long-term follow-up remains advisable. en-copyright= kn-copyright= en-aut-name=MasuiMasanori en-aut-sei=Masui en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YutoriHirokazu en-aut-sei=Yutori en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujimuraAi en-aut-sei=Fujimura en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery , Faculty of Medicine , Dentistry and Pharmaceutical Sciences Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery , Kagawa Prefectural Central Hospital kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery , Kagawa Prefectural Central Hospital kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery , Faculty of Medicine , Dentistry and Pharmaceutical Sciences Okayama University kn-affil= en-keyword=case report kn-keyword=case report en-keyword=excisional biopsy kn-keyword=excisional biopsy en-keyword=palatal gingiva kn-keyword=palatal gingiva en-keyword=peripheral odontogenic myxofibroma kn-keyword=peripheral odontogenic myxofibroma en-keyword=peripheral odontogenic myxoma kn-keyword=peripheral odontogenic myxoma 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=Effects of Juniperus sabina coverage on plant community structure in semiarid areas of China en-subtitle= kn-subtitle= en-abstract= kn-abstract=Plant interactions are one of the fundamental processes shaping the structure and function of plant communities and help create species diversity. Species diversity affects the current functioning of ecosystems and their resistance and resilience to future climate change. In harsh environments such as drylands, positive plant–plant interactions are important in promoting species diversity. Juniperus sabina is an evergreen shrub that is native to the semiarid areas of northern China. Because J. sabina can modify some harsh environmental conditions in its role as a nurse plant, it is expected to facilitate species diversity, although it may exhibit allelopathic inhibition. Previous research has only examined effects of J. sabina coverage onα-diversity in a single-year, and its effects on the β-diversity of the plant community structure in the local ecosystem are still unclear. We compared environmental conditions and plant species composition inside and outside of 11 J. sabina patches to evaluate the effects of its coverage on the species diversity of the understory community structure through modifying microhabitat conditions. Water and nutrient conditions were higher inside the patches, whereas light conditions were higher outside. More perennial herbs and C3 plants were found inside and more annual herbs and C4 plants were found outside. There were different trends in α-diversity each year, while β-diversity was consistently greater inside the patches. This research suggests that the coverage of J. sabina can drive different community structures by providing heterogeneous environmental conditions, and would increase plant species diversity in the local ecosystem. en-copyright= kn-copyright= en-aut-name=QinLong en-aut-sei=Qin en-aut-mei=Long kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamabayashiAyaka en-aut-sei=Yamabayashi en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoTetsuya K. en-aut-sei=Matsumoto en-aut-mei=Tetsuya K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhangGuosheng en-aut-sei=Zhang en-aut-mei=Guosheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamanakaNorikazu en-aut-sei=Yamanaka en-aut-mei=Norikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirobeMuneto en-aut-sei=Hirobe en-aut-mei=Muneto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MikiNaoko H. en-aut-sei=Miki en-aut-mei=Naoko H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=College of Ecology and Environment, Inner Mongolia Agricultural University kn-affil= affil-num=5 en-affil=Arid Land Research Center, Tottori University kn-affil= affil-num=6 en-affil=Faculty of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Faculty of Environmental and Life Science, Okayama University kn-affil= en-keyword=Nurse plant kn-keyword=Nurse plant en-keyword=Plant species diversity kn-keyword=Plant species diversity en-keyword=Plant species coexistence kn-keyword=Plant species coexistence en-keyword=Plant–plant interactions kn-keyword=Plant–plant interactions en-keyword=Mu Us sandy land kn-keyword=Mu Us sandy land END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=5 article-no= start-page=530 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260428 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Photosynthetic Response of Larix gmelinii var. japonica Saplings After Exogenous Glutathione Foliar Application en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sapling survival and growth depend on photosynthetic assimilates. Therefore, improving physiological performance during early stages may enhance subsequent performance and nursery production. This study evaluated whether exogenous oxidized glutathione (GSSG), reported to enhance photosynthesis, improves the photosynthetic, physiological, and growth-related traits of Larix gmelinii var. japonica saplings. Sixteen saplings were assigned to four treatments: GSSG, 5-aminolevulinic acid, Hyponex, and a water control. Photosynthetic, nitrogen-related, and growth traits were measured before treatment and at 3, 6, 13, and 31 days after treatment, and biomass was assessed after three months. The GSSG treatment showed no difference in the net CO2 assimilation rate (Amax) compared with the control, but exhibited a significantly earlier peak at 6 days than the other treatments. This response was supported by the stability of GSSG-treated saplings against photoinhibition (Fv/Fm) and a tendency toward greater resilience to midday light stress (ΦPSII). Enhanced photosynthetic performance was associated with reduced carbon and nitrogen fluctuations and was accompanied by numerically greater root and stem biomass in the 2024 terminal shoots. Although fertilization effects were generally weak and transient, GSSG elicited notable responses, suggesting that the immediate enhancement of photosynthesis underlies its impact. However, its antioxidant properties under stressful conditions warrant further investigation. en-copyright= kn-copyright= en-aut-name=RahayuResa Sri en-aut-sei=Rahayu en-aut-mei=Resa Sri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshizukaWataru en-aut-sei=Ishizuka en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NaritaAyu en-aut-sei=Narita en-aut-mei=Ayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyataRie en-aut-sei=Miyata en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MikiNaoko H. en-aut-sei=Miki en-aut-mei=Naoko H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KonHirokazu en-aut-sei=Kon en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyazakiYuko en-aut-sei=Miyazaki en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil= Forestry Research Institute, Hokkaido Research Organization kn-affil= affil-num=3 en-affil= Forestry Research Institute, Hokkaido Research Organization kn-affil= affil-num=4 en-affil= Forestry Research Institute, Hokkaido Research Organization kn-affil= affil-num=5 en-affil= Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil= Forestry Research Institute, Hokkaido Research Organization kn-affil= affil-num=7 en-affil= Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=exogenous glutathione kn-keyword=exogenous glutathione en-keyword=foliar fertilizer kn-keyword=foliar fertilizer en-keyword=Larix gmelinii var. japonica kn-keyword=Larix gmelinii var. japonica en-keyword=photosystem II quantum yield kn-keyword=photosystem II quantum yield en-keyword=photosynthetic rate kn-keyword=photosynthetic rate END start-ver=1.4 cd-journal=joma no-vol=40 cd-vols= no-issue=6 article-no= start-page=e70582 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260528 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Risk Factors for Waiting List Mortality in Lung Transplant Candidates With Post‐Hematopoietic Stem Cell Transplantation Non‐Infectious Pulmonary Complications en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Late-onset non-infectious pulmonary complications (LONIPCs) following hematopoietic stem cell transplantation (HSCT) are a known indication for need of lung transplantation. This study aimed to clarify the clinical characteristics of patients with LONIPCs after HSCT who were registered for lung transplantation and reveal the risk factors for waiting list mortality.
