start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=30805 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cinnamyl alcohol dehydrogenase (CAD) underlies the orange lemma trait and lignin reduction in barley en-subtitle= kn-subtitle= en-abstract= kn-abstract=Barley (Hordeum vulgare L.) is one of the worldfs major cereal crops and is widely used for feed, brewing, and food. Reducing lignin content in barley grain and straw is beneficial for improving forage digestibility and enhancing the efficiency of bioethanol production. The orange lemma mutation?characterized by orange pigmentation of husks and nodes?has long been associated with altered lignin metabolism; however, its genetic basis has remained unclear. We show that Cinnamyl Alcohol Dehydrogenase (CAD) is the causal gene underlying the orange lemma phenotype in barley. Genetic mapping using a eHaruna Nijof?~?eL053f F? population and the Barley 50 K SNP array defined a candidate region on chromosome 6H containing the CAD gene. Sequence analysis revealed that all orange lemma mutants, including both naturally occurring and EMS-induced lines, carried nucleotide changes in the CAD gene, resulting in amino acid substitutions or premature stop codons. Furthermore, CRISPR/Cas9-mediated knockout of CAD in the cultivar eGolden Promisef reproduced the orange lemma phenotype, providing functional validation. The knockout plants also showed significantly lower lignin content than wild-type plants. These findings resolve a long-standing question regarding the genetic basis of the orange lemma trait and demonstrate that disruption of CAD alters lignin accumulation in barley. This work provides a valuable genetic resource for breeding barley cultivars with improved biomass utilization for feed and bioenergy applications. en-copyright= kn-copyright= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoritaMaho en-aut-sei=Morita en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamajiNami en-aut-sei=Yamaji en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KakoRinka en-aut-sei=Kako en-aut-mei=Rinka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UshijimaTomokazu en-aut-sei=Ushijima en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Agricultural Science, Setsunan University kn-affil= affil-num=5 en-affil=Graduate School of Agricultural Science, Setsunan University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Cinnamyl Alcohol Dehydrogenase (CAD) kn-keyword=Cinnamyl Alcohol Dehydrogenase (CAD) en-keyword=Barley kn-keyword=Barley en-keyword=Orange lemma kn-keyword=Orange lemma en-keyword=Lignin kn-keyword=Lignin en-keyword=Genome editing kn-keyword=Genome editing END start-ver=1.4 cd-journal=joma no-vol= 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=7 cd-vols= no-issue=1 article-no= start-page=742 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260914 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rapid fluvial response to meter-scale coseismic coastal uplift during the 2024 Noto Peninsula earthquake en-subtitle= kn-subtitle= en-abstract= kn-abstract=The response of river profiles to relative base-level change is a key topic in earth surface processes, but observations capturing these changes on unconsolidated deposits at a 1?10 years timescales are scarce. We monitored geomorphic changes at the Hakka River mouth after the 3.5-meter base-level fall caused by coseismic uplift of the 2024 Noto Peninsula earthquake, Japan. Utilizing uncrewed aerial vehicle surveys, we documented a maximum vertical riverbed lowering of 2?m and knickpoint upstream migration of 770-m within the first-year post-earthquake, primarily triggered by erosion during major floods that followed the earthquake. Our findings demonstrate that fluvial terraces can develop within a year or less, following co-seismic coastal uplift. However, the river has not yet reached a renewed graded stage because riverbed armoring resulting from sediment sorting during incision currently inhibits further incision. We suggest that the abandonment of alluvial plains and lowering and widening of the riverbed in the lower 10-km segment will continue over the next decade. en-copyright= kn-copyright= en-aut-name=TakahashiTakayuki en-aut-sei=Takahashi en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OguraTakuro en-aut-sei=Ogura en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IizukaKotaro en-aut-sei=Iizuka en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwasaYoshiya en-aut-sei=Iwasa en-aut-mei=Yoshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HayakawaYuichi S. en-aut-sei=Hayakawa en-aut-mei=Yuichi S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AokiTatsuto en-aut-sei=Aoki en-aut-mei=Tatsuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MattaNobuhisa en-aut-sei=Matta en-aut-mei=Nobuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=International Research Institute of Disaster Science, Tohoku University kn-affil= affil-num=2 en-affil=Graduate School of Social Sciences, Hitotsubashi University kn-affil= affil-num=3 en-affil=Center for Spatial Information Science, The University of Tokyo kn-affil= affil-num=4 en-affil=Faculty of Education, University of Teacher Education Fukuoka kn-affil= affil-num=5 en-affil=Center for Spatial Information Science, The University of Tokyo kn-affil= affil-num=6 en-affil=Institute of Human and Social Sciences, Kanazawa University kn-affil= affil-num=7 en-affil=Graduate School of Education, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=1 article-no= start-page=37 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20261001 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Delta morphology reveals timings of early ocean regression and hydrologic shift on ancient Mars en-subtitle= kn-subtitle= en-abstract= kn-abstract=Marsf ancient hydrologic history remains a subject of debate, with competing interpretations suggesting either a large ocean or scattered lacustrine environments. Here, we show that delta morphology on Mars records a shift between these hydrologic regimes. Through controlled tank experiments, we identify two distinct delta types: globe-extruding deltash formed during water-level falls and gstepped fan-deltash formed during rising water levels. The lobe-extruding deltas occur near proposed paleo-coastlines and are dated to ~3.8?3.2 Ga, consistent with the existence of a Late Noachian?Hesperian ocean and its subsequent regression in the Late Hesperian. In contrast, stepped fan-deltas are found at a wider range of elevations and exhibit significantly younger ages (~2.1?0.1 Ga), suggesting episodic, localized lake formation during the Amazonian. Our findings constrain the timing of the planetary-scale transition from a global hydrosphere to localized aqueous environments and refine the understanding of Marsf paleoclimate evolution and potential habitability. en-copyright= kn-copyright= en-aut-name=KitoRen en-aut-sei=Kito en-aut-mei=Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HasegawaHitoshi en-aut-sei=Hasegawa en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RujTrishit en-aut-sei=Ruj en-aut-mei=Trishit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MutoTetsuji en-aut-sei=Muto en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OriGian Gabriele en-aut-sei=Ori en-aut-mei=Gian Gabriele kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KomatsuGoro en-aut-sei=Komatsu en-aut-mei=Goro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Science and Technology, Kochi University kn-affil= affil-num=3 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=4 en-affil=Department of Environmental Science, Nagasaki University kn-affil= affil-num=5 en-affil=International Research School of Planetary Sciences, Universit? dfAnnunzio kn-affil= affil-num=6 en-affil=International Research School of Planetary Sciences, Universit? dfAnnunzio kn-affil= END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=6 article-no= start-page=315 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260527 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Limited Immune-Mediated Efficacy of Anti-PD-L1/VEGF in EGFR-TKI-Na?ve Egfr-Mutant Lung Cancer with Non-Inflamed Tumor Microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immune checkpoint inhibitors (ICIs) show limited efficacy in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma due to its non-inflamed tumor microenvironment (TME). While quadruple therapy combining chemotherapy, anti-programmed death-ligand 1 (PD-L1), and anti-vascular endothelial growth factor (VEGF) antibodies has shown inconsistent results in EGFR-tyrosine kinase inhibitor (TKI)-pretreated patients, whether anti-VEGF therapy can modulate the intrinsic non-inflamed TME remains unknown. We employed an EGFR-TKI-na?ve syngeneic Egfr-mutant mouse model and evaluated effects of anti-VEGF, anti-PD-L1, carboplatin, and paclitaxel as monotherapies and combinations, with TME analysis via immunohistochemistry (IHC), flow cytometry, and RNA sequencing. Anti-PD-L1 showed no antitumor effect, and adding anti-VEGF failed to convert the TME to an inflamed status. Although paclitaxel?but not carboplatin?combined with low-dose anti-VEGF inhibited tumor growth, adding anti-PD-L1 provided no benefit, indicating the anti-VEGF-A antibody evaluated here has a limited role in sensitizing tumors to anti-PD-L1 regardless of chemotherapy. CD8+ T-cell depletion did not attenuate the effect of paclitaxel plus low-dose anti-VEGF, and IHC and RNA sequencing revealed increased natural killer cell infiltration, suggesting a CD8+ T-cell-independent, innate immune mechanism. These findings provide preclinical evidence that the evaluated anti-VEGF has limited immunomodulatory activity in EGFR-TKI-na?ve Egfr-mutant tumors with a non-inflamed TME, and suggest immunotherapeutic strategies beyond CD8+ T-cell-mediated immunity warrant investigation. en-copyright= kn-copyright= en-aut-name=HirabaeAtsuko en-aut-sei=Hirabae en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkawaSachi en-aut-sei=Okawa en-aut-mei=Sachi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakasukaTakamasa en-aut-sei=Nakasuka en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishimuraJun en-aut-sei=Nishimura en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SugimotoMasamichi en-aut-sei=Sugimoto en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Product Research Department, Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=15 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=EGFR mutation kn-keyword=EGFR mutation en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=syngeneic mouse model kn-keyword=syngeneic mouse model en-keyword=antitumor immunity kn-keyword=antitumor immunity en-keyword=non-inflamed tumor kn-keyword=non-inflamed tumor en-keyword=VEGF kn-keyword=VEGF en-keyword=PD-L1 kn-keyword=PD-L1 END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=10 article-no= start-page=e70299 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Interstitial Lung Disease in Patients With Unresectable Stage III NSCLC Treated With Chemoradiotherapy Followed by Durvalumab in Japan: Analysis From the Multicenter Prospective AYAME Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Interstitial lung disease (ILD) is a concerning adverse event associated with immune checkpoint inhibitors, including durvalumab. This analysis of the multicenter AYAME study assessed the longterm safety of durvalumab, focusing on ILD.
Methods: AYAME enrolled patients prescribed durvalumab for unresectable stage III non-small cell lung cancer (NSCLC) after chemoradiotherapy (CRT) from July 2019 to December 2020 in Japan. Patients received durvalumab for ??12?months and were prospectively followed for 3?years. Incidence, severity, and management of ILD were examined. Multivariable logistic regression analysis was conducted to investigate the association of patient characteristics with grade ??2 ILD occurrence.
Results: Of 511 patients in the safety analysis population, ILD occurred in 383 patients (75.0%) from durvalumab initiation to subsequent treatment start; median time to occurrence was 44.0?days. ILD led to permanent durvalumab discontinuation in 121/383 patients (31.6%), dose interruption in 111/383 (29.0%), and corticosteroid intervention in 168/383 (43.9%). Grade ??2 ILD occurrence was higher in patients with volume of lung parenchyma that received 20?Gy (V20) ??25% versus Conclusions: This study of durvalumab for NSCLC after CRT in a real-world setting indicated factors associated with grade ??2 ILD and provided valuable insights into ILD management strategies. These findings may contribute to establishing effective approaches to minimize ILD risk in practice.
Trial Registration: UMIN000037090/NCT03995875 en-copyright= kn-copyright= en-aut-name=YamamotoNobuyuki en-aut-sei=Yamamoto en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KenmotsuHirotsugu en-aut-sei=Kenmotsu en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkdemirBurak en-aut-sei=Akdemir en-aut-mei=Burak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UematsuShinya en-aut-sei=Uematsu en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuiAyako en-aut-sei=Fukui en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KotoRyo en-aut-sei=Koto en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiwaraMasakazu en-aut-sei=Fujiwara en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwaoChikako en-aut-sei=Iwao en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitagawaHiroshi en-aut-sei=Kitagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshinoIchiro en-aut-sei=Yoshino en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GemmaAkihiko en-aut-sei=Gemma en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MitsudomiTetsuya en-aut-sei=Mitsudomi en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SaitoYoshinobu en-aut-sei=Saito en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= affil-num=2 en-affil=Division of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Oncology Medical, AstraZeneca K.K kn-affil= affil-num=5 en-affil=Oncology Medical, AstraZeneca K.K kn-affil= affil-num=6 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K kn-affil= affil-num=7 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K kn-affil= affil-num=8 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K kn-affil= affil-num=9 en-affil=Oncology Medical, AstraZeneca K.K kn-affil= affil-num=10 en-affil=Oncology Medical, AstraZeneca K.K kn-affil= affil-num=11 en-affil=Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital kn-affil= affil-num=12 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=13 en-affil=Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Pulmonary Medicine, Nippon Medical School Musashi Kosugi Hospital kn-affil= en-keyword=carcinoma kn-keyword=carcinoma en-keyword=chemoradiotherapy kn-keyword=chemoradiotherapy en-keyword=durvalumab kn-keyword=durvalumab en-keyword=interstitial kn-keyword=interstitial en-keyword=lung diseases kn-keyword=lung diseases en-keyword=non-small- cell lung kn-keyword=non-small- cell lung END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=1 article-no= start-page=160 end-page=173 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-Term Safety and Effectiveness of Durvalumab in Unresectable Stage III NSCLC in Japan: A Multicenter Prospective Study (AYAME) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Based on the PACIFIC trial results, durvalumab after chemoradiotherapy (CRT) is the standard of care for unresectable stage III NSCLC. However, few large-scale studies have prospectively evaluated its long-term effectiveness and safety, including subsequent treatment.
Methods: This multicenter, noninterventional study (AYAME) enrolled patients who were prescribed durvalumab for unresectable stage III NSCLC after CRT (July 2019?December 2020; 52 sites; Japan). Patients received durvalumab for a maximum of 12 months and were prospectively followed up for 3 years, including the post-durvalumab treatment period. Primary end points were real-world progression-free survival (rwPFS), the incidence of interstitial lung disease (ILD), and adverse events of special interest (AESIs).
Results: Of the 529 enrolled patients, 512 received durvalumab and 511 comprised the safety analysis population. The median time to onset of the first presentation or occurrence of ILD was 45.0 days. ILD of any grade occurred in 387 patients (75.7%) over the 3-year study period: grade 3, 57 (11.2%); grade 4, none (0.0%); and grade 5, 9 (1.8%). The most common AESIs of any grade during durvalumab treatment were thyroid dysfunction (12.5%), hepatic dysfunction (7.2%), and colitis (2.0%). No durvalumab treatment-related ILD or AESIs occurred during the post-treatment period. The median [95% confidence interval] rwPFS was 23.2 [18.2, 27.2] months in the effectiveness analysis population (n = 495). rwPFS rates were 62.5%, 54.6%, 49.4%, and 40.4% at 12, 18, 24, and 36 months, respectively.
Conclusions: This first and largest prospective, observational study demonstrated the long-term safety and effectiveness of durvalumab for unresectable stage III NSCLC after CRT in a real-world clinical setting.
Clinical Trial Registration: UMIN000037090 and NCT03995875 en-copyright= kn-copyright= en-aut-name=KenmotsuHirotsugu en-aut-sei=Kenmotsu en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaitoYoshinobu en-aut-sei=Saito en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UematsuShinya en-aut-sei=Uematsu en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkdemirBurak en-aut-sei=Akdemir en-aut-mei=Burak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuiAyako en-aut-sei=Fukui en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KotoRyo en-aut-sei=Koto en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiwaraMasakazu en-aut-sei=Fujiwara en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwaoChikako en-aut-sei=Iwao en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitagawaHiroshi en-aut-sei=Kitagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshinoIchiro en-aut-sei=Yoshino en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GemmaAkihiko en-aut-sei=Gemma en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MitsudomiTetsuya en-aut-sei=Mitsudomi en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamamotoNobuyuki en-aut-sei=Yamamoto en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Division of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Nippon Medical School, Musashi Kosugi Hospital kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Oncology Medical, AstraZeneca K.K. kn-affil= affil-num=5 en-affil=Oncology Medical, AstraZeneca K.K. kn-affil= affil-num=6 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K. kn-affil= affil-num=7 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K. kn-affil= affil-num=8 en-affil=Evidence and Observational Research, Medical, AstraZeneca K.K. kn-affil= affil-num=9 en-affil=Oncology Medical, AstraZeneca K.K. kn-affil= affil-num=10 en-affil=Oncology Medical, AstraZeneca K.K. kn-affil= affil-num=11 en-affil=Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital kn-affil= affil-num=12 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=13 en-affil=Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine and Faculty of Medicine & Hospital kn-affil= affil-num=14 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= en-keyword=Durvalumab kn-keyword=Durvalumab en-keyword=Chemoradiotherapy kn-keyword=Chemoradiotherapy en-keyword=Interstitial lung disease kn-keyword=Interstitial lung disease en-keyword=Real-world evidence kn-keyword=Real-world evidence en-keyword=Unresectable stage III NSCLC kn-keyword=Unresectable stage III NSCLC END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=5 article-no= start-page=e84709 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250523 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phase II Study of Platinum Re-administration in Non-small Cell Lung Cancer Following Chemoimmunotherapy Resistance en-subtitle= kn-subtitle= en-abstract= kn-abstract=Platinum compounds represent standard treatments for various cancers. However, the efficacy of re-administrating platinum compounds has been demonstrated only in ovarian cancer and small cell lung cancer (SCLC), with its utility in non-small cell lung cancer (NSCLC) remaining unclear. Given that the prognosis of NSCLC has improved with effective treatments such as immune checkpoint inhibitors (ICIs), we propose a multicenter, single-arm, prospective phase II trial of re-administrating platinum-based combination therapy for NSCLC. Patients with NSCLC who have progressed after chemoimmunotherapy and exhibit a platinum-free interval of 85 days or more will receive carboplatin combination therapy. The drugs combined with carboplatin - pemetrexed, nab-paclitaxel, or gemcitabine - must not have been administered previously. The primary endpoint is progression-free survival (PFS), assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Assuming a threshold PFS of 4.2 months and an expected hazard ratio of 0.60, the required sample size is calculated as 40 patients to achieve 70% power with a 5% alpha error. Secondary endpoints included objective response rate, toxicity, and overall survival. This study will clarify the efficacy of re-administrating platinum compounds to patients with NSCLC who have developed resistance to chemoimmunotherapy. en-copyright= kn-copyright= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HosokawaShinobu en-aut-sei=Hosokawa en-aut-mei=Shinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokoyamaToshihide en-aut-sei=Yokoyama en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugimotoKeisuke en-aut-sei=Sugimoto en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KudoKenichiro en-aut-sei=Kudo en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkadaToshiaki en-aut-sei=Okada en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaedaTadashi en-aut-sei=Maeda en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawaiHaruyuki en-aut-sei=Kawai en-aut-mei=Haruyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasugiMasayuki en-aut-sei=Yasugi en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=InoueKoji en-aut-sei=Inoue en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NinomiyaTakashi en-aut-sei=Ninomiya en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OzeIsao en-aut-sei=Oze en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=3 en-affil=Respiratory Medicine, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=5 en-affil=Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= affil-num=6 en-affil=Respiratory Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=7 en-affil=Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=8 en-affil=Respiratory Medicine, National Hospital Organization Yamaguchi Ube Medical Center kn-affil= affil-num=9 en-affil=Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=10 en-affil=Respiratory Medicine, Chugoku Central Hospital kn-affil= affil-num=11 en-affil=Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=12 en-affil=Respiratory Medicine, Iwakuni Medical Center kn-affil= affil-num=13 en-affil=Respiratory Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=14 en-affil=Division of Molecular Medicine, Aichi Cancer Center Research Institute kn-affil= affil-num=15 en-affil=Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= en-keyword=carboplatin kn-keyword=carboplatin en-keyword=clinical trial kn-keyword=clinical trial en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=platinum-free interval kn-keyword=platinum-free interval en-keyword=re-administration kn-keyword=re-administration END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=2 article-no= start-page=e79601 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Elevated Plasma Progastrin-Releasing Peptide Levels Associated With the Diagnosis of Pulmonary Carcinoid Tumors: A Report of Two Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary carcinoids are the type of thoracic malignant tumors classified as neuroendocrine tumors. Case 1 involved a 59-year-old woman with a nodular shadow in the left upper pulmonary field observed on chest radiography. Chest computed tomography (CT) scan revealed a nodule in the left upper lobe and a soft tissue tumor near the left third rib. Given her elevated plasma progastrin-releasing peptide (ProGRP) level, a CT-guided biopsy was performed, confirming a diagnosis of pulmonary carcinoid with solitary bone metastasis. She subsequently underwent partial resection of the left upper lobe and the rib tumor. Case 2 involved a 67-year-old woman referred to our hospital after a chest CT scan revealed a nodule in the left lingular region. Her plasma ProGRP level was elevated, and a CT-guided biopsy confirmed a diagnosis of pulmonary carcinoid. As no lymph node metastases were detected, she underwent segmental resection of the left upper lobe. In both cases, plasma ProGRP levels decreased following surgical resection. These findings suggest that plasma ProGRP levels may serve as a useful diagnostic marker for pulmonary carcinoids. en-copyright= kn-copyright= en-aut-name=YamaokaTakashi en-aut-sei=Yamaoka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NoumiTaku en-aut-sei=Noumi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoChiaki en-aut-sei=Matsumoto en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugimotoKeisuke en-aut-sei=Sugimoto en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= en-keyword=biopsy kn-keyword=biopsy en-keyword=case report kn-keyword=case report en-keyword=progrp kn-keyword=progrp en-keyword=pulmonary carcinoid kn-keyword=pulmonary carcinoid en-keyword=tumor marker kn-keyword=tumor marker END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260913 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical Significance of a Cell-Of-Origin-Based Classification in Pancreatic Ductal Adenocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with limited therapeutic options and poor clinical outcomes. Although PDAC has traditionally been thought to arise from ductal epithelial cells, recent studies using genetically engineered mouse models have demonstrated that acinar cells can also serve as a cell of origin, giving rise to tumors with distinct biological properties. Here, we investigated whether such lineage-specific differences are preserved in human PDAC. RNA sequencing was performed on resected specimens from 40 treatment-na?ve patients with PDAC, and tumors were classified into Acinar- and Ductal-subtypes using lineage-specific gene expression signatures derived from mouse models. This classification strategy was further applied to human PDAC cell lines, followed by in vitro drug sensitivity assays. Patients with Acinar-subtype tumors had significantly longer overall survival than those with Ductal-subtype tumors (median, 54.0 vs. 26.5?months; p? Methods: We retrospectively analyzed 225 nonagenarians undergoing surgical resection of CRC at 15 institutions between 2011 and 2022. Patients were stratified by GNRI-high/low status using two cutoffs: 98 (Cohort 1) and 86 (Cohort 2). Outcomes included postoperative complications, length of hospital stay, and overall survival (OS). Stabilized inverse-probability-of-treatment weighting (IPTW) was used to adjust for measured confounding.
Results: The median age was 92?years (female, 64.9%; colon cancer, 79.6%). GNRI-high patients had higher body mass index and albumin levels. Complication rates did not differ between the groups. After adjustment, GNRI-high patients in Cohort 1 had a shorter expected hospital stay (ratio 0.70, 95% CI 0.51?0.96; p?=?0.025) but no significant OS difference. In Cohort 2, GNRI-high patients had better OS (p? Conclusions: Preoperative GNRI was associated with hospital stay and OS in nonagenarians undergoing CRC surgery, although the OS association was significant only with the cohort-derived cutoff of 86, which requires external validation, and not with the literature-based cutoff of 98. The GNRI is a simple tool to stratify surgical risk and optimize perioperative nutritional status in this vulnerable population. en-copyright= kn-copyright= en-aut-name=ToshimaToshiaki en-aut-sei=Toshima en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakanagaSatoe en-aut-sei=Takanaga en-aut-mei=Satoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InadaRyo en-aut-sei=Inada en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhtaniTsuyoshi en-aut-sei=Ohtani en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaRyosuke en-aut-sei=Yoshida en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HoriNaoto en-aut-sei=Hori en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShigemitsuKaoru en-aut-sei=Shigemitsu en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoSumiharu en-aut-sei=Yamamoto en-aut-mei=Sumiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KubotaTetsushi en-aut-sei=Kubota en-aut-mei=Tetsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkanoYuka en-aut-sei=Okano en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NobuhisaTetsuji en-aut-sei=Nobuhisa en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaniguchiFumitaka en-aut-sei=Taniguchi en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IshikawaWataru en-aut-sei=Ishikawa en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsudaTatsuo en-aut-sei=Matsuda en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UmeokaTatsuo en-aut-sei=Umeoka en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=The Setouchi Colorectal Neoplasm Registration Study Group en-aut-sei=The Setouchi Colorectal Neoplasm Registration Study Group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Surgery, Kagawa Rosai Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Medical Development Field, Okayama University kn-affil= affil-num=5 en-affil=Department of Surgery, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Surgery, Saiseikai Okayama Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Okayama Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, Tottori Municipal Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, Tsuyama Chuo Hospital kn-affil= affil-num=10 en-affil=Department of Surgery, Okayama City Hospital kn-affil= affil-num=11 en-affil=Department of Surgery, Kobe Red Cross Hospital kn-affil= affil-num=12 en-affil=Department of Surgery, Onomichi City Hospital kn-affil= affil-num=13 en-affil=Department of Surgery, Himeji Red Cross Hospital kn-affil= affil-num=14 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=15 en-affil=Department of Surgery, Fukuyama City Hospital kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Surgery, Matsuda Hospital kn-affil= affil-num=18 en-affil=Department of Surgery, Matsuyama City Hospital kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=20 en-affil= kn-affil= en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=geriatric nutritional risk index kn-keyword=geriatric nutritional risk index en-keyword=oldest-old patients kn-keyword=oldest-old patients en-keyword=overall survival kn-keyword=overall survival en-keyword=surgical outcome kn-keyword=surgical outcome END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260929 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Natural Variation in Brachypodium distachyon Primarily Links Lignin Reinforcement to Rhizoctonia solani Resistance en-subtitle= kn-subtitle= en-abstract= kn-abstract= 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=WatanabeMegumi en-aut-sei=Watanabe en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakataNanami en-aut-sei=Sakata en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuiHidenori en-aut-sei=Matsui en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ToyodaKazuhiro en-aut-sei=Toyoda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IchinoseYuki en-aut-sei=Ichinose en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NoutoshiYoshiteru en-aut-sei=Noutoshi en-aut-mei=Yoshiteru 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=Tea Research Institute of Sri Lanka 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= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=2 article-no= start-page=143 end-page=151 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240916 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cranial and spinal computed tomography (CT) angiography with photon-counting detector CT: comparison with angiographic and operative findings en-subtitle= kn-subtitle= en-abstract= kn-abstract=The clinical imaging features of photon-counting detector (PCD) computed tomography (CT) are mainly known as dose reduction, improvement of spatial resolution, and reduction of artifacts compared to energy-integrating detector CT (EID-CT). The utility of cranial and spinal PCD-CT and PCD-CT angiography (CTA) has been previously reported. CTA is a widely used technique for noninvasive evaluation. Cranial CTA is important in brain tumors, especially glioblastoma; it evaluates whether the tumor is highly vascularized prior to an operation and helps in the diagnosis and assessment of bleeding risk. Spinal CTA has an important role in the estimation of feeders and drainers prior to selective angiography in the cases of spinal epidural arteriovenous fistulas and spinal tumors, especially in hemangioblastoma. So far, EID-CTA is commonly performed in an adjunctive role prior to selective angiography; PCD-CTA with high spatial resolution can be an alternative to selective angiography. In the cases of cerebral aneurysms, flow diverters are important tools for the treatment of intracranial aneurysms, and postoperative evaluation with cone beam CT with angiography using diluted contrast media is performed to evaluate stent adhesion and in-stent thrombosis. If CTA can replace selective angiography, it will be less invasive for the patient. In this review, we present representative cases with PCD-CT. We also show how well the cranial and spinal PCD-CTA approaches the accuracy of angiographic and intraoperative findings. en-copyright= kn-copyright= en-aut-name=HigakiFumiyo en-aut-sei=Higaki en-aut-mei=Fumiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiramatsuMasafumi en-aut-sei=Hiramatsu en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasadaSusumu en-aut-sei=Sasada en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HarumaJun en-aut-sei=Haruma en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=InoueTomohiro en-aut-sei=Inoue en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorimitsuYusuke en-aut-sei=Morimitsu en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AkagiNoriaki en-aut-sei=Akagi en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuiYusuke en-aut-sei=Matsui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Radiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Radiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Photon-counting detector CT kn-keyword=Photon-counting detector CT en-keyword=Energy-integrating detector CT kn-keyword=Energy-integrating detector CT en-keyword=CT angiography kn-keyword=CT angiography en-keyword=Neuroimaging kn-keyword=Neuroimaging en-keyword=Spine kn-keyword=Spine END start-ver=1.4 cd-journal=joma no-vol=94 cd-vols= no-issue=1 article-no= start-page=1 end-page=18 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250311 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An XAI-based meta-parameter tuning for time-series forecasting en-subtitle= kn-subtitle= en-abstract= kn-abstract=How can we efficiently determine meta-parameter values for deep learning-based time-series forecasting given a time-series dataset? This paper introduces Xtune, an efficient and novel meta-parameter tuning method for deep learning-based time-series forecasting, leveraging explainable AI techniques. In particular, this study focuses on optimizing the window size for time-series forecasting. Xtune determines the optimal meta-parameter value for these methods and can also be applied to tune the window size for anomaly detection methods that utilize deep learning-based time-series forecasting. Extensive experiments on real-world datasets and forecasting methods demonstrate that Xtune efficiently identifies the optimal meta-parameter value and consistently outperforms the existing methods in terms of execution speed. en-copyright= kn-copyright= en-aut-name=NakagawaHiroyuki en-aut-sei=Nakagawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SumitaShimon en-aut-sei=Sumita en-aut-mei=Shimon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IidaRyuichi en-aut-sei=Iida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuchiyaTatsuhiro en-aut-sei=Tsuchiya en-aut-mei=Tatsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Osaka University kn-affil= affil-num=3 en-affil=Okayama University kn-affil= affil-num=4 en-affil=Osaka University kn-affil= en-keyword=Parameter optimization kn-keyword=Parameter optimization en-keyword=XAI kn-keyword=XAI en-keyword=Deep learning kn-keyword=Deep learning en-keyword=Time-series forecasting kn-keyword=Time-series forecasting en-keyword=Anomaly detection kn-keyword=Anomaly detection END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=3 article-no= start-page=76 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel combination therapy for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma: a systematic review and network meta-analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent phase 3 randomized controlled trials (RCTs) demonstrate the promising impact of immune checkpoint inhibitor (ICI)-based combination therapies on locally advanced or metastatic urothelial carcinoma (UC). However, comparative data on the efficacy and toxicity of different ICI-based combinations are lacking. This study aims to compare the efficacy of first-line ICI-based combination therapies for locally advanced or metastatic UC using phase 3 RCT data. In November 2023, three databases were searched for RCTs evaluating oncological outcomes in patients with locally advanced or metastatic UC who were treated with first-line ICI-based combination therapies. Network meta-analysis (NMA) was conducted to compare outcomes, including overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), and treatment-related adverse events (TRAEs). Subgroup analyses were based on PD-L1 status and cisplatin eligibility. The NMA included five RCTs. Enfortumab vedotin (EV) + pembrolizumab ranked the highest for improving OS (100%), PFS (100%), ORR (96%), and CRR (96%), followed by nivolumab + chemotherapy. EV + pembrolizumab combination superiority held across PD-L1 status and cisplatin eligibility. In patients who are cisplatin-eligible, EV + pembrolizumab significantly improved OS (HR: 0.68, 95%CI 0.47?0.99) and PFS (HR: 0.67, 95%CI 0.49?0.92) compared to nivolumab + chemotherapy. Durvalumab + tremelimumab was the safest combination for severe TRAEs, and EV + pembrolizumab ranked second. Our analyses support EV + pembrolizumab combination as a first-line treatment for locally advanced or metastatic UC. Thus, EV + pembrolizumab may become a guideline-changing standard treatment. en-copyright= kn-copyright= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LaukhtinaEkaterina en-aut-sei=Laukhtina en-aut-mei=Ekaterina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=RajwaPawel en-aut-sei=Rajwa en-aut-mei=Pawel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=QuhalFahad en-aut-sei=Quhal en-aut-mei=Fahad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=PradereBenjamin en-aut-sei=Pradere en-aut-mei=Benjamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukuokayaWataru en-aut-sei=Fukuokaya en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwataniKosuke en-aut-sei=Iwatani en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=PichlerRenate en-aut-sei=Pichler en-aut-mei=Renate kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TeohJeremy Yuen-Chun en-aut-sei=Teoh en-aut-mei=Jeremy Yuen-Chun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MoschiniMarco en-aut-sei=Moschini en-aut-mei=Marco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KrajewskiWojciech en-aut-sei=Krajewski en-aut-mei=Wojciech kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MikiJun en-aut-sei=Miki en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ShariatShahrokh F. en-aut-sei=Shariat en-aut-mei=Shahrokh F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KimuraTakahiro en-aut-sei=Kimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=European Association of Urology?Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU) en-aut-sei=European Association of Urology?Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU) en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=2 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=3 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=7 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=8 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=9 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=10 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=11 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck kn-affil= affil-num=13 en-affil=S.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong kn-affil= affil-num=14 en-affil=Department of Urology, San Raffaele Hospital and Scientific Institute kn-affil= affil-num=15 en-affil=Department of Minimally Invasive and Robotic Urology, Wroc?aw Medical University kn-affil= affil-num=16 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=17 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=18 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=19 en-affil= kn-affil= en-keyword=Chemotherapy kn-keyword=Chemotherapy en-keyword=Enfortumab vedotin kn-keyword=Enfortumab vedotin en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors en-keyword=Metastasis kn-keyword=Metastasis en-keyword=Urothelial carcinoma kn-keyword=Urothelial carcinoma END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=30 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relationship Between Heated Tobacco Products and Placental Abruption: A Prospective Cohort Study Using Online Questionnaire en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Placental abruption (PA) is a critical obstetric complication, with maternal smoking recognized as a key risk factor. Despite the increased use of heated tobacco products (HTPs), the impact of HTPs remains unclear. This study investigated whether pregnant women using HTPs are at a higher risk of PA than non-users.