Methods: We retrospectively reviewed the clinical data of patients with LONIPCs after allogeneic HSCT who were referred to Okayama University Hospital and registered in the Japan Organ Transplant Network for deceased-donor lung transplantation between 2005 and 2023. Pediatric patients aged <18 years at the time of registration were excluded.
Results: Thirty-four patients were included in this study. Notably, two distinct phenotypic groups were identified: One with a bronchiolitis obliterans pattern on high-resolution computed tomography and a mixed ventilatory defect, and the other with a pleuroparenchymal fibroelastosis pattern and a restrictive ventilatory defect. The median waiting duration for a deceased-donor lung transplant was 662 days, and 16 patients died during the waiting period. The cumulative incidence of waiting list mortality was 20.6% (95% confidence interval [CI], 8.9%–35.6%) at 1 year and 46.1% (95% CI, 27.8%–62.7%) at 3 years. A history of pneumothorax, greater dyspnea on exertion, and higher serum Krebs von den Lungen-6 levels were associated with an increased risk of waiting list mortality.
Conclusion: In patients with LONIPCs after HSCT, a history of pneumothorax may be a marker of a poor prognosis and could serve as a criterion for referral of lung transplantation. en-copyright= kn-copyright= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SenooSatoru en-aut-sei=Senoo en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MakimotoSatoko en-aut-sei=Makimoto en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaganoTomohiro en-aut-sei=Nagano en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoHaruchika en-aut-sei=Yamamoto en-aut-mei=Haruchika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MiyaharaNobuaki en-aut-sei=Miyahara en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=hematopoietic stem cell transplantation kn-keyword=hematopoietic stem cell transplantation en-keyword=late-onset non-infectious pulmonary complications kn-keyword=late-onset non-infectious pulmonary complications en-keyword=lung transplantation kn-keyword=lung transplantation en-keyword=pneumothorax kn-keyword=pneumothorax END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260526 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Optimizing low-dose rituximab protocol for ABO-mismatched kidney transplantation: long-term outcomes in a single-center retrospective cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background ABO-mismatched kidney transplantation (KTx) expands donor availability but increases risks of antibody-mediated rejection and passenger lymphocyte syndrome (PLS). While rituximab (Rit) potentially mitigates these complications, conventional high-dose regimens (375 mg/m2) elevate infectious and hematologic toxicity. We implemented low-dose Rit induction (200 mg/body) for desensitization in minor/major ABO-mismatched and DSA-positive KTx, evaluating its efficacy and safety over 15-years.
Methods This single-center retrospective cohort (May 2009–April 2024) analyzed 161 adult KTx recipients: Rit (n = 107) and Non-Rit (n = 54) groups. All received tacrolimus, mycophenolate mofetil, prednisolone, and basiliximab; high-risk patients also underwent plasmapheresis. Outcomes included graft survival, biopsy-proven acute rejection, de novo donor-specific antibody (DSA) formation, infection, severe neutropenia, and PLS.
Results 1-year graft survival was 100% in both groups. 5-year death-censored graft survival was 95.8% (Rit) vs 95.9% (Non-Rit), respectively (log-rank P = 0.43). Biopsy-proven acute rejection (7.5% vs 3.7%, P = 0.50) and de novo DSA production were equivalent (Class I: 5.5% vs 2.2%; Class II: 6.6% vs 8.7%; both P = 1.00), with lower mean fluorescent intensity (MFI) in the Rit group. Cytomegalovirus disease, urinary tract infection and fungal infection rates were comparable between both groups. Grade 4 neutropenia was not associated with Rit (OR 2.65; 95% CI 0.63–11.0; P = 0.18). Blood transfusion for hemoglobin declines occurred in 5.6% vs 7.4%, with preserved haptoglobin in all cases, indicating no PLS.