Methods: We analyzed data from gthe Japan COVID-19 and Society Internet Survey,h a prospective, self-reported online survey cohort. Questionnaires were randomly distributed between July 28, 2021, and August 30, 2021. Pregnant respondents in 2021 were invited to complete an additional survey from February 14, 2022, to February 28, 2022. We set the outcome as the absolute risk difference (aRD) and relative risk ratio (rRR) of PA incidence due to smoking HTPs in the first trimester of pregnancy. The sample size included 12 836 participants. We calculated outcomes using a generalized linear model (GLM) and inverse probability of treatment weighting (IPTW). We also performed a Bayesian approach and multiple-bias analysis for sensitivity analysis.
Results: We found the robust aRD of 0.07 (95% confidence interval (CI): 0.06, 0.09) and the rRR of 11.3 (95% CI: 7.5, 17.0). Multiple bias analyses showed that unmeasurable confounders would need to have at least an rRR?=?14 relationship with both exposure and outcome to disprove the observed association. There has not been post hoc analysis or secondary use of data.
Conclusion: Early pregnancy use of HTPs is associated with an increased risk of PA. en-copyright= kn-copyright= en-aut-name=OobaHikaru en-aut-sei=Ooba en-aut-mei=Hikaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MakiJota en-aut-sei=Maki en-aut-mei=Jota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TabuchiTakahiro en-aut-sei=Tabuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Division of Epidemiology, School of Public Health, Tohoku University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Placental abruption kn-keyword=Placental abruption en-keyword=Heated tobacco products kn-keyword=Heated tobacco products en-keyword=Pregnancy kn-keyword=Pregnancy en-keyword=Tobacco use kn-keyword=Tobacco use END start-ver=1.4 cd-journal=joma no-vol=980 cd-vols= no-issue=1 article-no= start-page=117 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250207 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Observing Supernova Neutrino Light Curves with Super-Kamiokande. V. Distance Estimation with Neutrinos en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neutrinos are pivotal signals in multimessenger observations of supernovae (SNe). Recent advancements in the analysis method of supernova (SN) neutrinos, especially in quantitative analysis, have significantly broadened scientific possibilities. This study demonstrates the feasibility of estimating distances to SNe using neutrinos. This estimation utilizes the direct relationship between the radius of a neutron star (NS) and the distance to the supernova, which is analogous to main-sequence fitting. The radius of an NS is determined with an approximate uncertainty of 10% through observations such as X-rays and gravitational waves. By integrating this information, the distance to the supernova can be estimated with an uncertainty of within 15% at a 95% confidence level. It has been established that neutrinos can pinpoint the direction of supernovae, and when combined with distance estimates, three-dimensional localization becomes achievable. This capability is vital for follow-up observations using multimessenger approaches. Moreover, more precise distance determinations to SNe through follow-up observations, such as optical observations, allow for accurate measurements of neutron-star radii. This data, via the neutron-star mass?radius relationship, could provide various insights into nuclear physics. en-copyright= kn-copyright= en-aut-name=SuwaYudai en-aut-sei=Suwa en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaradaAkira en-aut-sei=Harada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriMasamitsu en-aut-sei=Mori en-aut-mei=Masamitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakazatoKenfichiro en-aut-sei=Nakazato en-aut-mei=Kenfichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkahoRyuichiro en-aut-sei=Akaho en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaradaMasayuki en-aut-sei=Harada en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KoshioYusuke en-aut-sei=Koshio en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanishiFumi en-aut-sei=Nakanishi en-aut-mei=Fumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SumiyoshiKohsuke en-aut-sei=Sumiyoshi en-aut-mei=Kohsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WendellRoger A. en-aut-sei=Wendell en-aut-mei=Roger A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Earth Science and Astronomy, The University of Tokyo kn-affil= affil-num=2 en-affil=Interdisciplinary Theoretical and Mathematical Sciences Program (iTHEMS), RIKEN kn-affil= affil-num=3 en-affil=Division of Science, National Astronomical Observatory of Japan kn-affil= affil-num=4 en-affil=Faculty of Arts and Science, Kyushu University kn-affil= affil-num=5 en-affil=Faculty of Science and Engineering, Waseda University kn-affil= affil-num=6 en-affil=Department of Physics, Okayama University kn-affil= affil-num=7 en-affil=Department of Physics, Okayama University kn-affil= affil-num=8 en-affil=Department of Physics, Okayama University kn-affil= affil-num=9 en-affil=National Institute of Technology, Numazu College kn-affil= affil-num=10 en-affil=Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU, WPI), Todai Institutes for Advanced Study, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue= article-no= start-page=1 end-page=16 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical impact of hypomagnesemia induced by necitumumab plus cisplatin and gemcitabine treatment in patients with advanced lung squamous cell carcinoma: a subanalysis of the NINJA study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The clinical impact of hypomagnesemia induced by necitumumab plus gemcitabine and cisplatin (GCN) as a second-line or later therapy is unclear.
Objective: We aimed to evaluate the clinical characteristics and survival impact of hypomagnesemia induced by this therapy.
Design: This was a sub-analysis of the retrospective multicenter NINJA study.
Methods: Among the 93 patients enrolled in the NINJA study, this subanalysis included 75 patients with baseline serum magnesium concentrations.
Results: The incidence of grade ?2 hypomagnesemia was 18.0% in the patients with normal baseline serum magnesium concentrations and 42.8% in those with low concentrations (p?=?0.073). The discontinuation rates of GCN treatment owing to hypomagnesemia in each group were 0% and 7.1%, respectively (p?=?0.187). The number of necitumumab doses and severity of hypomagnesemia were positively correlated (r?=?0.389, p? Conclusion: GCN as a second-line or later therapy may be tolerable regardless of the patientfs 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 Citizenfs 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=2 cd-vols= no-issue=3 article-no= start-page=45 end-page=56 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241130 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relationship between food security and dietary habits and subjective sense of health and subjective sense of well-being among residents of large-scale housing complexes in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: This study aimed to determine the relationship between food security and dietary habits and subjective health and subjective well-being among residents of a large-scale housing complex in Japan. Methods: This study used a cross-sectional design through a self-administered questionnaire survey. The study subjects were residents of Mukogawa Danchi in Nishinomiya City, Hyogo Prefecture, Japan, and data from 515 households out of 6,857 total dwelling units were used for the analysis. Food security status (HFSSM), dietary diversity score (HDDS), diet, eating behavior, subjective sense of health, and subjective sense of well-being were examined using logistic regression analysis. Results: Food insecurity was negatively associated with household dietary diversity scores (OR [95%CI]:0.49 [0.24?0.98] p = 0.044). Similarly, food insecurity was negatively associated with having a nutritionally balanced diet and having a satisfactory amount of food. There was also a negative association with family meals. There was a negative association between food insecurity and a subjective sense of health and a negative association (0.35 [0.15?0.78] p = 0.011) with a subjective sense of well-being among those aged 65 and older. Conclusions: In a large-scale housing complex in Japan, inadequate dietary intake was observed in food-insecure households; they ate meals less frequently with their families. Additionally, residents experiencing food insecurity tended to have lower subjective health and subjective well-being, depending on their age. en-copyright= kn-copyright= en-aut-name=WakimotoKeiko en-aut-sei=Wakimoto en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Yokoro-HisanariMiyuki en-aut-sei=Yokoro-Hisanari en-aut-mei=Miyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhtsuboAkira en-aut-sei=Ohtsubo en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiTatsuya en-aut-sei=Fujii en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoJotaro en-aut-sei=Kato en-aut-mei=Jotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OgasawaraHitoshi en-aut-sei=Ogasawara en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KudoDaisuke en-aut-sei=Kudo en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FukuiMinae en-aut-sei=Fukui en-aut-mei=Minae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujitaYuichi en-aut-sei=Fujita en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=School of Food Sciences and Nutrition, Mukogawa Womenfs University kn-affil= affil-num=2 en-affil=Faculty of Education, Okayama University kn-affil= affil-num=3 en-affil=Community Liaison Division for Education and Research, Mukogawa Womenfs University kn-affil= affil-num=4 en-affil=School of Education, Mukogawa Womenfs University kn-affil= affil-num=5 en-affil=School of Letters, Mukogawa Womenfs University kn-affil= affil-num=6 en-affil=School of Nursing, Mukogawa Womenfs University kn-affil= affil-num=7 en-affil=School of Nursing Science, Meiji University of Integrative Medicine kn-affil= affil-num=8 en-affil=Ichikan Nursing Development center for Diversity, Kobe City College of Nursing kn-affil= affil-num=9 en-affil=School of Nursing, Mukogawa Womenfs University kn-affil= en-keyword=food security kn-keyword=food security en-keyword=dietary quality kn-keyword=dietary quality en-keyword=eating behavior kn-keyword=eating behavior en-keyword=self-rated health kn-keyword=self-rated health END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=1 article-no= start-page=5 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250213 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association Between Alcohol Use Patterns and Insomnia Symptoms or Poor Sleep Quality Among Adult Women: An Internet Cross-Sectional Survey in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=It is unclear whether patterns of alcohol consumption are associated with sleep disturbance. We aimed to investigate the relationship between comprehensive alcohol-related factors and insomnia symptoms, as well as sleep quality, among adult women in Japan. Responses to an online cross-sectional survey were gathered from 12,000 women. The survey items included demographic characteristics, alcohol consumption (Alcohol Use Disorders Identification Test, nightcaps, years of drinking), sleep-related factors (sleep duration, insomnia symptoms, sleep quality), lifestyle-related factors, and mental health. Binary logistic regression was used to investigate the relationship between alcohol consumption and both insomnia symptoms and sleep quality. A total of 10,233 women were included in the final analysis. The results revealed that several alcohol-related behaviors, including the consumption of nightcaps and years of drinking, were significantly associated with insomnia symptoms and poor sleep quality. Specifically, nightcaps were significantly associated with all types of insomnia symptoms and poor sleep quality, with a higher odds ratio than other alcohol-related items. Our findings suggest that specific alcohol-related behaviors, particularly the consumption of nightcaps, are associated with insomnia symptoms and poor sleep quality among women. Intervention programs for alcohol consumption should be provided to prevent sleep problems among women. en-copyright= kn-copyright= en-aut-name=NakajimaSuguru en-aut-sei=Nakajima en-aut-mei=Suguru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtsukaYuichiro en-aut-sei=Otsuka en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KaneitaYoshitaka en-aut-sei=Kaneita en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItaniOsamu en-aut-sei=Itani en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KuwabaraYuki en-aut-sei=Kuwabara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KinjoAya en-aut-sei=Kinjo en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MinobeRuriko en-aut-sei=Minobe en-aut-mei=Ruriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaesatoHitoshi en-aut-sei=Maesato en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiguchiSusumu en-aut-sei=Higuchi en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KandaHideyuki en-aut-sei=Kanda en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshimotoHisashi en-aut-sei=Yoshimoto en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=JikeMaki en-aut-sei=Jike en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KasugaHideaki en-aut-sei=Kasuga en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ItoTeruna en-aut-sei=Ito en-aut-mei=Teruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OsakiYoneatsu en-aut-sei=Osaki en-aut-mei=Yoneatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=2 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=3 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=4 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=5 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=6 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=7 en-affil=National Hospital Organization Kurihama Medical and Addiction Center kn-affil= affil-num=8 en-affil=National Hospital Organization, Ryukyu Hospital kn-affil= affil-num=9 en-affil=National Hospital Organization Kurihama Medical and Addiction Center kn-affil= affil-num=10 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Family Medicine, General Practice and Community Health, Faculty of Medicine, University of Tsukuba kn-affil= affil-num=12 en-affil=Department of Food Science and Nutrition, Faculty of Life and Environmental Science, Showa Womenfs University kn-affil= affil-num=13 en-affil=Department of Hygiene and Preventive Medicine, Fukushima Medical University kn-affil= affil-num=14 en-affil=Department of Food and Nutrition, Koriyama Womenfs University kn-affil= affil-num=15 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= en-keyword=alcohol drinking kn-keyword=alcohol drinking en-keyword=female kn-keyword=female en-keyword=sleep duration kn-keyword=sleep duration en-keyword=sleep quality kn-keyword=sleep quality END start-ver=1.4 cd-journal=joma no-vol=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 patientfs 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 Citizenfs 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=35 cd-vols= no-issue=10 article-no= start-page=e70808 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260923 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Conformational stability and domain]specific structural features of tumor autoantigens regulate autoantibody epitope propensity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Autoantibodies against tumor-associated autoantigens are clinically valuable biomarkers for cancer diagnosis; however, the structural determinants governing epitope selectivity remain unknown. Here, we investigated whether the intrinsic conformational stability of target autoantigens regulates the epitope propensity of tumor-associated autoantibodies in non-small cell lung cancer. Using a dual-antigen Luminex bead-based assay that presents each autoantigen in both native and S-cationized denatured forms, we directly compared IgG autoantibody reactivity toward conformational and linear epitopes across 11 autoantigens. Intrinsically disordered aggregation-prone autoantigens, including cancer/testis antigens, NY-ESO-1, and XAGE-1b, predominantly elicit linear epitope-directed responses, whereas thermodynamically stable soluble autoantigens generally drive conformational epitope recognition. Intriguingly, for autoantigens harboring both ordered and disordered segments, the immune response is strictly guided by domain-specific biophysics: while p53-specific antibodies preferentially target their flanking disordered regions, the Wilms' tumor protein 1 exceptionally drives conformational recognition directed toward its structured zinc-finger domains. Recombinant solubility in Escherichia coli broadly correlated with epitope class across all 11 autoantigens, confirming that prokaryotic folding efficiency generally reflects intrinsic conformational stability in vivo for autonomously folding monomeric cytosolic proteins. Independent computational validation was provided by the concordance between the experimental solubility ratios and AlphaFold3-derived Rosetta energy unit/solvent-accessible surface area values, demonstrating the convergence of thermodynamic estimates and patient-derived immune data within a unifying biophysical framework. These findings establish that the autoantibody epitope propensity is closely associated with the thermodynamic stability of the target autoantigen and provide a rational basis for tailoring antigen preparation strategies for autoantibody-based cancer diagnosis. en-copyright= kn-copyright= en-aut-name=MiyamotoAi en-aut-sei=Miyamoto en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoRika en-aut-sei=Yamamoto en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakaguchiRyui en-aut-sei=Sakaguchi en-aut-mei=Ryui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KutsumaRikako en-aut-sei=Kutsuma en-aut-mei=Rikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriTakeru en-aut-sei=Mori en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MasuiMirei en-aut-sei=Masui en-aut-mei=Mirei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HonjoTomoko en-aut-sei=Honjo en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FutamiMidori en-aut-sei=Futami en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoriiMariko en-aut-sei=Morii en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeHiromi en-aut-sei=Watanabe en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FutamiJunichiro en-aut-sei=Futami en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Department of Bioscience, Faculty of Life Science, Okayama University of Science kn-affil= affil-num=9 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=autoantibody kn-keyword=autoantibody en-keyword=biomarker kn-keyword=biomarker en-keyword=cancer/testis antigen kn-keyword=cancer/testis antigen en-keyword=epitope propensity kn-keyword=epitope propensity en-keyword=intrinsically disordered regions kn-keyword=intrinsically disordered regions en-keyword=protein engineering kn-keyword=protein engineering en-keyword=tumor-associated antigens kn-keyword=tumor-associated antigens END start-ver=1.4 cd-journal=joma no-vol=53 cd-vols= no-issue=18 article-no= start-page=e2026GL123823 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260926 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hydrogen-Bond Symmetrization in Hydrous Aluminous Silica Enhances Deep-Mantle Water Cycle en-subtitle= kn-subtitle= en-abstract= kn-abstract=(Al, H)-bearing CaCl2-type SiO2 serves as a key water carrier in Earth's deep-water cycle. Evolution of hydrogen-bond symmetrization in this phase was measured up to 62 GPa and 800 K by synchrotron infrared and Raman spectroscopy, and X-ray diffraction. It undergoes symmetrization at ?30 GPa and 300 K, while elevated temperature to 800 K lowers the onset pressure to ?12 GPa. This implies that the symmetrized phase will form directly near the base of the transition zone in (Al, H)-rich subducted slabs, and deeper in (Al, H)-poor slabs via transformation from stishovite. More importantly, this symmetrization state stiffens the crystal lattice and immobilizes hydrogen within the structure, enhancing water retention and preventing hydrogen loss during subduction to the lower mantle. Our findings suggest that this phase acts as an important deep-water reservoir capable of transporting water to the lower mantle, thereby linking the deep-water cycle from Earth's surface to core-mantle boundary. en-copyright= kn-copyright= en-aut-name=ZhaoChaoshuai en-aut-sei=Zhao en-aut-mei=Chaoshuai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaoZhu en-aut-sei=Mao en-aut-mei=Zhu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YuYingxin en-aut-sei=Yu en-aut-mei=Yingxin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SunNingyu en-aut-sei=Sun en-aut-mei=Ningyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FuYunhua en-aut-sei=Fu en-aut-mei=Yunhua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZhangJianbo en-aut-sei=Zhang en-aut-mei=Jianbo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LiermannHanns]Peter en-aut-sei=Liermann en-aut-mei=Hanns]Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= affil-num=1 en-affil=State Key Laboratory of Precision Geodesy, University of Science and Technology of China kn-affil= affil-num=2 en-affil=State Key Laboratory of Precision Geodesy, University of Science and Technology of China kn-affil= affil-num=3 en-affil=Department of Earth Sciences, University of Oxford kn-affil= affil-num=4 en-affil=State Key Laboratory of Precision Geodesy, University of Science and Technology of China kn-affil= affil-num=5 en-affil=SKLab]DeepMinE, MOEKLab]OBCE, School of Earth and Space Sciences, Peking University kn-affil= affil-num=6 en-affil=Center for High]Pressure Science and Technology Advance Research kn-affil= affil-num=7 en-affil=Deutsches Elektronen]Synchrotron DESY kn-affil= affil-num=8 en-affil=Center for High]Pressure Science and Technology Advance Research kn-affil= affil-num=9 en-affil=Institute for Planetary Materials, Okayama University kn-affil= en-keyword=hydrogen-bond symmetrization kn-keyword=hydrogen-bond symmetrization en-keyword=(Al,H)-bearing CaCl2-type SiO2 kn-keyword=(Al,H)-bearing CaCl2-type SiO2 en-keyword=deep-water cycle kn-keyword=deep-water cycle en-keyword=high temperature and high pressure kn-keyword=high temperature and high pressure END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=9 article-no= start-page=e70208 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Proton]Radiation]Tolerant Silicon Photonic Charge Sensor for Spacecraft Applications en-subtitle= kn-subtitle= en-abstract= kn-abstract=Silicon waveguides are promising platforms for spacecraft potential sensing owing to their compactness and immunity to electromagnetic interference. However, proton-induced optical absorption in operating silicon waveguides has not been quantitatively clarified, despite their direct exposure to the space radiation environment during spacecraft operation. Here, we present a systematic elucidation of proton-radiation effects on a photonic charge sensor based on silicon photonic crystal waveguides. During proton irradiation at 20 keV, we quantitatively evaluate the increase in optical absorption under device operation and find that a fluence of 1.0 ~1014 cm? 2 induces an additional absorption coefficient of approximately 0.41 cm? 1 . We further demonstrate that the sensor retains its ability to measure spacecraft potential even after exposure to a high proton fluence of 1.0 ~1015 cm? 2 , confirming its intrinsic radiation tolerance. These results establish the radiation robustness of silicon-waveguide- based sensing mechanisms and provide the first quantitative basis for implementing photonic charge sensors in radiation-rich spacecraft environments. en-copyright= kn-copyright= en-aut-name=TakahamaWataru en-aut-sei=Takahama en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtsukaKosei en-aut-sei=Otsuka en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshiharaAyumi en-aut-sei=Ishihara en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HojoRikuto en-aut-sei=Hojo en-aut-mei=Rikuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MogamiTomofumi en-aut-sei=Mogami en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ToyodaKazuhiro en-aut-sei=Toyoda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzukiKohtaku en-aut-sei=Suzuki en-aut-mei=Kohtaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakahashiYasushi en-aut-sei=Takahashi en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Physics and Electronics, Osaka Metropolitan University kn-affil= affil-num=2 en-affil=Department of Physics and Electronics, Osaka Metropolitan University kn-affil= affil-num=3 en-affil=Department of Physics and Electronics, Osaka Metropolitan University kn-affil= affil-num=4 en-affil=Department of Space Systems Engineering, Kyushu Institute of Technology kn-affil= affil-num=5 en-affil=ElectrostaticEngineering DEPT, Kasuga Denki INC kn-affil= affil-num=6 en-affil=Department of Space Systems Engineering, Kyushu Institute of Technology kn-affil= affil-num=7 en-affil=Research and Development, The Wakasa Wan Energy Research Center kn-affil= affil-num=8 en-affil=Faculty of Environmental, Life, Natural Science and Technology,Okayama University kn-affil= en-keyword=photonic crystal waveguides kn-keyword=photonic crystal waveguides en-keyword=potential sensors kn-keyword=potential sensors en-keyword=radiation-tolerant sensors kn-keyword=radiation-tolerant sensors en-keyword=space silicon photonics kn-keyword=space silicon photonics en-keyword=spacecrafts charging kn-keyword=spacecrafts charging END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=26 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Incidence and survival outcomes of myocarditis and pericardial diseases associated with immune checkpoint inhibitor therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Immune checkpoint inhibitor(ICI) induced cardiac immune related adverse events are challenging to study; Leveraging large data bases like TriNetX global health network may provide needed insights.
Methods We performed a retrospective cohort study including patients diagnosed neoplasm and 18 and older when receiving ICI therapy from 1/1/2011 to 12/31/2022. Queried ICD 9/10 codes identified patients experiencing myocarditis, pericarditis, pericardial effusion, and cardiac tamponade within 1 year of ICI initiation. Survival analyses compared one-year overall survival (OS) of patients experiencing cardiac irAEs against propensity score matched populations not experiencing them.
Results In 88,928 identified ICI patients, the incidence of myocarditis(0.48%), pericarditis(0.22%), and cardiac tamponade(0.47%) were less than 1% while pericardial effusion occurred in 4.71% of patients. Hazard ratios (HRs) were significantly higher in all cardiac irAE groups: myocarditis (HR:1.26, 95% CI:1.04?1.54, p?=?0.02), pericarditis (HR:1.36, 95% CI:1.02?1.82, p?=?0.04), pericardial effusion (HR:1.49, 95% CI:1.39?1.59, p? Discussion/conclusion Utilizing a uniquely large cohort of ICI patients, this study further shows the rarity of cardiac inflammatory irAEs and highlights their significant impact on patient survival. en-copyright= kn-copyright= en-aut-name=OzakiAya F. en-aut-sei=Ozaki en-aut-mei=Aya F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SayerMichael en-aut-sei=Sayer en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagasakaMisako en-aut-sei=Nagasaka en-aut-mei=Misako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LeeBenjamin J. en-aut-sei=Lee en-aut-mei=Benjamin J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DohJean en-aut-sei=Doh en-aut-mei=Jean kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaqviAli en-aut-sei=Naqvi en-aut-mei=Ali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NowrouziNareh en-aut-sei=Nowrouzi en-aut-mei=Nareh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=PatelPranav M. en-aut-sei=Patel en-aut-mei=Pranav M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= affil-num=2 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= affil-num=3 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Hematology and Oncology, University of California kn-affil= affil-num=5 en-affil=Department of Pharmacy, University of California kn-affil= affil-num=6 en-affil=Department of Pharmacy, University of California kn-affil= affil-num=7 en-affil=Division of Cardiology, Department of Medicine, University of California kn-affil= affil-num=8 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= affil-num=9 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=10 en-affil=Division of Cardiology, Department of Medicine, University of California kn-affil= en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors en-keyword=Myocarditis kn-keyword=Myocarditis en-keyword=Cardiotoxicity kn-keyword=Cardiotoxicity en-keyword=Immune-related adverse events kn-keyword=Immune-related adverse events en-keyword=Overall survival kn-keyword=Overall survival END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e77909 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260927 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SPRED2 Negatively Regulates CD8+ T Cell-Mediated Antitumor Immunity in Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Activation of the RAS/RAF/ERK pathway is crucial for adaptive immunity. Here, we provide evidence that Sprouty-related EVH1 domain containing 2 (SPRED2), an endogenous inhibitor of this pathway, negatively regulates CD8+ T cell-mediated antitumor immunity in breast cancer. In EO771 and 4T1 mouse models, Spred2?/? mice exhibit reduced tumor growth, with lower endpoint lung metastatic burden in the 4T1 model, accompanied by increased T-cell infiltration and activation. Spred2?/? T cells show enhanced cytokine expression, proliferation,survival, in vitro cytotoxicity, and memory-like phenotypes, particularly among CD8+ T cells. Adoptive transfer of Spred2?/? CD8+ T cells into tumor-bearing wild-type hosts similarly reduces endpoint lung metastatic burden. MEK inhibition with U0126 attenuates increased interferon-gamma and granzyme B expression in Spred2?/? CD8+ T cells. Transcriptomic analyses reveal an inverse correlation between SPRED2 expression and antitumor CD8+ T cell states in both humans and mice. In tumor-infiltrating T cells from patients with breast cancer, SPRED2low T cells show enriched effector and cytotoxicity programs and are associated with gimmune-hoth tumors, whereas survival associations vary with CD8+ T cell context. Collectively, these findings suggest that SPRED2 functions as a cell-intrinsic negative regulator of CD8+ T-cell activation and highlight its potential as a therapeutic target to enhance T cell?based cancer immunotherapy. en-copyright= kn-copyright= en-aut-name=TianMiao en-aut-sei=Tian en-aut-mei=Miao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZhaoKun en-aut-sei=Zhao en-aut-mei=Kun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiChunning en-aut-sei=Li en-aut-mei=Chunning kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GaoTong en-aut-sei=Gao en-aut-mei=Tong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Advanced International and Information Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=CD8+ T cells kn-keyword=CD8+ T cells en-keyword=immunotherapy kn-keyword=immunotherapy en-keyword=MAPK/ERK kn-keyword=MAPK/ERK en-keyword=tumor microenvironment kn-keyword=tumor microenvironment END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue=1 article-no= start-page=e15868 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A case of fetal myocardial calcification with hyperechoic area in fetal echocardiography en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SatoTakeshi en-aut-sei=Sato en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WashioYosuke en-aut-sei=Washio en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BabaKenji en-aut-sei=Baba en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EtoEriko en-aut-sei=Eto en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=myocardial calcification kn-keyword=myocardial calcification END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=5 article-no= start-page=573 end-page=583 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tob negatively regulates NF-ƒÈB activation in breast cancer through its association with the TNF receptor complex en-subtitle= kn-subtitle= en-abstract= kn-abstract=NF-ƒÈB mediates transcriptional regulation crucial to many biological functions, and elevated NF-ƒÈB activity leads to autoimmune and inflammatory diseases, as well as cancer. Since highly aggressive breast cancers have few therapeutic molecular targets, clarification of key molecular mechanisms of NF-ƒÈB signaling would facilitate the development of more effective therapy. In this report, we show that Tob, a member of the Tob/BTG family of antiproliferative proteins, acts as a negative regulator of the NF-ƒÈB signal in breast cancer. Studies with 35 human breast cancer cell lines reveal that Tob expression is negatively correlated with NF-ƒÈB activity. Analysis of The Cancer Genome Atlas (TCGA) database of clinical samples reveals an inverse correlation between Tob expression and NF-ƒÈB activity. Tob knockdown in human breast cancer cells promoted overactivation of NF-ƒÈB upon TNF-ƒ¿ treatment, whereas overexpression of Tob inhibited TNF-ƒ¿ stimulation-dependent NF-ƒÈB activation. Mechanistically, Tob associates with the TNF receptor complex I and consequently inhibits RIPK1 polyubiquitylation, leading to possible prevention of overwhelming activation of NF-ƒÈB. en-copyright= kn-copyright= en-aut-name=TokumasuMiho en-aut-sei=Tokumasu en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoAtsuko en-aut-sei=Sato en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Ito-KurehaTaku en-aut-sei=Ito-Kureha en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoMizuki en-aut-sei=Yamamoto en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhmineNao en-aut-sei=Ohmine en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SembaKentaro en-aut-sei=Semba en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=InoueJun-ichiro en-aut-sei=Inoue en-aut-mei=Jun-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University kn-affil= affil-num=3 en-affil=Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University kn-affil= affil-num=4 en-affil=Research Center for Asian Infectious Diseases, The Institute of Medical Science, The University of Tokyo kn-affil= affil-num=5 en-affil=Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University kn-affil= affil-num=6 en-affil=Department of Life Science and Medical Bioscience, Waseda University kn-affil= affil-num=7 en-affil=The University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA) kn-affil= affil-num=8 en-affil=Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University kn-affil= 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=16 cd-vols= no-issue=8 article-no= start-page=e106715 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Study protocol for a phase II clinical trial evaluating the safety and efficacy of favipiravir injection combined with oseltamivir in influenza treatment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Older adults are at an increased risk of influenza-related hospitalisation and mortality due to a combination of risk factors. Severe influenza and excess mortality in this population remain major public health concerns, underscoring the need for novel treatment strategies.
Methods and analysis This multicentre, investigator-initiated, randomised, double-blind clinical trial evaluated the efficacy and safety of the investigational drug favipiravir injection (T-705IV) in combination with oseltamivir phosphate, compared with oseltamivir monotherapy in hospitalised patients with influenza aged ?65 years. Both T-705IV and oseltamivir phosphate will be administered for 5?days. The primary endpoint is time from randomisation to recovery within 15 days. Recovery is defined as either actual hospital discharge or sustained clinical status permitting discharge for 3 consecutive days. Clinical status will be assessed using a 7-point ordinal scale based on hospitalisation status and oxygen requirement. The primary analysis employs a Bayesian Cox proportional hazards model with a non-informative prior to estimate the posterior probability that the HR exceeds 1.0. The secondary endpoints include the distribution of 7-point scale scores over a 29-day period; rates of clinical worsening at days 15 and 29; duration of fever; all-cause mortality; intensive care unit admission within 29 days; pneumonia complication rate at 15 days; and changes in viral titre and viral RNA load on days 1, 2, 3 and 7. Safety will be assessed through the collection of adverse events (AEs) up to day 29. Pharmacokinetic evaluation will include measurement of plasma favipiravir concentrations on day 3. The planned sample size is 80 patients (40 per group).
Ethics and dissemination Written informed consent will be obtained from all participants. This study was approved by the Center Hospital of the National Center for Global Health and Medicine Institutional Review Board (approval number: NCGM-I-022-24a) and registered in the Japan Registry of Clinical Trials. Study findings will be disseminated through peer-reviewed publications and/or presentations at academic conferences.