Conclusions Low-dose Rit induction achieves excellent graft survival and effective PLS prevention, without increasing toxicity, supporting its adoption as an optimal desensitization strategy. en-copyright= kn-copyright= en-aut-name=YamanoiTomoaki en-aut-sei=Yamanoi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SekitoTakanori en-aut-sei=Sekito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokunagaMoto en-aut-sei=Tokunaga en-aut-mei=Moto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=YoshinagaKasumi en-aut-sei=Yoshinaga en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaruyamaYuki en-aut-sei=Maruyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=KubotaRisa en-aut-sei=Kubota en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakeuchiHidemi en-aut-sei=Takeuchi en-aut-mei=Hidemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MorinagaHiroshi en-aut-sei=Morinaga en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=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 Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=3 en-affil=Department of Urology, NHO Okayama Medical Center 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 Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic 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, NHO Okayama Medical Center kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Urology, Shimane University Faculty 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=Kidney transplantation kn-keyword=Kidney transplantation en-keyword=ABO-mismatch kn-keyword=ABO-mismatch en-keyword=Low-dose rituximab kn-keyword=Low-dose rituximab en-keyword=Graft survival kn-keyword=Graft survival en-keyword=Passenger lymphocyte syndrome kn-keyword=Passenger lymphocyte syndrome 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, Universität 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=アスコクロリン誘導体はIL-9産生CD8T細胞を誘導する kn-title=Induction of IL-9-producing CD8+ T cells by ascochlorin derivatives en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=IMANONatsumi en-aut-sei=IMANO en-aut-mei=Natsumi kn-aut-name=今野なつみ kn-aut-sei=今野 kn-aut-mei=なつみ 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=20260526 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Treatment strategies for pulmonary arterial hypertension associated with adult congenital heart diseases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction
The number of patients with adult congenital heart disease (ACHD) is gradually increasing worldwide due to advances in surgical techniques and pharmacological therapies. ACHD can lead to pulmonary arterial hypertension (PAH), and treatment strategies for PAH associated with ACHD have also evolved.

Areas covered
Several PAH-targeted drugs including endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, and prostacyclin analogs are available for treatment of PAH. In this review, we summarized the current evidence regarding the use of PAH-targeted drugs in patients with PAH associated with ACHD. We also propose a ‘treat and repair’ strategy, which involves initial medical treatment to improve PAH followed by surgical or interventional repair of the systemic-to-pulmonary shunt. A PubMed literature search was conducted from 2000 to 2025.

Expert opinion
In cases of PAH associated with a systemic-to-pulmonary cardiac shunt, advanced PAH-targeted drugs can improve hemodynamics, and reduce the risk of cardiac defect repair and further improvement in PAH. The treat and repair strategy represents a promising therapeutic approach for PAH patients associated with systemic-to-pulmonary shunts. en-copyright= kn-copyright= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 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=5 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Adult congenital heart diseases kn-keyword=Adult congenital heart diseases en-keyword=pulmonary arterial hypertension kn-keyword=pulmonary arterial hypertension en-keyword=PAH-targeted drugs kn-keyword=PAH-targeted drugs en-keyword=systemic-to-pulmonary shunt kn-keyword=systemic-to-pulmonary shunt en-keyword=treat and repair strategy kn-keyword=treat and repair strategy 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=53 cd-vols= no-issue= article-no= start-page=e2026GL122541 end-page= 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=Discovery of Repeating Shallow Moonquakes in the Apollo Lunar Seismic Data en-subtitle= kn-subtitle= en-abstract= kn-abstract=Shallow moonquakes have been considered unique due to their large magnitudes and affinities with intraplate earthquakes. However, the small number of detections (<80 events) has prevented detailed characterization. In this study, I identified a pair of repeating shallow moonquakes by analyzing a recently updated moonquake data set. Relative-phase assessment revealed that these events exhibit a consistent fault-slip direction despite their occurrence at opposite tidal phases. This differs from what was observed for repeating deep moonquakes, which are closely related to tides, implying that tidal stress does not dominantly control fault-slip initiation of the repeating shallow moonquakes. Also, the identified repeating shallow moonquakes exhibit a similar relationship between seismic moment and the spatial scale of the slip area to earthquakes. This may indicate that earthquake-like fault physics operates on the Moon, albeit with a different driving mechanism than on Earth. en-copyright= kn-copyright= en-aut-name=OnoderaKeisuke en-aut-sei=Onodera en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= en-keyword=lunar seismology kn-keyword=lunar seismology en-keyword=tectonism kn-keyword=tectonism en-keyword=Moon kn-keyword=Moon en-keyword=Apollo kn-keyword=Apollo en-keyword=planetary seismology kn-keyword=planetary seismology en-keyword=fault physics kn-keyword=fault physics END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Second-look endoscopy does not reduce delayed bleeding after endoscopic papillectomy: a multicenter propensity score-matched analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Delayed bleeding is a frequent and serious complication after endoscopic papillectomy (EP). Second-look endoscopy (SLE) is often scheduled on the following day for wound assessment and prophylactic hemostasis, but its clinical value remains unclear.
Objectives: This study evaluated the effectiveness of SLE in preventing delayed bleeding after EP.
Design: This study was a multicenter, retrospective cohort study.
Methods: We retrospectively reviewed 132 consecutive patients who underwent EP at nine high-volume centers between 2003 and 2024 (SLE group, n = 73; non-SLE group, n = 59). Propensity score matching was performed to balance baseline characteristics. The primary outcome was delayed bleeding, and secondary outcomes were risk factors, the impact of prophylactic hemostasis during SLE, and hospital stay.