Trial registration number jRCT2031240586, en-copyright= kn-copyright= en-aut-name=HikidaSayaka en-aut-sei=Hikida en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomotoHidetoshi en-aut-sei=Nomoto en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UemuraYukari en-aut-sei=Uemura en-aut-mei=Yukari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiTadaki en-aut-sei=Suzuki en-aut-mei=Tadaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IzumikawaKoichi en-aut-sei=Izumikawa en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhgeHiroki en-aut-sei=Ohge en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamatoMasaya en-aut-sei=Yamato en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatoYasuyuki en-aut-sei=Kato en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HaseRyota en-aut-sei=Hase en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AoyagiTetsuji en-aut-sei=Aoyagi en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NukuiYoko en-aut-sei=Nukui en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoKazuko en-aut-sei=Yamamoto en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakesueYoshio en-aut-sei=Takesue en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SawadaKota en-aut-sei=Sawada en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimizuYosuke en-aut-sei=Shimizu en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MiyamotoSho en-aut-sei=Miyamoto en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TamuraNamiko en-aut-sei=Tamura en-aut-mei=Namiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TakahashiKozue en-aut-sei=Takahashi en-aut-mei=Kozue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SaitoSho en-aut-sei=Saito en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MiyazakiKazuki en-aut-sei=Miyazaki en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MorinoEriko en-aut-sei=Morino en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TokitaDaisuke en-aut-sei=Tokita en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OhmagariNorio en-aut-sei=Ohmagari en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= affil-num=1 en-affil=Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security kn-affil= affil-num=2 en-affil=Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security kn-affil= affil-num=3 en-affil=Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=4 en-affil=Department of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=5 en-affil=Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=6 en-affil=Project Research Center for Nosocomial Infectious Diseases, Hiroshima University kn-affil= affil-num=7 en-affil=Infectious Diseases Center, Rinku General Medical Center kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, International University of Health and Welfare Narita Hospital kn-affil= affil-num=9 en-affil=Department of Infectious Diseases, Japanese Red Cross Narita Hospital kn-affil= affil-num=10 en-affil=Department of Clinical Microbiology and Infection, Tohoku University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Infection Control & Laboratory Medicine, Kyoto Prefectural University of Medicine kn-affil= affil-num=13 en-affil=First Department of Internal Medicine, Division of Infectious, Respiratory, and Digestive Medicine, University of the Ryukyus Graduate School of Medicine kn-affil= affil-num=14 en-affil=Chita Peninsula General Medical Organization, Rinku Hospital kn-affil= affil-num=15 en-affil=Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=16 en-affil=Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=17 en-affil=Department of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=18 en-affil=Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security kn-affil= affil-num=19 en-affil=Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security kn-affil= affil-num=20 en-affil=Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security kn-affil= affil-num=21 en-affil=Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=22 en-affil=Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=23 en-affil=Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=24 en-affil=Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260918 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Macroscopic and microscopic visualization of Pseudomonas syringae pv. tabaci infection using complementary bioluminescent and fluorescent reporter systems en-subtitle= kn-subtitle= en-abstract= kn-abstract=The development of bioluminescent and fluorescent reporter systems has enabled visualization of plant-pathogenic bacterial infection dynamics, providing insights into detailed mechanisms of infection and potential applications for disease control. Pseudomonas syringae pv. tabaci 6605 (Pta) possesses quorum sensing systems and produces fluorescent pigments, which make it difficult to directly apply commonly used reporter systems. In this study, we first constructed a homologous recombination-based genomic insertion system for stable chromosomal integration of reporter genes in Pta. Using this system, we established a LuxCDABE bioluminescent system driven by the nptII promoter, which successfully enabled macroscale tracking of bacterial populations during infection. We then attempted to construct an sGFP fluorescent reporter using the same nptII promoter. However, the endogenous autofluorescence of Pta masked the sGFP signal, making quantitative detection difficult. To overcome this autofluorescence problem, we screened constitutively highly expression promoters based on transcriptome data and identified two effective promoters suitable for fluorescent monitoring of Pta infection. Together with the LuxCDABE system, this integrated platform provides comprehensive spatiotemporal analysis of virulence mechanisms and plant defense responses in the Pta pathosystem, with potential applicability to other plant-pathogenic bacteria. en-copyright= kn-copyright= en-aut-name=KuroeKana en-aut-sei=Kuroe en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=IshigaYasuhiro en-aut-sei=Ishiga en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=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= 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=Faculty of Life and Environmental Sciences, University of Tsukuba 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=Pseudomonas syringae pv. tabaci kn-keyword=Pseudomonas syringae pv. tabaci en-keyword=LuxCDABE kn-keyword=LuxCDABE en-keyword=sGFP-reporter kn-keyword=sGFP-reporter END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e00747-26 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Complete genome sequence of Helicobacter pylori strain NY43 harboring bacteriophage KHP30 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The Helicobacter pylori NY43 strain spontaneously releases the bacteriophage (phage) KHP30. Here, we report the complete genome sequence of H. pylori NY43. In addition to the chromosome of H. pylori NY43, we successfully obtained the complete sequence of the episomal prophage KHP30. en-copyright= kn-copyright= en-aut-name=TakahashiMichiko en-aut-sei=Takahashi en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaedaHiromichi en-aut-sei=Maeda en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SeoSatoru en-aut-sei=Seo en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakeuchiHiroaki en-aut-sei=Takeuchi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 ORCID= affil-num=1 en-affil=Department of Surgery, Kochi Medical School, Kochi University kn-affil= affil-num=2 en-affil=Department of Surgery, Kochi Medical School, Kochi University kn-affil= affil-num=3 en-affil=Department of Surgery, Kochi Medical School, Kochi University kn-affil= affil-num=4 en-affil=Department of Medical Laboratory Sciences, Health and Science, International University of Health and Welfare Graduate School kn-affil= affil-num=5 en-affil=Department of Infectious Diseases, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Surgery, Kochi Medical School, Kochi University kn-affil= en-keyword=Helicobacter pylori kn-keyword=Helicobacter pylori en-keyword=chromosome organization kn-keyword=chromosome organization en-keyword=bacteriophage episome kn-keyword=bacteriophage episome END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=9986 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260820 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=RNase-mediated defence and its association with SCCmec in Staphylococcus aureus en-subtitle= kn-subtitle= en-abstract= kn-abstract=The rise of antibiotic resistance in Staphylococcus aureus is a major threat to global health. Resistance often emerges when bacteria acquire foreign DNA elements, such as the SCCmec cassette that makes strains resistant to nearly all ƒÀ-lactam antibiotics. Yet, not all S. aureus lineages take up these elements equally, raising the question of what prevents some strains from becoming drug-resistant. Here we identify a previously unknown defence factor that explains this mystery in a common skin lineage (ST188), frequently isolated from patients with atopic dermatitis. Such defence factor is encoded by a gene, which we name sadR, that is present in methicillin-susceptible ST188 strains but absent from resistant counterparts. SadR exhibits RNase activity that provides anti-bacteriophage and anti-plasmid defence, thus acting as a barrier to the uptake of mobile genetic elements. Gene sadR is found in methicillin-susceptible strains in S. aureus lineages other than ST188, and is consistently located adjacent to rlmH, the canonical SCCmec integration site. Moreover, SadR homologues are widespread across staphylococci and other bacteria suggesting a previously unrecognised family of RNase-based defence systems. en-copyright= kn-copyright= en-aut-name=KondoKohei en-aut-sei=Kondo en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AzamAa Haeruman en-aut-sei=Azam en-aut-mei=Aa Haeruman kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HisatsuneJunzo en-aut-sei=Hisatsune en-aut-mei=Junzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OjimaShinjiro en-aut-sei=Ojima en-aut-mei=Shinjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChiharaKotaro en-aut-sei=Chihara en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraTomohiro en-aut-sei=Nakamura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TamuraAzumi en-aut-sei=Tamura en-aut-mei=Azumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamashitaWakana en-aut-sei=Yamashita en-aut-mei=Wakana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanoSatoshi en-aut-sei=Nakano en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KutsunoShoko en-aut-sei=Kutsuno en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SugawaraYo en-aut-sei=Sugawara en-aut-mei=Yo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AmagaiMasayuki en-aut-sei=Amagai en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamaguchiTetsuo en-aut-sei=Yamaguchi en-aut-mei=Tetsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IshiiYoshikazu en-aut-sei=Ishii en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=WatashiKoichi en-aut-sei=Watashi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakahashiYoshimasa en-aut-sei=Takahashi en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KigaKotaro en-aut-sei=Kiga en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SugaiMotoyuki en-aut-sei=Sugai en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=2 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=3 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=4 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=5 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=6 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=7 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=8 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=9 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=10 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=11 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=12 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Dermatology, Keio University School of Medicine kn-affil= affil-num=14 en-affil=Department of Microbiology and Infectious Diseases, Toho University School of Medicine kn-affil= affil-num=15 en-affil=Department of Microbiology and Infectious Diseases, Toho University School of Medicine kn-affil= affil-num=16 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=17 en-affil=Research Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=18 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=19 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260623 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-term association between the COVID-19 pandemic and language development at 3 years of age en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Few studies have examined the long-term association between the COVID-19 pandemic and language development in preschoolers or its effect modifiers. We therefore examined this association during health checkups of 3-year-olds in Japan.
Methods: This repeated cross-sectional study included 40,898 3-year-olds who underwent checkups in Okayama City, Japan. We compared children examined before (2017?2019) and during the pandemic (2020?2023). The primary outcome was physician-determined risk of language difficulties. The secondary outcome was childrenfs infrequent questions using words such as gwhat,h gwho,h and gwhere.h Modified Poisson regression estimated RRs adjusted for confounders. Subgroup analyses examined effect modification by sex, childcare setting, and family size.
Results: The COVID-19 pandemic was associated with increased risk of language difficulties (RR 1.52, 95% CI 1.35?1.72). The association peaked in fiscal year 2021 and remained elevated throughout the pandemic. Secondary outcome showed elevated risk (RR 1.16, 95% CI 1.05?1.29). Girls and home-care children showed higher RRs than boys and preschool attendees.
Conclusions: The COVID-19 pandemic was associated with risk of language difficulties among 3-year-old children, with associations varying by sex and childcare setting. These findings suggest the importance of maintaining social interaction opportunities for young children during public health crises. en-copyright= kn-copyright= en-aut-name=MatsuoRumi en-aut-sei=Matsuo en-aut-mei=Rumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraKazue en-aut-sei=Nakamura en-aut-mei=Kazue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=3 article-no= start-page=e0344384 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Incidence of pelvic fractures after definitive radiotherapy for cervical cancer: A retrospective multicenter cohort study (The IPFAR study) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective
This multicenter study aimed to identify the risk factors for pelvic insufficiency fractures (PIFs) in women who received definitive radiotherapy (RT) as the initial treatment for cervical cancer and to examine the differences in the incidence of PIFs across institutions.
Patients and Methods The medical records of 208 women were reviewed. These women received definitive RT as an initial treatment for cervical cancer at four institutions between January 2016 and December 2018.
Results
The median age was 61.5 years (range: 29?93 years). Overall, 59 patients (28.4%) developed PIF, with 48 (81.4%) of them developing it within two years after completion of RT. Multivariate analysis identified postmenopausal status and treating institution as independent risk factors. The incidence of PIF varied significantly among institutions, ranging from 18.9% to 50.0%, despite no significant differences in patient demographics or RT protocols.
Conclusion
Substantial inter-institutional variation in PIF incidence was observed, even under standardized treatment conditions. These findings underscore the need for individualized risk assessment and institutional quality control in the long-term management of cervical cancer survivors. en-copyright= kn-copyright= en-aut-name=ShirakawaShinsuke en-aut-sei=Shirakawa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshioKotaro en-aut-sei=Yoshio en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImafukuNoriaki en-aut-sei=Imafuku en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoDan en-aut-sei=Yamamoto en-aut-mei=Dan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YorimitsuMasae en-aut-sei=Yorimitsu en-aut-mei=Masae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KodamaJunichi en-aut-sei=Kodama en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagasakaHisako en-aut-sei=Nagasaka en-aut-mei=Hisako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakanishiYoshie en-aut-sei=Nakanishi en-aut-mei=Yoshie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Okayama University kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Okayama University kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Fukuyama Medical Center kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Fukuyama Medical Center kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=60 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260920 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Carbon solubility and liquid?liquid immiscibility in Fe?C?S ternary system up to 6?GPa: implications for the core of small planetary bodies en-subtitle= kn-subtitle= en-abstract= kn-abstract=High-pressure, high-temperature experiments were conducted in a multi-anvil press using seven different starting compositions to investigate the phase relations of Fe?C?S liquids at pressures up to 6 GPa and temperatures up to 2000 K. Quenched samples revealed immiscible C-rich and S-rich metallic liquids at 2 and 4 GPa, manifesting as either large immiscible zones or emulsified smaller droplets. On the contrary, no immiscibility was observed at 5 or 6 GPa. At these higher pressures, the carbon solubility limit, significantly reduced by increasing sulfur content in the ternary liquid, prevents the formation of a liquid phase rich in both C and S. Our findings thus indicate that super-liquidus immiscibility in Fe-rich compositions does not occur at pressures above 5 GPa, due to the differential pressure dependence of C solubility and miscibility. The limited C solubility in S-rich liquids at higher pressures effectively suppresses immiscibility. Based on these results, terrestrial planetary bodies with fluid cores at pressures exceeding 5 GPa are unlikely to experience liquid?liquid immiscibility, even when both carbon and sulfur are abundant, as sulfur limits carbon solubility and promotes its exsolution. For the Moon, immiscibility-induced core stratification is not expected, though local emulsification could occur near the core?mantle boundary (CMB). In smaller bodies, a two-liquid Fe?C?S core may form at high temperatures, but progressive cooling may lead to graphite crystallization and the potential development of a graphitic crust. en-copyright= kn-copyright= en-aut-name=ZhaoBin en-aut-sei=Zhao en-aut-mei=Bin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MorardGuillaume en-aut-sei=Morard en-aut-mei=Guillaume kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ManthilakeGeeth en-aut-sei=Manthilake en-aut-mei=Geeth kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ParisiadesParaskevas en-aut-sei=Parisiades en-aut-mei=Paraskevas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YangJing en-aut-sei=Yang en-aut-mei=Jing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FeiYingwei en-aut-sei=Fei en-aut-mei=Yingwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Le GodecYann en-aut-sei=Le Godec en-aut-mei=Yann kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KondoNozomi en-aut-sei=Kondo en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshinoTakashi en-aut-sei=Yoshino en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AntonangeliDaniele en-aut-sei=Antonangeli en-aut-mei=Daniele kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=UMR CNRS 7590, Institut de Min?ralogie, de Physique des Mat?riaux et de Cosmochimie, IMPMC, Mus?um National dfHistoire Naturelle, Sorbonne Universit? kn-affil= affil-num=3 en-affil=Laboratoire Magmas et Volcans, Universit? Clermont-Auvergne kn-affil= affil-num=4 en-affil=UMR CNRS 7590, Institut de Min?ralogie, de Physique des Mat?riaux et de Cosmochimie, IMPMC, Mus?um National dfHistoire Naturelle, Sorbonne Universit? kn-affil= affil-num=5 en-affil=Earth and Planets Laboratory, Carnegie Institution for Science kn-affil= affil-num=6 en-affil=Earth and Planets Laboratory, Carnegie Institution for Science kn-affil= affil-num=7 en-affil=UMR CNRS 7590, Institut de Min?ralogie, de Physique des Mat?riaux et de Cosmochimie, IMPMC, Mus?um National dfHistoire Naturelle, Sorbonne Universit? kn-affil= affil-num=8 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=9 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=10 en-affil=UMR CNRS 7590, Institut de Min?ralogie, de Physique des Mat?riaux et de Cosmochimie, IMPMC, Mus?um National dfHistoire Naturelle, Sorbonne Universit? kn-affil= en-keyword=Iron?carbon?sulfur liquids kn-keyword=Iron?carbon?sulfur liquids en-keyword=Miscibility kn-keyword=Miscibility en-keyword=High pressure and high temperature kn-keyword=High pressure and high temperature en-keyword=Planetary cores kn-keyword=Planetary cores END start-ver=1.4 cd-journal=joma no-vol= 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 ƒ¿-Al dendrite, Al?Si eutectic and primary Si, while their area fractions (fƒ¿-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: fƒ¿-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 fƒ¿-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 ƒ¿-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=85 cd-vols= no-issue=13 article-no= start-page=317 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=Intensity of chemical weathering and its implications for soil erosion across lithological and climatic gradients in the Chemoga watershed, Upper Blue Nile Basin en-subtitle= kn-subtitle= en-abstract= kn-abstract=The geochemistry of rocks, regolith/soil, surficial and core sediments, and clay mineral assemblages from these sediments was analyzed to elucidate the transition from fresh to chemically altered materials. These data were used to evaluate the intensity of chemical weathering and its implications for erosion across contrasting lithological and climatic gradients in the Chemoga watershed of the Upper Blue Nile Basin, Ethiopia. Our findings show depletion of Na+, Ca2+, Mg2+, and K+, and enrichment of Al3+, Fe3+, Ti4+, and Mn2+ in the regolith/soil, upper part of surficial sediment, and upper layer of the core sediment (10 m). Chemical Index of Alteration (CIA) values are rocks 35?47, regolith/soil 75?96, surficial river sediments 45?96, and core sediments 50?90. River sediments in the highland area are dominated by kaolinite (39%), illite (34%), and chlorite (27%), while the lower study area has illite (76%), chlorite (11%), and kaolinite (12%). Geochemistry, ternary plots, and clay mineralogy show that the highland region underwent intensive chemical weathering, while the midland experienced intermediate to high weathering, and the lowland had weak weathering. The highlands experience severe weathering due to a humid, bimodal precipitation climate; despite having younger, weathering-resistant rocks (basalt, andesite, trachyte), the lower regions consist of older, more mafic rocks (basalt and trachybasalt). Like the surficial river sediment, core sediment showed intense chemical weathering and kaolinite dominance in the upper layers (0?10 m depth, CIA?>?80). Weathering intensity decreased with depth, suggesting changes in weathering and in clay mineral formation that reflect past climate. The high weathering gradient from highland to lowland correlates with erosion, indicating that weathering strongly influences soil erosion variability in the watershed. This work provides a reasonable basis for improving our understanding of the degree of weathering across contrasting environments and its implications for soil erosion by connecting the relationship between parent materials and chemically altered samples with the degree of soil erosion. en-copyright= kn-copyright= en-aut-name=KehaliAlebachew Tareke en-aut-sei=Kehali en-aut-mei=Alebachew Tareke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=HaregeweynNigussie en-aut-sei=Haregeweyn en-aut-mei=Nigussie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuboMitsuru en-aut-sei=Tsubo en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AntenehZelalem Leyew en-aut-sei=Anteneh en-aut-mei=Zelalem Leyew kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AyalewBelay Tesfa en-aut-sei=Ayalew en-aut-mei=Belay Tesfa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TerefeZena Tessema en-aut-sei=Terefe en-aut-mei=Zena Tessema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BelayAshebir Sewale en-aut-sei=Belay en-aut-mei=Ashebir Sewale kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FentaAyele Almaw en-aut-sei=Fenta en-aut-mei=Ayele Almaw kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsunekawaAtsushi en-aut-sei=Tsunekawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=The United Graduate School of Agricultural Sciences, Tottori University kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=International Platform for Dryland Research and Education, Tottori University kn-affil= affil-num=4 en-affil=International Platform for Dryland Research and Education, Tottori University kn-affil= affil-num=5 en-affil=Department of Geology, School of Earth Sciences, Bahir Dar University kn-affil= affil-num=6 en-affil=Department of Geology, School of Earth Sciences, Bahir Dar University kn-affil= affil-num=7 en-affil=The United Graduate School of Agricultural Sciences, Tottori University kn-affil= affil-num=8 en-affil=Department of Geology, School of Earth Sciences, Bahir Dar University kn-affil= affil-num=9 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=10 en-affil=Institute for Planetary Materials, Okayama University kn-affil= en-keyword=Geochemistry kn-keyword=Geochemistry en-keyword=Clay mineralogy kn-keyword=Clay mineralogy en-keyword=Core sediment kn-keyword=Core sediment en-keyword=Chemical Index of Alteration kn-keyword=Chemical Index of Alteration en-keyword=Climate kn-keyword=Climate END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=e70330 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Transcystostomal Bladder Tumor Resection in a Transgender Man After Phalloplasty en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction
Phalloplasty in transgender men is frequently complicated by a neourethral stricture, precluding standard transurethral access for bladder tumor resection. We describe the first reported case of a transcystostomal bladder tumor resection in a transgender man after a radial forearm free flap (RFFF) phalloplasty.