Results: After matching, 43 patients were included in each group. The incidence of delayed bleeding did not differ between the SLE and non-SLE groups (14% vs 9%, p = 0.50). Multivariate analysis identified a lack of preventive clipping closure as the only independent risk factor (odds ratio 15, 95% confidence interval 1.3–177, p = 0.030). Prophylactic hemostasis during SLE did not reduce bleeding but was associated with prolonged hospitalization (13 vs 9 days, p = 0.012).
Conclusion: Routine SLE after EP does not reduce delayed bleeding. Moreover, prophylactic hemostasis in asymptomatic patients may unnecessarily prolong hospitalization. Hemostasis should be reserved for patients who develop clinical signs of bleeding. en-copyright= kn-copyright= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UekiToru en-aut-sei=Ueki en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HimeiHitomi en-aut-sei=Himei en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakakiharaIchiro en-aut-sei=Sakakihara en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UetaEijiro en-aut-sei=Ueta en-aut-mei=Eijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyokawaTatsuya en-aut-sei=Toyokawa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaradaRyo en-aut-sei=Harada en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OgawaTaiji en-aut-sei=Ogawa en-aut-mei=Taiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TomodaTakeshi en-aut-sei=Tomoda en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatoHironari en-aut-sei=Kato en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 ORCID= affil-num=1 en-affil=Department of Endoscopy, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Endoscopy, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology, Fukuyama City Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Kagawa Prefectural Central Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=7 en-affil=Department of Gastroenterology, NHO Fukuyama Medical Center kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Japanese Red Cross Okayama Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology, Tsuyama Chuo Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=12 en-affil=Center for Innovative Clinical Medicine, Medical Development Field, Okayama University kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=19 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=delayed bleeding kn-keyword=delayed bleeding en-keyword=endoscopic papillectomy kn-keyword=endoscopic papillectomy en-keyword=post-resection site kn-keyword=post-resection site en-keyword=prophylactic hemostasis kn-keyword=prophylactic hemostasis en-keyword=second-look endoscopy kn-keyword=second-look endoscopy 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=7 cd-vols= no-issue=2 article-no= start-page=9 end-page= 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=Relationship Between Numbers of Patients Registered and Procedures Performed at Lung Transplantation Centers in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Recently, there has been a dramatic increase in deceased lung transplantation (DLT) procedures performed in Japan. However, there is concern that the number of transplantations may reach the limit of capacity in some centers. The present study was conducted to analyze the relationship between the numbers of individuals registered for DLT by the Japan Organ Transplantation Network (JOT) and procedures subsequently performed at lung transplantation centers. Methods: Using a database and registry reports provided by the Japanese Society of Lung and Heart-lung Transplantation, the numbers of individuals registered in the JOT and DLT procedures performed from January 2014 to December 2023 were analyzed. Results: The number of registrations was found to be correlated with the number of DLTs, with the coefficient of determination (R2) 0.962 and slope of the regression line (X coefficient) 0.407. The facility with the greatest number of registrations, with a registration-to-transplantation ratio of 0.353, was identified as an outlier (p < 0.05) and excluded from analysis. This exclusion increased both the correlation coefficient value to 0.986 and X coefficient value to 0.461. Conclusions: The present analysis showed that the number of DLTs was well correlated with number of registrations at each of the transplantation facilities. Both registration and transplantation numbers have increased in the recent decade. The facility with the highest number of registrations showed a lower registration-to-transplantation ratio, because the increase in registrations outpaced the number of transplantations. en-copyright= kn-copyright= en-aut-name=InoueTakashi en-aut-sei=Inoue en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChidaMasayuki en-aut-sei=Chida en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkadaYoshinori en-aut-sei=Okada en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoMasaaki en-aut-sei=Sato en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiHidemi en-aut-sei=Suzuki en-aut-mei=Hidemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoshikawaYasushi en-aut-sei=Hoshikawa en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Chen-YoshikawaToyofumi en-aut-sei=Chen-Yoshikawa en-aut-mei=Toyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakajimaDaisuke en-aut-sei=Nakajima en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SintaniYasushi en-aut-sei=Sintani en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SatoToshihiko en-aut-sei=Sato en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShiraishiTakeshi en-aut-sei=Shiraishi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MatsumotoKeitaro en-aut-sei=Matsumoto en-aut-mei=Keitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakajimaTakahiro en-aut-sei=Nakajima en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MaedaSumiko en-aut-sei=Maeda en-aut-mei=Sumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery, School of Medicine, Dokkyo Medical University kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery, School of Medicine, Dokkyo Medical University kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, University of Tokyo kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery, Chiba University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Fujita Health University School of Medicine kn-affil= affil-num=7 en-affil=Department of Thoracic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Thoracic Surgery, Kyoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, The Osaka University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama kn-affil= affil-num=12 en-affil=Department of General Thoracic, Breast and Pediatric Surgery, Fukuoka University School of Medicine kn-affil= affil-num=13 en-affil=Department of General Thoracic, Breast and Pediatric Surgery, Fukuoka University School of Medicine kn-affil= affil-num=14 en-affil=Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=15 en-affil=Department of General Thoracic Surgery, School of Medicine, Dokkyo Medical University kn-affil= affil-num=16 en-affil=Department of General Thoracic Surgery, School of Medicine, Dokkyo Medical University kn-affil= en-keyword=lung transplantation kn-keyword=lung transplantation en-keyword=registration kn-keyword=registration en-keyword=registration-to-transplantation ratio kn-keyword=registration-to-transplantation ratio en-keyword=ransplantation center kn-keyword=ransplantation center 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=20260520 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Appropriate dose reduction using photon-counting detector CT for temporal bone imaging: phantom and clinical studies with helical acquisition en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: To determine the extent of possible dose reduction with photon-counting detector computed tomography (PCD-CT) while maintaining image quality equivalent to that of energy-integrating detector CT (EID-CT) images at standard dose in the temporal bone.