Materials and Surgical Technique
A 65-year-old transgender man, 23?years after an RFFF phalloplasty, presented with gross hematuria and a 15-mm posterior bladder tumor. A 7.95?Fr flexible ureteroscope reached the bladder but with markedly limited maneuverability. A two-stage transcystostomal approach was used: a 14?Fr suprapubic cystostomy (SPC) was placed 1?month before resection for tract maturation, followed by balloon dilation and insertion of a 24?Fr resectoscope. The modified Valdivia position enabled simultaneous transcystostomal and transurethral access with gravity-assisted irrigation drainage. Complete tumor resection was achieved without complications, and pathology confirmed noninvasive papillary urothelial carcinoma (pTa, low-grade) with negative margins. A single immediate intravesical instillation of pirarubicin was administered. Surveillance cystoscopy via the cystostomy tract at 3 and 6?months revealed no recurrence; the patient continues to void while standing with the cystostomy catheter capped.
Discussion
The two-stage transcystostomal approach, combining prior SPC placement, balloon tract dilation, and the modified Valdivia position, enabled safe oncological control while preserving phallic anatomy and standing voiding function. This technique offers a reproducible option for bladder tumor resection in patients with functionally inadequate transurethral access after phalloplasty. en-copyright= kn-copyright= en-aut-name=MoriwakeTakatoshi en-aut-sei=Moriwake en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OzakiNariaki en-aut-sei=Ozaki en-aut-mei=Nariaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoYuko en-aut-sei=Matsumoto en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiTomoko en-aut-sei=Kobayashi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshinagaKasumi en-aut-sei=Yoshinaga en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamanoiTomoaki en-aut-sei=Yamanoi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NambaYuzaburo en-aut-sei=Namba en-aut-mei=Yuzaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Miyakekai Good Life Hospital kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Gender Center, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=bladder neoplasms kn-keyword=bladder neoplasms en-keyword=gender-affirming surgery kn-keyword=gender-affirming surgery en-keyword=phalloplasty kn-keyword=phalloplasty en-keyword=suprapubic cystostomy kn-keyword=suprapubic cystostomy en-keyword=transgender persons kn-keyword=transgender persons END start-ver=1.4 cd-journal=joma no-vol=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=34 cd-vols= no-issue=8 article-no= start-page=809 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260729 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Machine learning approaches to predict early cardiac immune-related adverse events in patients receiving immune checkpoint inhibitors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Immune checkpoint inhibitor (ICI)?induced cardiac immune-related adverse events (cardiac irAEs) are rare yet serious complications. Clinical assessment tools to identify at-risk patients would allow for more effective prevention strategies, thus improving clinical outcomes. We constructed various machine learning (ML) models to predict these events among patients receiving ICI therapy.
Methods A cohort of patients receiving ICI therapy from 2010 to 2023 was identified from the TriNetX database. Cardiac irAEs were defined as the occurrence of relevant diagnosis codes within 90 days of ICI initiation, with corresponding hospital visits. We created ML models to predict these events, including elastic net logistic regression and multiple tree-based approaches (gradient boosted trees and random forest). We evaluated model performance with different performance measures and utilized assigned risk scores to stratify risk of cardiac irAEs into low, medium, and high-risk tiers.
Results We identified 61,117 patients receiving ICI therapy, with nearly 2% of patients experiencing cardiac irAEs. Model performance on testing data was comparable with all approaches (AUC?=?0.71?0.72, balanced accuracy?=?65?66%). Each model emphasized distinct features to make classifications, as observed with feature importance and SHAP values. Comparing cardiac irAE rates among assigned risk strata, patients identified as high risk were significantly more likely to experience cardiac irAEs compared to lower tiers.
Conclusion Our preliminary exploration of ML methods demonstrated the potential for risk assessment tools to predict rare cardiac irAEs in patients receiving ICI therapy. Follow-up studies can implement time series approaches to harness longitudinal data that incorporates real-time labs, new diagnoses, and new therapy, to refine predictions further. en-copyright= kn-copyright= en-aut-name=SayerMichael en-aut-sei=Sayer en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChangPeter D. en-aut-sei=Chang en-aut-mei=Peter D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoReina en-aut-sei=Yamamoto en-aut-mei=Reina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagasakaMisako en-aut-sei=Nagasaka en-aut-mei=Misako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NaqviAli A. en-aut-sei=Naqvi en-aut-mei=Ali A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PatelPranav M. en-aut-sei=Patel en-aut-mei=Pranav M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OzakiAya F. en-aut-sei=Ozaki en-aut-mei=Aya F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= affil-num=2 en-affil=School of Medicine, Pathology & Laboratory Medicine, University of California kn-affil= affil-num=3 en-affil=Department of Pharmacy, Medical Development Field, Okayama University kn-affil= affil-num=4 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Division of Hematology and Oncology, University of California kn-affil= affil-num=6 en-affil=Mary & Steve Wen Cardiovascular Division, Department of Medicine, University of California kn-affil= affil-num=7 en-affil=Mary & Steve Wen Cardiovascular Division, Department of Medicine, University of California kn-affil= affil-num=8 en-affil=Department of Pharmacy, Medical Development Field, Okayama University kn-affil= affil-num=9 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors en-keyword=Immune-related adverse events kn-keyword=Immune-related adverse events en-keyword=Myocarditis kn-keyword=Myocarditis en-keyword=Pericarditis kn-keyword=Pericarditis en-keyword=Machine learning kn-keyword=Machine learning en-keyword=Risk assessment tools kn-keyword=Risk assessment tools END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202607 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Seizures associated with clozapine augmentation by other antipsychotics: a pharmacovigilance?pharmacodynamic analysis using VigiBase en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Clozapine is associated with a high risk of central nervous system abnormalities. However, seizure risk related to interactions between clozapine and other antipsychotics remains poorly characterized, and the pharmacological mechanisms underlying these seizures are unclear. Objectives: We aimed to evaluate safety signals for seizures associated with clozapine augmentation by other antipsychotics and analyze the relationship between these signals and neurotransmitter receptor occupancy profiles.
Design: A pharmacovigilance?pharmacodynamic analysis using a spontaneous reporting system.
Methods: This pharmacovigilance study used VigiBase, an adverse drug reaction database maintained by the World Health Organization. Drug?drug interactions (DDIs) between clozapine and other antipsychotics were assessed using the ƒ¶ shrinkage measure model. The association between DDI signals and neurotransmitter receptor occupancy was evaluated using linear regression. Robustness was tested using four frequency statistical models: additive, multiplicative, combination risk ratio, and chi-square statistic models. Results: Of 38,758,077 reports in VigiBase between 1990 and 2024, 230,371 involved clozapine. Among antipsychotics classified under ATC code N05A, DDIs with clozapine were detected for amisulpride, chlorpromazine, haloperidol, lurasidone, olanzapine, penfluridol, risperidone, sulpiride, zotepine, and zuclopenthixol. A significant association between dopamine D4 receptor occupancy and the point estimates of signal values was observed in the ƒ¶ shrinkage measure model (ƒÀ?=?0.295, 95% confidence interval: 0.119?0.471, p?=?0.002) and replicated across all frequency statistical models.
Conclusions: These findings suggest a potential role of dopamine D4 receptor occupancy in seizures associated with clozapine augmentation by other antipsychotics. Further large-scale epidemiological studies are needed to validate these findings. en-copyright= kn-copyright= en-aut-name=HatanoMasakazu en-aut-sei=Hatano en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KandaMasaya en-aut-sei=Kanda en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KosekiTakenao en-aut-sei=Koseki en-aut-mei=Takenao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakaiTsuyoshi en-aut-sei=Nakai en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriiRina en-aut-sei=Horii en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshiharaNozomi en-aut-sei=Yoshihara en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SaitoTakeo en-aut-sei=Saito en-aut-mei=Takeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakechiKenshi en-aut-sei=Takechi en-aut-mei=Kenshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EsumiSatoru en-aut-sei=Esumi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamadaShigeki en-aut-sei=Yamada en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine kn-affil= affil-num=2 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pharmacy, Asahikawa Medical University Hospital kn-affil= affil-num=4 en-affil=Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine kn-affil= affil-num=5 en-affil=Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine kn-affil= affil-num=6 en-affil=Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine kn-affil= affil-num=7 en-affil=Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine kn-affil= affil-num=8 en-affil=Department of Psychiatry, Fujita Health University School of Medicine kn-affil= affil-num=9 en-affil=Department of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama University kn-affil= affil-num=10 en-affil=The Faculty of Pharmaceutical Sciences, Kobe Gakuin University kn-affil= affil-num=11 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=8 article-no= start-page=e00484-26 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260804 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High-throughput screening system for antimycobacterial compounds using in vitro infected cells: construction and application to compounds in the ?mura Natural Compound Library en-subtitle= kn-subtitle= en-abstract= kn-abstract=The global increase in multidrug-resistant tuberculosis strains poses a major threat; consequently, there is an urgent need to identify and develop novel drugs. We have previously presented a simple fibroblast assay (SFA) screening method that enables the simultaneous assessment of antibacterial activity and cytotoxicity toward host cells. This method was developed based on our finding that live (but not dead) Mycobacterium tuberculosis bacilli exhibit cytotoxic activity against human lung fibroblasts, and that this cytotoxicity, which is proportional to the number of viable bacterial cells, is inhibited by known antimycobacterial drugs. While conventional methods to measure M. tuberculosis growth require 2?4 weeks to detect antibacterial activity; the SFA method enables detection within 2?3 days and can detect compounds that are active within host cells. Here, we applied high-throughput screening, based on assessment of cytotoxicity, to identify candidate antimycobacterial agents. In parallel, by comparing the direct antibacterial activity of compounds in liquid medium (using the broth dilution test) with that observed via SFA, we developed a new SFA-based screening system to select compounds with low cytotoxicity that are active outside or inside the host cells. Using this dual system, we screened 742 compounds from the ?mura Natural Compound Library (Kitasato University, Japan), with 62 hits. Of these, 19 were excluded owing to their toxicity, and six exhibited antibacterial activity only via SFA screening. Four promising antimycobacterial candidates with no cytotoxicity at the 10 ƒÊg/mL threshold?aridicin A, lankamycin, streptovaricin, and lariatin A?were identified. identified.This novel system supports the rapid identification of low-cytotoxicity antimycobacterial compounds that are active inside or outside the host cells. en-copyright= kn-copyright= en-aut-name=TakiiTakemasa en-aut-sei=Takii en-aut-mei=Takemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimishimaAoi en-aut-sei=Kimishima en-aut-mei=Aoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IwatsukiMasato en-aut-sei=Iwatsuki en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeYoshihiro en-aut-sei=Watanabe en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsamiYukihiro en-aut-sei=Asami en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Mycobacterium Reference and Research, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=2 en-affil=?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=3 en-affil=?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=4 en-affil=?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=5 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=?mura Satoshi Memorial Institute, Kitasato University kn-affil= en-keyword=Mycobacterium tuberculosis kn-keyword=Mycobacterium tuberculosis en-keyword=Mycobacterium avium kn-keyword=Mycobacterium avium en-keyword=Mycobacterium abscessus kn-keyword=Mycobacterium abscessus en-keyword=fibroblasts kn-keyword=fibroblasts en-keyword=the ?mura Natural Compound Library kn-keyword=the ?mura Natural Compound Library en-keyword=antibacterial activity kn-keyword=antibacterial activity END start-ver=1.4 cd-journal=joma no-vol=2026 cd-vols= no-issue=1 article-no= start-page=1926696 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phenotypic Characterization of Porphyromonas gulae Fimbria Mutants en-subtitle= kn-subtitle= en-abstract= kn-abstract=Porphyromonas gulae has been established as a pathogen in animal periodontal disease and expresses several virulence factors, including fimbriae, lipopolysaccharide, and proteases. P. gulae fimbriae are classified into three genotypes (A, B, and C) based on the fimbrillin (fimA) gene encoding a fimbrial subunit protein. We previously reported that P. gulae organisms with type C fimbriae were clearly more virulent as compared to those with other fimbria types, though the basic function of this is not fully understood. Here, we investigated the function of fimbriae using fimA-deficient mutants. In the present study, bacterial fimbriae were related to biofilm tenacity, whereas biofilm formation was not. Also, P. gulae fimbriae are involved in bacterial adhesion and entry into gingival epithelial cells. The role of P. gulae fimbriae in bacterial pathogenicity was then determined using fimA-deficient mutants with a silkworm infection model. Additionally, P. gulae infection can induce inflammatory responses in gingival epithelial cells and also inhibit cell migration and proliferation. In contrast, a P. gulae fimA-deficient mutant did not cause several of those cellular responses. Together, the results show that fimbriae contribute to the pathogenicity of P. gulae by affecting bacterial functions and host cell interactions. en-copyright= kn-copyright= en-aut-name=InabaHiroaki en-aut-sei=Inaba en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaSho en-aut-sei=Yoshida en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NomuraRyota en-aut-sei=Nomura en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanoKazuhiko en-aut-sei=Nakano en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Matsumoto-NakanoMichiyo en-aut-sei=Matsumoto-Nakano en-aut-mei=Michiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=5 en-affil=Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka kn-affil= affil-num=6 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=biofilm kn-keyword=biofilm en-keyword=cell invasion kn-keyword=cell invasion en-keyword=cell migration kn-keyword=cell migration en-keyword=fimbriae kn-keyword=fimbriae en-keyword=periodontitis kn-keyword=periodontitis en-keyword=Porphyromonas gulae kn-keyword=Porphyromonas gulae en-keyword=silkworm larvae kn-keyword=silkworm larvae END start-ver=1.4 cd-journal=joma no-vol=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 ƒÀ-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=999 cd-vols= no-issue=2 article-no= start-page=187 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260303 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Constraining the Effects of Pre- and Post-accretionary Processes on Ryugu Insoluble Organic Matter en-subtitle= kn-subtitle= en-abstract= kn-abstract=Asteroidal and cometary fragments have been indicated as possible sources of the building blocks of life for the early Earth. Samples returned from the asteroid Ryugu are uncontaminated and contain organic matter. Such samples enable an investigation of the processes that formed and altered extraterrestrial organic matter. Here, the FTIR and Raman responses of insoluble organic matter (IOM) isolated from Ryugu particles and carbonaceous chondrites are reported. Several relationships were observed: (1) a strong positive correlation of CH2/CH3 plotted against aliphatics/C=C; (2) a strong negative correlation of CH2/CH3 plotted against ƒÂ15N and ƒÂ13C; and (3) strong negative correlations of FTIR band ratios plotted against Raman band parameters and D/G values. The data