Materials and methods: PCD-CT and EID-CT imaging quality were compared by visual evaluation of clinical temporal bone images and visual scores with Welch’s t-test at standard dose. A head phantom was used to evaluate imaging quality under dose reduction. The detectability index (d’) of the PCD-CT images at various dose levels and the EID-CT images at standard dose was evaluated. Dose reduction limit with PCD-CT used in the subsequent clinical evaluation was determined as the lowest dose with image quality equal to or better than EID-CT. The clinical equivalence of PCD-CT image quality at the determined reduced dose to that with EID-CT at standard dose was evaluated using visual scores. Equivalence was determined if the 95% confidence intervals of differences did not exceed the equivalence margin of ±1.
Results: At standard doses, PCD-CT images demonstrated significantly higher visual scores than EID-CT images (3.73 vs. 2.56 for incudomalleolar joint, 3.75 vs. 2.63 for stapes, 3.54 vs. 2.52 for cochlea, and 3.58 vs. 2.46 for facial nerve canal; all P 0.001). In the phantom study, the d’ value was 0.15 with EID-CT at standard dose and was 0.12 and 0.17 with PCD-CT at 25% and 50% of the standard dose, respectively. Clinically, the mean visual scores of PCD-CT images at 50% of the standard dose were equivalent to EID-CT images at standard dose in all regions (3.58 vs. 3.12 for incudomalleolar joint, 3.46 vs. 3.19 for stapes, 3.50 vs. 3.08 for cochlea, 3.58 vs. 3.27 for facial nerve canal).
Conclusion: PCD-CT may preserve image quality even at 50% of the standard dose in the temporal bone. en-copyright= kn-copyright= en-aut-name=TakahashiYuka en-aut-sei=Takahashi en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HigakiFumiyo en-aut-sei=Higaki en-aut-mei=Fumiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraYuko en-aut-sei=Nakamura en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HigakiToru en-aut-sei=Higaki en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugayaAkiko en-aut-sei=Sugaya en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KitayamaTakahiro en-aut-sei=Kitayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorimitsuYusuke en-aut-sei=Morimitsu en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=InoueTomohiro en-aut-sei=Inoue en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkagiNoriaki en-aut-sei=Akagi en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsuiYusuke en-aut-sei=Matsui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=AwaiKazuo en-aut-sei=Awai en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Diagnostic Radiology, Hiroshima University kn-affil= affil-num=4 en-affil=Graduate School of Advanced Science and Engineering, Hiroshima University kn-affil= affil-num=5 en-affil=Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Center for Innovative Clinical Medicine, Okayama University kn-affil= affil-num=7 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=8 en-affil=Department of Radiological Technology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Radiological Technology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Radiological Technology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Radiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Diagnostic Radiology, Hiroshima University kn-affil= affil-num=14 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=PCD-CT kn-keyword=PCD-CT en-keyword=EID-CT kn-keyword=EID-CT en-keyword=Dose reduction kn-keyword=Dose reduction en-keyword=Temporal bone CT kn-keyword=Temporal bone CT en-keyword=Incudomalleolar joint kn-keyword=Incudomalleolar joint en-keyword=Stapes kn-keyword=Stapes END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=2 article-no= start-page=e70136 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exogenous Glutathione and Nitric Oxide Improve Waterlogging Stress Tolerance in Maize en-subtitle= kn-subtitle= en-abstract= kn-abstract=Maize (Zea mays L.) is one of the major grain crops worldwide that is particularly vulnerable to waterlogging (WL) stress. Glutathione (GSH) and nitric oxide (NO) are known to protect plants from a variety of abiotic stresses; however, their potential for improving WL tolerance in maize remains unexplored. The present study examined the impact of exogenously applied GSH and NO on maize plants exposed to WL-stress. Our findings revealed that GSH + NO-treated waterlogged maize plants grew better and produced more biomass than only WL-stressed plants. The improved performance of GSH + NO-sprayed WL-stressed maize seedlings was supported by the increased root dry and fresh weight, shoot length, shoot dry and fresh weight, chlorophyll a, chlorophyll b, and carotenoid content. Exogenous GSH and NO treatments significantly enhanced the amounts of leaf proline, leaf soluble sugars, and total protein in maize seedlings, suggesting adaptive metabolic reprogramming under stress. The increased malondialdehyde (MDA) levels and accumulation of hydrogen peroxide (H2O2) in maize leaves and roots revealed that WL caused significant oxidative damage. Exogenous GSH, NO individually, and combinedly significantly decreased total H2O2 and MDA contents in both leaves and roots. Exogenous GSH and NO reduced oxidative stress by increasing peroxidase activity, ascorbic acid, and anthocyanin content in maize leaf and root tissues. Our findings emphasize the possible relevance of GSH and NO, simultaneously and individually, in enhancing adaptive mechanisms in maize seedlings for reducing WL-induced damage. Although the GSH + NO-mediated approach shows promise for mitigating WL-stress in maize under controlled conditions, further field-based investigations are required to validate its practical applicability. en-copyright= kn-copyright= en-aut-name=AngonProdipto Bishnu en-aut-sei=Angon en-aut-mei=Prodipto Bishnu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Tahjib‐Ul‐ArifMd. en-aut-sei=Tahjib‐Ul‐Arif en-aut-mei=Md. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JahanMd. Sarwar en-aut-sei=Jahan en-aut-mei=Md. Sarwar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HasanMd. Mahadi en-aut-sei=Hasan en-aut-mei=Md. Mahadi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurataYoshiyuki en-aut-sei=Murata en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Applied Plant Biology and Bioinformatics Lab, Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University kn-affil= affil-num=2 en-affil=Applied Plant Biology and Bioinformatics Lab, Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University kn-affil= affil-num=3 en-affil=Applied Plant Biology and Bioinformatics Lab, Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University kn-affil= affil-num=4 en-affil=Basic and Applied Scientific Research Centre, Imam Abdulrahman Bin Faisal University kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=crop improvement kn-keyword=crop improvement en-keyword=glutathione kn-keyword=glutathione en-keyword=maize kn-keyword=maize en-keyword=nitric oxide kn-keyword=nitric oxide en-keyword=stress tolerance kn-keyword=stress tolerance END start-ver=1.4 cd-journal=joma no-vol=367 cd-vols= no-issue= article-no= start-page=199724 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=Mycoviruses diversity in the black kōji mold, Aspergillus luchuensis (section Nigri) isolated from liquor-production environments in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Some fungal species in the genus Aspergillus are economically important due to their role in the production of liquors and various foods; however, their viromes, which may affect their performance, remain unexplored. Therefore, this study examined the viromes of nine strains of Aspergillus luchuensis (section Nigri), the black kōji mold used in the production of shochu (a traditional Japanese liquor) in Japan. It identified virus-like sequences related to alterna-, partiti-, curvula, botourmia-, narna-like, and umbra-like viruses. Some sequences appear to represent new variants (e.g., alterna- and gammapartitiviruses), while many others correspond to novel viral species within established or proposed mycoviral families. All A. luchuensis strains harbored multiple virus infections, with 2 to 7 viruses per strain. Three alternavirus strains with four-segmented double-stranded RNA (dsRNA) genomes were confirmed, along with minor variants co-present with the predominant strains. Notably, a gammapartitivirus appears to have two additional dsRNA genome segments, along with two satellite-like short dsRNA segments in some fungal isolates. Furthermore, at least five short RNAs (0.48–1.31 kb) were identified, three of which are possibly satellite-like RNAs associated with novel single-stranded RNA viruses (botourmia- and umbra-like viruses). These findings reveal the great diversity of mycoviruses in A. luchuensis populations and lay the foundation for further investigation into their impact on fungal phenotypes and liquor production. en-copyright= kn-copyright= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NanajiMisaki en-aut-sei=Nanaji en-aut-mei=Misaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugaharaHitomi en-aut-sei=Sugahara en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujitaMiki en-aut-sei=Fujita en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AndikaIda Bagus en-aut-sei=Andika en-aut-mei=Ida Bagus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FumihiroFujimori en-aut-sei=Fumihiro en-aut-mei=Fujimori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Tokyo Kasei 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=Northwest A&F University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Tokyo Kasei University kn-affil= en-keyword=Aspergillus luchuensis kn-keyword=Aspergillus luchuensis en-keyword=Section Nigri kn-keyword=Section Nigri en-keyword=Mycovirus kn-keyword=Mycovirus en-keyword=RNA-seq kn-keyword=RNA-seq en-keyword=Virus population kn-keyword=Virus population en-keyword=Genome segment kn-keyword=Genome segment en-keyword=Fermentation kn-keyword=Fermentation en-keyword=Island kn-keyword=Island END start-ver=1.4 cd-journal=joma no-vol=185 cd-vols= no-issue=6 article-no= start-page=391 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260513 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Drug-induced sarcoidosis-like reaction following IL-4/IL-13 receptor blockade by dupilumab en-subtitle= kn-subtitle= en-abstract= kn-abstract=The purpose of the study is to review reported cases of dupilumab-associated drug-induced sarcoidosis-like reaction (DISR) and consider possible immunologic mechanisms. This short review aims to raise awareness of dupilumab-associated DISR and discuss safety considerations in pediatric patients.
Conclusion: Dupilumab is a human monoclonal antibody that reduces inflammation driven by T helper 2 (Th2) cells and is used to treat type 2 inflammatory disorders, including atopic dermatitis. The most common adverse reactions during the first year of treatment are local reactions at the injection site, conjunctivitis, and headache. Although DISR is rare, it has been documented in dupilumab-treated patients. We hypothesized that dupilumab shifts the Th1/Th2 equilibrium toward Th1 and granulomatous inflammation, which may present as DISR. We identified and reviewed 10 recently reported DISR cases and observed that reported features of DISR—including uveitis, optic neuritis and meningoencephalitis, bilateral hilar lymphadenopathy, and histopathologically noncaseating granulomas—can mimic systemic sarcoidosis. Discontinuation of dupilumab resulted in favorable outcomes in most reported DISR cases; however, symptoms worsened in some cases and sequelae became a concern. Case reports of DISR have so far been limited to adults or adolescents, but awareness of potential adverse effects of dupilumab remains important in pediatric patients. en-copyright= kn-copyright= en-aut-name=YasuiKozo en-aut-sei=Yasui en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= affil-num=1 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Okayama University Hospital Center for Innovative Clinical Medicine kn-affil= en-keyword=Dupilumab kn-keyword=Dupilumab en-keyword=Sarcoidosis kn-keyword=Sarcoidosis en-keyword=IL-4 kn-keyword=IL-4 en-keyword=IL-13 kn-keyword=IL-13 en-keyword=Th1-Th2 balance kn-keyword=Th1-Th2 balance 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-Fe₃C-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 Fe₃C 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/m³, with tighter constraints for models featuring an Fe₃C core.