are not consistent with even moderate heating of the IOM, as indicated by CH2/CH3 ratios that are consistent with unheated carbonaceous chondrites. The C and N isotope data previously collected for each Ryugu particle preclude aqueous alteration based on our understanding of its effects on carbonaceous chondrite IOM. Mixing of several IOM endmembers was considered, but due to the similarities of the particle with the lowest CH2/CH3 ratio to the other particles in terms of its other spectroscopic parameters, this scenario was considered unlikely. Finally, the effects of irradiation were considered, and UV irradiation, in particular, was hypothesised to be the best explanation for the trends observed. Overall, the data highlight the importance of comprehensive data sets for revealing extraterrestrial processes, which could define the nature of organic matter reaching habitable environments, such as those of the Early Earth. en-copyright= kn-copyright= en-aut-name=PotiszilChristian en-aut-sei=Potiszil en-aut-mei=Christian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamanakaMasahiro en-aut-sei=Yamanaka en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtaTsutomu en-aut-sei=Ota en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakaguchiChie en-aut-sei=Sakaguchi en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitagawaHiroshi en-aut-sei=Kitagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaRyoji en-aut-sei=Tanaka en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KunihiroTak en-aut-sei=Kunihiro en-aut-mei=Tak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KobayashiKatsura en-aut-sei=Kobayashi en-aut-mei=Katsura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraEizo en-aut-sei=Nakamura en-aut-mei=Eizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=4 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=5 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=6 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=7 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=8 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=9 en-affil=Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=53 cd-vols= no-issue=13 article-no= start-page=e2025GL120078 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Limits of Water Storage in Stishovite at Deep Mantle Conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=The deep Earth water cycle is a key process in Earth's evolution. Stishovite has been proposed as a major carrier of water from the surface into the lower mantle. However, its role remains unclear because its water solubility is controversial. We investigated the water solubility of Al-free stishovite at pressures of 33?38 GPa and temperatures of 700?1200 K using in situ X-ray diffraction in an advanced multianvil apparatus. Water solubility is high, around 3 wt%, at 700 K but decreases rapidly with increasing temperature and becomes negligible (<1,000 ppm), at temperatures above 1000 K. These results suggest that pure stishovite is unlikely to transport significant amounts of water into Earth's lower mantle under comparable pressure-temperature conditions. Previously reported high water contents in pure stishovite under deep Earth conditions likely reflect the solubility of post-stishovite or experimental artifacts. en-copyright= kn-copyright= en-aut-name=WangFei en-aut-sei=Wang en-aut-mei=Fei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChanyshevArtem en-aut-sei=Chanyshev en-aut-mei=Artem kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ManLianjie en-aut-sei=Man en-aut-mei=Lianjie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SongYunke en-aut-sei=Song en-aut-mei=Yunke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangLin en-aut-sei=Wang en-aut-mei=Lin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujinoNoriyoshi en-aut-sei=Tsujino en-aut-mei=Noriyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BhatShrikant en-aut-sei=Bhat en-aut-mei=Shrikant kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FarlaRobert en-aut-sei=Farla en-aut-mei=Robert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatsuraTomoo en-aut-sei=Katsura en-aut-mei=Tomoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=2 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=3 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=4 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=5 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=6 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=7 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=8 en-affil=Deutsches Elektronen]Synchrotron DESY kn-affil= affil-num=9 en-affil=Deutsches Elektronen]Synchrotron DESY kn-affil= affil-num=10 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= en-keyword=stishovite kn-keyword=stishovite en-keyword=high pressure kn-keyword=high pressure en-keyword=deep mantle kn-keyword=deep mantle en-keyword=multianvil press kn-keyword=multianvil press en-keyword=water cycle kn-keyword=water cycle END start-ver=1.4 cd-journal=joma no-vol=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 Earthfs 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=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 Couplefs Clinic Womenfs 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 Couplefs Clinic kn-affil= affil-num=8 en-affil=Department of Radiology, Okayama Couplefs Clinic Womenfs Health Checkup Center kn-affil= affil-num=9 en-affil=Department of Radiology, Okayama Couplefs Clinic Womenfs Health Checkup Center kn-affil= affil-num=10 en-affil=Department of Medical Technology, Okayama Couplefs Clinic kn-affil= affil-num=11 en-affil=Department of Reproductive Medicine, Okayama Couplefs Clinic kn-affil= affil-num=12 en-affil=Department of Reproductive Medicine, Okayama Couplefs 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=30 cd-vols= no-issue=7 article-no= start-page=1287 end-page=1293 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Guidance on the short hydration method for cisplatin administration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cisplatin is currently used as the central agent in several cancer chemotherapy protocols because of its broad antitumor spectrum and potent antitumor effects; however, preventing cisplatin-induced renal damage and other adverse events is challenging. Recently, several clinical studies have shown that a short hydration method could prevent cisplatin-induced renal damage. In addition, appropriate magnesium supplementation and administration of forced diuretics have been shown to be renoprotective. The Japanese Lung Cancer Society Guidelines Committee has summarized the evidence of renal protection regarding cisplatin administration to provide optimal administration guidance for the cisplatin short hydration method. 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=KunimasaKei en-aut-sei=Kunimasa en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurataYasuko en-aut-sei=Kurata en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=FujisakaYasuhito en-aut-sei=Fujisaka en-aut-mei=Yasuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshikawaHitoshi en-aut-sei=Ishikawa en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= affil-num=1 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Oncology, Osaka International Cancer Institute kn-affil= affil-num=3 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Kobe City Medical Center General Hospital kn-affil= affil-num=5 en-affil=Department of Medical Oncology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=6 en-affil=QST Hospital, National Institutes for Quantum Science and Technology kn-affil= affil-num=7 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= en-keyword=Cisplatin kn-keyword=Cisplatin en-keyword=Short hydration kn-keyword=Short hydration en-keyword=Magnesium supplementation kn-keyword=Magnesium supplementation en-keyword=Forced diuretics kn-keyword=Forced diuretics 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? 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=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=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=MorookaKenfichi en-aut-sei=Morooka en-aut-mei=Kenfichi 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=25 cd-vols= no-issue=5 article-no= start-page=e70502 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260420 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=UNC45B Reduction With Aging: A Myofiber-Intrinsic Promoting Factor for Sarcopenia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Skeletal muscle mass and force decline with age, and the loss of muscle force precedes muscle atrophy. However, the underlying mechanisms remain unclear. Here, we investigated the role of the myosin co-chaperone, uncoordinated mutant number-45 myosin chaperone B (UNC45B), in regulating muscle mass and force. UNC45B expression decreased in mouse gastrocnemius muscle with age, particularly at 24?months old, and adeno-associated virus vector-mediated knockdown of Unc45b in 3-month-old mouse triceps surae muscle first reduced plantar flexor torque and then decreased gastrocnemius muscle mass. In addition, Unc45b knockdown in the triceps surae muscle resulted in lower bone mineral density. While maximum Ca2+-activated force in mechanically skinned fibers was not affected by Unc45b knockdown, Unc45b knockdown decreased the ratio of depolarization-induced force to the maximum Ca2+-activated force. We established tamoxifen-inducible skeletal muscle-specific Unc45b knockout (Unc45b imKO) mice to investigate whether the muscle atrophy and weakness due to the loss of Unc45b impacts metabolism and behavior. We found that Unc45b imKO reduced muscle mass and force at a whole-body level, but did not influence systemic glucose tolerance, insulin sensitivity, or the respiratory exchange ratio. However, Unc45b imKO mice reduced the amount of deeper non-rapid eye movement sleep, locomotor activity, and body temperature during the sleep phase. We conclude that UNC45B is essential for maintaining fast-twitch muscle mass and muscle force. In addition, Unc45b deficiency-mediated muscle loss is also associated with bone fragility, decreased body temperature, and impaired sleep quality. en-copyright= kn-copyright= en-aut-name=MishimaTaiga en-aut-sei=Mishima en-aut-mei=Taiga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagamuneTaiga en-aut-sei=Nagamune en-aut-mei=Taiga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TadaSaori en-aut-sei=Tada en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeDaiki en-aut-sei=Watanabe en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TokudaNao en-aut-sei=Tokuda en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamadaTakashi en-aut-sei=Yamada en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Hashimoto]HachiyaAkiko en-aut-sei=Hashimoto]Hachiya en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Higo]YamamotoSayaka en-aut-sei=Higo]Yamamoto en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KidoKohei en-aut-sei=Kido en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IkedoAoi en-aut-sei=Ikedo en-aut-mei=Aoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ImaiYuuki en-aut-sei=Imai en-aut-mei=Yuuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujitaRyo en-aut-sei=Fujita en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MizunoSeiya en-aut-sei=Mizuno en-aut-mei=Seiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakahashiSatoru en-aut-sei=Takahashi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OishiKatsutaka en-aut-sei=Oishi en-aut-mei=Katsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AtoSatoru en-aut-sei=Ato en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OgasawaraRiki en-aut-sei=Ogasawara en-aut-mei=Riki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=2 en-affil=Department of Life Science and Applied Chemistry, Nagoya Institute of Technology kn-affil= affil-num=3 en-affil=Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=4 en-affil=Graduate School of Sport and Health Sciences, Osaka University of Health and Sport Sciences kn-affil= affil-num=5 en-affil=Graduate School of Health Sciences, Sapporo Medical University kn-affil= affil-num=6 en-affil=Graduate School of Health Sciences, Sapporo Medical University kn-affil= affil-num=7 en-affil=Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=8 en-affil=Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=9 en-affil=Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=10 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University kn-affil= affil-num=11 en-affil=Division of Integrative Pathophysiology, Proteo]Science Center, PIAS, Ehime University kn-affil= affil-num=12 en-affil=Division of Integrative Pathophysiology, Proteo]Science Center, PIAS, Ehime University kn-affil= affil-num=13 en-affil=Division of Regenerative Medicine, Transborder Medical Research Center, Institute of Medicine, University of Tsukuba kn-affil= affil-num=14 en-affil=Laboratory Animal Resource Center in Transborder Medical Research Center, Institute of Medicine, University of Tsukuba kn-affil= affil-num=15 en-affil=Laboratory Animal Resource Center in Transborder Medical Research Center, Institute of Medicine, University of Tsukuba kn-affil= affil-num=16 en-affil=Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=17 en-affil=Faculty of Medical Science, Nippon Sport Science University kn-affil= affil-num=18 en-affil=Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= en-keyword=chaperone kn-keyword=chaperone en-keyword=muscle atrophy kn-keyword=muscle atrophy en-keyword=muscle force kn-keyword=muscle force en-keyword=sarcopenia kn-keyword=sarcopenia END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=9 article-no= start-page=1890 end-page=1900 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260616 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Event-free survival and recurrence patterns after curative resection for locally advanced head and neck squamous cell carcinoma: single-institution real-world outcomes prior to the introduction of perioperative immunotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Perioperative immune checkpoint inhibitors have improved outcomes for resectable locally advanced head and neck squamous cell carcinoma (HNSCC). However, real-world surgical outcome data based on contemporary endpoints remain limited.
Methods We retrospectively analyzed 233 patients who underwent curative-intent surgery for locally advanced HNSCC. Event-free survival (EFS) and overall survival (OS) were evaluated. Unresectable recurrence-free survival (URFS) was explored as an additional endpoint to capture post-recurrence treatment feasibility. Prognostic factors were assessed using Cox proportional hazards models.
Results The median follow-up duration was 18.2 months. The 1-year EFS and OS rates were 67.1% and 89.4%, respectively. pN2 or higher disease, venous invasion, and perineural invasion were identified as independent adverse prognostic factors. Recurrence occurred in 34.8% of patients; among these, disease control at the last follow-up was achieved in 61.7% following curative-intent salvage treatment. Salvage surgery was associated with significantly improved post-recurrence survival (p? Conclusions This study provides real-world surgical outcome data for resectable locally advanced HNSCC prior to the introduction of perioperative immunotherapy. Recurrence remains a major clinical challenge, with heterogeneous post-recurrence outcomes influenced by treatment feasibility. These findings may help inform interpretation of treatment outcomes and clinical decision-making in the evolving era of perioperative immunotherapy. en-copyright= kn-copyright= en-aut-name=MakinoTakuma en-aut-sei=Makino en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaoiYuto en-aut-sei=Naoi en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasegawaGo en-aut-sei=Hasegawa en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamasakiTakuto en-aut-sei=Yamasaki en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NodaHiroki en-aut-sei=Noda en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimotoShohei en-aut-sei=Fujimoto en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoJunya en-aut-sei=Matsumoto en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Head and neck squamous cell carcinoma kn-keyword=Head and neck squamous cell carcinoma en-keyword=Surgery kn-keyword=Surgery en-keyword=Event-free survival kn-keyword=Event-free survival en-keyword=Recurrence kn-keyword=Recurrence en-keyword=Salvage surgery kn-keyword=Salvage surgery END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260810 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Incidental detection of cancers during population-based endoscopic gastric cancer screening in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Upper gastrointestinal endoscopy traverses the full upper aerodigestive tract, unlike radiography, potentially enabling incidental detection of non-gastric malignancies. However, its population-level incidental detection rate for non-gastric upper aerodigestive tract cancers has not been systematically quantified. The aim of this study was to compare endoscopic screening with radiography and quantify detection of non-gastric upper aerodigestive tract cancers in a population-based setting.
Methods This population-based cohort study was conducted by linking the Okayama City municipal gastric cancer screening registry with the Kokuho Database (KDB) for fiscal years 2016?2021. Among 36,326 participants contributing 64,822 screening examinations (40,832 radiography; 23,990 endoscopy), diagnoses of oral cavity, pharyngeal, laryngeal, and esophageal cancer occurring within 2 months of screening were ascertained from the KDB. Generalized estimating equations with modified Poisson regression were used to estimate adjusted risk ratios (aRRs) comparing endoscopy with radiography.