At Mercury-relevant pressures, either Fe or Fe₇C₃ 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/m³. 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=Muséum National d’Histoire Naturelle, Sorbonne Université, UMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC kn-affil= affil-num=4 en-affil=Muséum National d’Histoire Naturelle, Sorbonne Université, UMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux 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=53 cd-vols= no-issue=9 article-no= start-page=e2025GL121619 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Apollo 17 Lunar Surface Gravimeter as a Seismometer: Relocating Shallow‐Moonquake Sources and Implications for Source Mechanism en-subtitle= kn-subtitle= en-abstract= kn-abstract=Among the reported seismic events on the Moon, shallow moonquakes are known for their unique features, such as high-frequency energy excitation, similarity to intraplate earthquakes, and the largest energy release of all reported moonquakes. Despite these interesting features, a small number of samples (<80 events) and sparse seismic network observations prevented us from gaining an in-depth understanding of shallow moonquakes. In this study, by using the Apollo 17 gravimeter as a pseudo-seismometer, we extend the Apollo lunar seismic network and located a few shallow moonquakes more accurately. In addition, comparing the located shallow-moonquake epicenters with surface/subsurface geological features indicates that at least one event may be better explained by deep-seated faults within the crust. Along with a previous demonstration of low-frequency moonquakes, our analysis of high-frequency events shows that the Apollo 17 gravimeter can serve as a seismometer over a broader frequency range than previously considered. en-copyright= kn-copyright= en-aut-name=OnoderaKeisuke en-aut-sei=Onodera en-aut-mei=Keisuke 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= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Institut de Physique du Globe de Paris, Université Paris Cité kn-affil= en-keyword=Moon kn-keyword=Moon en-keyword=lunar seismology kn-keyword=lunar seismology en-keyword=tectonism kn-keyword=tectonism en-keyword=moonquake kn-keyword=moonquake 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=20260506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Feasibility of Comprehensive Genomic Profiling for Biliary Tract Cancer Using Transpapillary Biopsy Samples: A Prospective Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Patients with biliary tract cancer (BTC) often have actionable mutations, and comprehensive genomic profiling (CGP) plays an important role. However, the feasibility of CGP using transpapillary biopsy (TPB) samples remains unclear.
Methods: Thirty patients with suspected BTC based on radiographic imaging were enrolled. Pre-analytical criteria for CGP suitability were based on the OncoGuide NCC Oncopanel System (NCCOP) and FoundationOne CDx (F1CDx). Each patient underwent six biopsies using an endoscopic introducer: five biopsy samples were preserved as formalin-fixed paraffin-embedded (FFPE) samples and one as a fresh frozen (FF) sample. DNA quality indicators were compared between the two groups.
Results: Malignancy was confirmed in 29 patients, and one had a benign biliary stricture. Suitability rate was 31% (9/29) for NCCOP and 3.4% (1/29) for F1CDx. Compared to FFPE samples, FF samples demonstrated significantly higher DNA concentration [ng/μL, interquartile range (IQR)], [0.34 (0.16–0.95) vs. 37.8 (11.6–67.6), p < 0.001] and DNA integrity number (IQR) [7.1 (6.8–7.3) vs. 8.9 (8.3–9), p = 0.021].
Conclusions: Introducer-assisted multipass TPB may increase the rate of obtaining adequate CGP specimens, but its suitability remains limited and strongly panel dependent. Since FF samples have better DNA quality, establishing a system detailing their use is desirable.
Trial Registration: ClinicalTrials.gov identifier: UMIN 000049826 en-copyright= kn-copyright= en-aut-name=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya 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=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=InoueHirohumi en-aut-sei=Inoue en-aut-mei=Hirohumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Endoscopy, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Medical Support, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Endoscopy, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Endoscopy, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=biliary tract cancer kn-keyword=biliary tract cancer en-keyword=biopsy kn-keyword=biopsy en-keyword=DNA kn-keyword=DNA en-keyword=endoscopic retrograde cholangiopancreatography kn-keyword=endoscopic retrograde cholangiopancreatography en-keyword=genetic profile kn-keyword=genetic profile END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=3 article-no= start-page=e70554 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An Atypical Surgical Case of Lung Cancer With Unilateral Absence of the Pulmonary Artery, With Only the Superior Branch Remaining en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 69-year-old woman was referred to our department for an abnormal shadow on chest radiography. Contrast-enhanced computed tomography (CT) revealed a solid nodule in the right lower lobe and defects in the branches of the middle and lower lobes of the pulmonary artery (PA). Furthermore, collateral circulation had developed via the right internal thoracic, bronchial, intercostal, inferior phrenic, and subdiaphragmatic arteries. The solid nodule was diagnosed as adenocarcinoma by CT-guided biopsy. The day before surgery, embolization was performed using interventional radiology (IVR) to mitigate the risk of bleeding during thoracotomy, resulting in minimal intraoperative bleeding during the subsequent right middle and lower lobectomies with lymph node dissection (ND2a-1). UAPA is a rare congenital abnormality characterized by unilateral pulmonary artery agenesis. The presence of recurrent infections, extensive intrathoracic adhesions, and developed collateral circulation may pose challenges during surgical procedures. en-copyright= kn-copyright= en-aut-name=OkadaKazuhiro en-aut-sei=Okada en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RyukoTsuyoshi en-aut-sei=Ryuko en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=interventional radiology kn-keyword=interventional radiology en-keyword=lung cancer kn-keyword=lung cancer en-keyword=unilateral absence of the pulmonary artery kn-keyword=unilateral absence of the pulmonary artery END start-ver=1.4 cd-journal=joma no-vol=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=DrilleauMélanie en-aut-sei=Drilleau en-aut-mei=Mélanie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LognonnéPhilippe en-aut-sei=Lognonné 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=Université Paris Cité, Institut de physique du globe de Paris, CNRS kn-affil= affil-num=2 en-affil=Université Paris Cité, Institut de physique du globe de Paris, CNRS kn-affil= affil-num=3 en-affil=Université Paris Cité, Institut de physique du globe de Paris, CNRS kn-affil= affil-num=4 en-affil=Université Paris Cité, Institut de physique du globe de Paris, CNRS kn-affil= affil-num=5 en-affil=Université Paris Cité, Institut de physique du globe de Paris, CNRS kn-affil= affil-num=6 en-affil=Université Paris Cité, 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= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260429 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CDPKs as Ca2+ signaling decoders in guard cell signaling en-subtitle= kn-subtitle= en-abstract= kn-abstract=Stomatal movements are essential for balancing photosynthetic carbon dioxide uptake with water conservation and defense against pathogens. These processes are controlled by complex signaling networks in guard cells, in which calcium ions (Ca2+) act as a ubiquitous second messenger. Although stimulus-specific Ca2+ signatures have been well documented, how these signals are decoded into distinct physiological responses remains a central question in plant biology. Increasing evidence highlights calcium-dependent protein kinases (CDPKs) as key signal decoders in guard cell signaling. This mini-review summarizes recent advances in our understanding of how CDPKs perceive and translate Ca2+ fluctuations into stomatal responses. We focus on the roles of CDPKs in signaling pathways triggered by diverse stimuli, including phytohormones such as abscisic acid ABA, jasmonates, and salicylic acid, as well as biotic cues such as microbe- or pathogen-associated molecular patterns (MAMPs/PAMPs) and pathogen infection. We also discuss how gaseous signals and metabolic cues are integrated into CDPK-mediated pathways. In addition to their established role as downstream decoders of Ca2+ signals, emerging studies suggest that CDPKs can act upstream of Ca2+ oscillations and may also function through Ca2+-independent mechanisms. Together, these findings highlight the context-dependent and integrative roles of CDPKs in regulating stomatal behavior, contributing to plant fitness under fluctuating environmental conditions. en-copyright= kn-copyright= en-aut-name=MoriIzumi C. en-aut-sei=Mori en-aut-mei=Izumi C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Ca2+ signaling kn-keyword=Ca2+ signaling en-keyword=CDPK kn-keyword=CDPK en-keyword=Signal decoding kn-keyword=Signal decoding en-keyword=Stomata kn-keyword=Stomata END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue= article-no= start-page=2026010 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=Supplementation of 5-Aminolevulinic Acid Suppressed Body Weight Loss and Reduced Disease Severity During Eimeria tenella Infection in Broiler Chickens en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study aimed to evaluate the effects of 5-aminolevulinic acid (5-ALA) supplementation in broiler chickens infected with Eimeria tenella. To assess these effects, chickens supplemented with 20 ppm 5-ALA (5-ALA group) were compared with non-supplemented controls (control group). Sporulated E. tenella oocysts (2.0 × 103 oocysts per animal) were administered orally to 2-week-old broiler chickens. Body weight was measured weekly, and fecal samples were collected daily from 4 to 15 days post-infection (dpi). Fecal oocyst shedding was quantified using the sucrose flotation method. Cecal tissues were collected at 5 dpi for histopathological analysis and lesion scoring. The animals in the 5-ALA group exhibited significantly greater weight gain and milder clinical signs than those in the control group. Fecal oocyst shedding was highest at 7 dpi in both groups; however, the 5-ALA group exhibited significantly lower oocyst output than the control group. The total number of fecal oocysts shed during the acute infection period was significantly lower in the 5-ALA group than in the control group. Histopathological analysis revealed that although both groups exhibited epithelial hyperplasia and E. tenella schizonts in the cecal submucosa, inflammatory cell infiltration, cecal tissue damage, and histological lesion scores were significantly lower in the 5-ALA group than in the control group. These results suggest that 5-ALA supplementation may mitigate the clinical, parasitological, and histological effects of E. tenella infection in broiler chickens. en-copyright= kn-copyright= en-aut-name=HanifTaqi Ahmad en-aut-sei=Hanif en-aut-mei=Taqi Ahmad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsubayashiMakoto en-aut-sei=Matsubayashi en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HatabuToshimitsu en-aut-sei=Hatabu en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Laboratory of Animal Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Veterinary Science, Graduate School of Veterinary Sciences, Osaka Metropolitan University kn-affil= affil-num=3 en-affil=Laboratory of Animal Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=5-aminolevulinic acid kn-keyword=5-aminolevulinic acid en-keyword=avian coccidiosis kn-keyword=avian coccidiosis en-keyword=broilers kn-keyword=broilers END