Results Endoscopic screening was significantly associated with higher composite incidental detection rates for non-gastric upper aerodigestive tract cancers (95.9 vs. 34.3 per 100,000 examinations; aRR 2.94, 95% confidence interval [CI] 1.50?5.76; p?=?0.002). Specifically, esophageal cancer detection was markedly higher with endoscopy (83.4 vs. 17.1 per 100,000; aRR 5.16, 95% CI 2.16?12.32; p? Conclusions Endoscopic gastric cancer screening is associated with substantially higher incidental detection of non-gastric upper aerodigestive tract cancers, particularly esophageal cancer. These findings suggest an additional detection value for endoscopy that extends beyond its primary gastric cancer target in organized screening programs. 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=HamadaKenta en-aut-sei=Hamada en-aut-mei=Kenta 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=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimotoKenji en-aut-sei=Fujimoto en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HayaseShunsaku en-aut-sei=Hayase en-aut-mei=Shunsaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Otolaryngology?Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University kn-affil= affil-num=3 en-affil=Department of Epidemiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Otolaryngology?Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Occupational Health Data Science Center, University of Occupational and Environmental Health kn-affil= affil-num=7 en-affil=Department of Epidemiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Epidemiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Gastric cancer screening kn-keyword=Gastric cancer screening en-keyword=Endoscopy kn-keyword=Endoscopy en-keyword=Radiography kn-keyword=Radiography en-keyword=Early detection of cancer kn-keyword=Early detection of cancer en-keyword=Esophageal neoplasms kn-keyword=Esophageal neoplasms END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=44 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=GWAS and Candidate Gene Prediction of Elemental Accumulation Traits in Rice Using a Multiparental Population en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rice plants accumulate essential elements to sustain physiological processes during growth and development and to ensure the nutritional quality of the grain as a food source. However, the genetic basis of elemental accumulation and the interrelationships among elemental concentrations across different tissues remain poorly understood. To conduct breeding aimed at improving the absorption characteristics of multiple interrelated elements, genetic analysis using experimental populations that retain diversity while sharing the genetic background of cultivated varieties is effective. Here we show genetic variations in the concentrations of 13 elements (P, K, Ca, Mg, As, Cd, Cr, Cu, Fe, Mo, Mn, Ni, and Zn) in rice straw at the flowering stage and grain at the mature stage using a multi-parent advanced generation inter-cross (MAGIC) population that derived from eight cultivars including both Japonica and Indica. Comprehensive evaluation of the correlation coefficients revealed divergences in the association between grain and straw for several combinations of elements. Haplotype-based genome-wide association studies (GWAS) identified 51 and 53 quantitative trait loci (QTLs) in straw and grain, respectively. In total, the 104 QTLs were grouped into 19 clusters and 60 independent QTLs. By leveraging the haplotype information from the MAGIC population, 52 candidate genes associated with the accumulation of Ca, Mg, Cd, Cu, Fe, and Mo were efficiently predicted from these QTLs, including both previously reported and novel genes. Among them, OsMOT1;1 encoding a molybdenum transporter, was predicted to be within a QTL associated with Mo accumulation in grain on chromosome 8. OsACA9, a homolog of autoinhibited Ca??-ATPases, was predicted within a QTL related to Ca accumulation in straw on chromosome 2. In addition, an unidentified gene, OsCML6, which is presumed to be involved in calcium signaling, was predicted to be a candidate for a Ca-accumulation QTL on chromosome 11. These findings offer insights into haplotypes and putative genes associated with element accumulation and trait interrelationships, providing valuable information for optimizing plant growth and enhancing grain nutritional quality in rice breeding programs. en-copyright= kn-copyright= en-aut-name=ZhangQian en-aut-sei=Zhang en-aut-mei=Qian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FurutaTomoyuki en-aut-sei=Furuta en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KashiharaKazunari en-aut-sei=Kashihara en-aut-mei=Kazunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OgawaDaisuke en-aut-sei=Ogawa en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YonemaruJunichi en-aut-sei=Yonemaru en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaJian Feng en-aut-sei=Ma en-aut-mei=Jian Feng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoToshio en-aut-sei=Yamamoto en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Crop Science, National Agriculture and Food Research Organization kn-affil= affil-num=5 en-affil=Research Center for Agricultural Information Technology, National Agriculture and Food Research Organization kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Rice kn-keyword=Rice en-keyword=Oryza sativa L. kn-keyword=Oryza sativa L. en-keyword=Multi-parent advanced generation inter-cross population kn-keyword=Multi-parent advanced generation inter-cross population en-keyword=Element accumulation kn-keyword=Element accumulation en-keyword=GWAS kn-keyword=GWAS en-keyword=QTL kn-keyword=QTL END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=9 article-no= start-page=e0086926 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260901 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Combinations of long terminal repeat and tax protein substitutions influence bovine leukemia virus transmission through altered viral productivity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bovine leukemia virus (BLV) infection imposes a substantial economic burden on the global cattle industry. Although proviral load (PVL) in blood influences transmission, the effects of viral genetic variations, including the high viral production-associated long terminal repeat (LTR) substitution at nucleotide position 175 (LTR175), on herd-level dynamics remain unclear. This study investigated the effects of specific substitutions on the regulation of viral productivity and transmission. Longitudinal monitoring of a single farm (herd size: 50?68 cows; 438 samples collected) over a 7-year period revealed that viral strains carrying cytosine at LTR175 (LTR175C) significantly increased in frequency, becoming dominant over wild-type strains carrying thymidine. In contrast, amino acid substitutions in the Tax protein at positions 69 (Tax69) and 73 (Tax73) modified viral transactivation independent of LTR175. Structural modeling via AlphaFold2 predicted that Tax69 and Tax73 mutations alter protein properties, suggesting modulation of transactivation activity. Consistent with this prediction, in vitro assays confirmed that the substitutions modified viral production by regulating transactivation independent of LTR175. Moreover, high viral-productivity haplotypes containing LTR175C and Tax73Q (glutamine at amino acid residue 73) exhibited a transmission advantage within the herd, even when host PVL levels were not significantly elevated. These findings suggest that cellular-level viral productivity is one of the key determinants of transmission fitness. Overall, this study revealed a regulatory interaction between the LTR and Tax protein that optimizes viral spread and highlights the need for control strategies that account for viral genetic substitutions. en-copyright= kn-copyright= en-aut-name=MurakamiHironobu en-aut-sei=Murakami en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoReiichiro en-aut-sei=Sato en-aut-mei=Reiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SogawaKazuyuki en-aut-sei=Sogawa en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshidaHiroho en-aut-sei=Ishida en-aut-mei=Hiroho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagaiMakoto en-aut-sei=Nagai en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=School of Veterinary Medicine, Azabu University kn-affil= affil-num=2 en-affil=Graduate School of Medicine and Veterinary Medicine, University of Miyazaki kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=School of Life and EnvironmentaScience, Azabu University kn-affil= affil-num=5 en-affil=School of Veterinary Medicine, Azabu University kn-affil= affil-num=6 en-affil=School of Veterinary Medicine, Azabu University kn-affil= en-keyword=bovine leukemia virus kn-keyword=bovine leukemia virus en-keyword=substitution kn-keyword=substitution en-keyword=transmission kn-keyword=transmission en-keyword=haplotype kn-keyword=haplotype en-keyword=molecular clone kn-keyword=molecular clone en-keyword=proviral load kn-keyword=proviral load en-keyword=reverse genetics kn-keyword=reverse genetics END start-ver=1.4 cd-journal=joma no-vol=139 cd-vols= no-issue=2 article-no= start-page=255 end-page=265 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Knockout of a single aquaporin, OsPIP2;4, decreases root water permeability in rice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aquaporins (AQPs) are membrane proteins that facilitate water transport and are present in nearly all bacterial, animal, and plant cells. In plants, AQPs are classified into four or more subfamilies, with plasma membrane intrinsic proteins (PIPs) playing a key role in root water uptake and cellular water regulation. Previous studies have demonstrated that PIPs contribute to root hydraulic conductivity (Lpr) in various plant species. In this study, we examined the specific role of OsPIP2;4, one of the PIP-type aquaporins among 11 rice (Oryza sativa) PIP2s, in regulating Lpr. Transgenic rice plants, including OsPIP2;4-knockout (KO) and overexpressing (Ox) lines, were used for this investigation. Two independent KO lines, generated via the CRISPR-Cas9 system and T-DNA insertion mutagenesis, respectively, showed significantly lower Lpr compared to wild-type rice plants. The decrease in Lpr in the T-DNA KO line was associated with reduced OsPIP2;4 transcript levels, measured by real-time PCR, and lower OsPIP2;4 protein levels, as shown by immunohistochemical analysis. Conversely, no notable increase in Lpr was observed in the Ox lines. These results suggest that OsPIP2;4 is expressed in appropriate tissues in rice roots and is a key factor influencing Lpr. This research represents a significant step toward further understanding the physiological functions of OsPIP2;4 in rice. en-copyright= kn-copyright= en-aut-name=OnishiAya en-aut-sei=Onishi en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HorieTomoaki en-aut-sei=Horie en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshitsukaRyo en-aut-sei=Ishitsuka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasanoShizuka en-aut-sei=Sasano en-aut-mei=Shizuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HorieRie en-aut-sei=Horie en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitoYunosuke en-aut-sei=Mito en-aut-mei=Yunosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UtsugiShigeko en-aut-sei=Utsugi en-aut-mei=Shigeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshikawaJunko en-aut-sei=Ishikawa en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MahdiehMajid en-aut-sei=Mahdieh en-aut-mei=Majid kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University kn-affil= affil-num=6 en-affil=Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University kn-affil= affil-num=7 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=8 en-affil=Institute of Crop Science, NARO kn-affil= affil-num=9 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=10 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=PIP aquaporin kn-keyword=PIP aquaporin en-keyword=Rice kn-keyword=Rice en-keyword=Root hydraulic conductivity kn-keyword=Root hydraulic conductivity en-keyword=Root pressure chamber kn-keyword=Root pressure chamber END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260708 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Streptococcal toxic shock syndrome caused by ST525 Streptococcus dysgalactiae subsp. equisimilis with genomic characterization of virulence and antimicrobial resistance en-subtitle= kn-subtitle= en-abstract= kn-abstract=Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of severe invasive infections. We describe the clinical course of an immunocompromised patient with advanced breast cancer who developed streptococcal toxic shock syndrome, necrotizing fasciitis, and disseminated intramuscular abscesses caused by a multidrug-resistant Lancefield group G SDSE isolate, alongside a comprehensive genomic characterization of its virulence and antimicrobial resistance profiles. Genomic analysis identified the isolate as emm subtype stG840.0 and sequence type 525 (ST525), harboring genes encoding several virulence-associated factors, including an emm-like gene encoding an M-like surface protein, streptokinase, streptolysin O, streptolysin S, and SpeG. Through comprehensive genomic analysis of the highly virulent SDSE isolate, we provided insights into its underlying genetic background. Further accumulation of genomic data is expected to fully elucidate the mechanisms of virulence and antimicrobial resistance in SDSE. en-copyright= kn-copyright= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma 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=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaniokaMaki en-aut-sei=Tanioka en-aut-mei=Maki 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= affil-num=1 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=5 en-affil=Clinical Oncology Center, Okayama University Hospital kn-affil= affil-num=6 en-affil=Research Center for Intestinal Health Science, Okayama University kn-affil= en-keyword=Streptococcus dysgalactiae subsp. equisimilis kn-keyword=Streptococcus dysgalactiae subsp. equisimilis en-keyword=Streptococcal toxic shock syndrome kn-keyword=Streptococcal toxic shock syndrome en-keyword=Necrotizing fasciitis kn-keyword=Necrotizing fasciitis en-keyword=emm typing kn-keyword=emm typing en-keyword=Multilocus sequence typing kn-keyword=Multilocus sequence typing en-keyword=Whole-genome sequencing kn-keyword=Whole-genome sequencing END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=17 article-no= start-page=7542 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260823 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Assessment of the Association of Periodontitis and Diabetes Mellitus with Alzheimerfs Disease in a Mouse Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=The purpose of the present study was to investigate how periodontitis and diabetes mellitus (DM) are associated with Alzheimerfs disease (AD) through microRNA (miRNA) using AD model mice. The experimental period was 8 weeks. Twenty-four male knock-in mice (B6-AppNL-G-F/NL-G-F/J) were divided into four groups: control group fed a normal diet (C), DM group fed a high-fat/sucrose diet (DM), periodontitis (P) group, and DM + periodontitis (DM+P) group. Memory performance was compared using the Y-maze test. Next-generation sequencing was performed on brain samples, and fold changes in miRNA expression were calculated by comparing the DM+P and C groups. Integrated miRNA?mRNA analysis identified putative miRNA-targeted mRNAs, and protein expression of the top candidate gene was assessed. Memory function in the DM+P group was significantly lower than in the C group. Among the seven mRNAs identified by the integrated analysis, Neurod1 showed the greatest decrease in expression, and it was predicted to be regulated by miR-693-3p. Neurod1 protein expression in the hippocampus was significantly lower in the DM+P group than the C group. Our results suggest that the combined exposure to periodontitis and DM was associated with AD-like pathological changes and identified the miR-693-3p/Neurod1 pair as a candidate regulatory axis. en-copyright= kn-copyright= en-aut-name=NakaharaMomoko en-aut-sei=Nakahara en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KataokaKota en-aut-sei=Kataoka en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaruyamaTakayuki en-aut-sei=Maruyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NurhamimMohammad en-aut-sei=Nurhamim en-aut-mei=Mohammad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhangYixuan en-aut-sei=Zhang en-aut-mei=Yixuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuharaDaiki en-aut-sei=Fukuhara en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Uchida-FukuharaYoko en-aut-sei=Uchida-Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IslamMd Monirul en-aut-sei=Islam en-aut-mei=Md Monirul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SaitoTakashi en-aut-sei=Saito en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Division of Dentistry, Medical Development Field, Okayama University kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Dental School, Okayama University kn-affil= affil-num=7 en-affil=Laboratory of Biological Anthropology, Research Center for Integrative Evolutionary Science, The Graduate University for Advanced Studies, SOKENDAI kn-affil= affil-num=8 en-affil=Centre for Policy Studies, University College Cork kn-affil= affil-num=9 en-affil=Department of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health Care kn-affil= affil-num=10 en-affil=Department of Neuropathology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=11 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Alzheimerfs disease kn-keyword=Alzheimerfs disease en-keyword=periodontitis kn-keyword=periodontitis en-keyword=diabetes mellitus kn-keyword=diabetes mellitus en-keyword=microRNA kn-keyword=microRNA en-keyword=mRNA kn-keyword=mRNA END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fenestration Re-creation for Early Fontan Deterioration: Long-Term Hemodynamic and Clinical Outcomes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spontaneous closure of a Fontan fenestration may precipitate early hemodynamic deterioration in vulnerable patients. In such situations, fenestration re-creation may be considered as a rescue strategy when medical therapy is insufficient. However, the long-term hemodynamic consequences of this intervention remain poorly defined. We retrospectively reviewed 62 patients who underwent the Fontan procedure between January 2011 and December 2020 and subsequently experienced spontaneous fenestration closure. Patients were divided into two groups according to management strategy: those who underwent fenestration re-creation (Group 1, n?=?19) and those managed without re-creation (Group 2, n?=?43). Longitudinal hemodynamic data were analyzed using linear mixed models over a median follow-up of 10.2 years. Fenestration closed spontaneously at a median of 12 days (IQR 2.5?26.5) and initial re-creation was performed at the median of 42 days (IQR 11?213) postoperatively. Early and mide-term hemodynamic trends were broadly similar between groups, however, clear divergence emerged in the late follow-up. fenestration re-created patients demonstrated persistently higher central venous pressure and pulmonary vascular resistance, lower systemic vascular resistance, progressive increases in cardiac index, and declining oxygen saturation. Survival in this group remained above 80% during the mid-term follow-up but declined substantially in the late phase compared with patients without re-creation (52% vs. 85%, p?=?0.043). This was accompanied by higher incidences of protein-losing enteropathy/plastic bronchitis, thromboembolism, and severe cyanosis. Fenestration re-creation may provide temporary hemodynamic stabilization in early Fontan deterioration; however, its benefits appear to diminish in the late phase. These findings highlight the need for hemodynamically tailored management strategies and alternative therapeutic options for patients with deteriorating Fontan circulation. en-copyright= kn-copyright= en-aut-name=TranThi Hai Yen en-aut-sei=Tran en-aut-mei=Thi Hai Yen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuritaYoshihiko en-aut-sei=Kurita en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoMaiko en-aut-sei=Kondo en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukushimaYosuke en-aut-sei=Fukushima en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShigemitsuYusuke en-aut-sei=Shigemitsu en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawamotoYuya en-aut-sei=Kawamoto en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaraMayuko en-aut-sei=Hara en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwasakiTatsuo en-aut-sei=Iwasaki en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KasaharaShingo en-aut-sei=Kasahara en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=BabaKenji en-aut-sei=Baba en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Pediatrics, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatric anesthesiology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Cardiovascular Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Fontan operation kn-keyword=Fontan operation en-keyword=Spontaneous fenestration closure kn-keyword=Spontaneous fenestration closure en-keyword=Fenestration recreation kn-keyword=Fenestration recreation en-keyword=Longitudinal hemodynamic changes kn-keyword=Longitudinal hemodynamic changes END start-ver=1.4 cd-journal=joma no-vol=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=31 cd-vols= no-issue=6 article-no= start-page=979 end-page=988 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy of bepotastine compared with hydroxyzine in preventing rituximab-induced infusion-related reactions in non-hodgkin lymphoma patients: a phase II, double-blind, multicenter, and randomized trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background This study evaluated the efficacy of hydroxyzine and bepotastine, first- and second-generation H1 receptor antagonists (H1RA), as pretreatments to prevent infusion-related reactions (IRRs) during the initial rituximab infusion in patients with non-Hodgkin lymphoma.
Methods In this double-blind, multicenter, randomized phase II study, 40 patients received hydroxyzine or bepotastine with acetaminophen 30 min before rituximab infusion. Primary endpoint was incidence of???grade 2 IRRs based on the National Cancer Institute Common Terminology Criteria for Adverse Events. Secondary endpoints included IRRs severity, time to IRR onset, and H1RA-induced drowsiness.
Results Incidence of???grade 2 IRRs was 52.4% and 31.6% for the hydroxyzine (n?=?21) and bepotastine (n?=?19) groups, respectively (P?=?0.184). Distribution of initial and maximum IRR grades in the two groups was not statistically significant (P?=?0.846 and 0.555). Median time (range) to IRR onset in the two groups was 67 (12?112) and 62 (10?119) min, respectively (P?=?0.981). Median visual analog scale score (range and 75th percentile) for drowsiness was 37 (0?100, 46) and 12 (0?100, 29) mm in the two groups, respectively (P?=?0.138). Incidence of???grade 2 IRRs in the absence of bone marrow infiltration was 43.8% and 14.3% in the two groups, respectively (P?=?0.118), and no group differences were observed with bone marrow infiltration.
Conclusions Bepotastine did not show significant superiority over hydroxyzine in preventing rituximab-induced IRRs due to the small sample size. Nevertheless, this exploratory study provides insight for further confirmatory studies.
Trial registration number and date of registration jRCTs051220169; February 14, 2023. en-copyright= kn-copyright= en-aut-name=KitahiroYumi en-aut-sei=Kitahiro en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MinamiHironobu en-aut-sei=Minami en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YakushijinKimikazu en-aut-sei=Yakushijin en-aut-mei=Kimikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurataKeiji en-aut-sei=Kurata en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakaiRina en-aut-sei=Sakai en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaekiMiki en-aut-sei=Saeki en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Okazoe-HirakawaYuri en-aut-sei=Okazoe-Hirakawa en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IidaKotaro en-aut-sei=Iida en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MuraseNatsuko en-aut-sei=Murase en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HarimaIsamu en-aut-sei=Harima en-aut-mei=Isamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KitamuraNaoko en-aut-sei=Kitamura en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ItoharaKotaro en-aut-sei=Itohara en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OmuraTomohiro en-aut-sei=Omura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SugimotoTakeshi en-aut-sei=Sugimoto en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakakuraHidetomo en-aut-sei=Takakura en-aut-mei=Hidetomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KitaoAkihito en-aut-sei=Kitao en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TakahashiMasako en-aut-sei=Takahashi en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShimoyamaManabu en-aut-sei=Shimoyama en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OkunoMamoru en-aut-sei=Okuno en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YanoIkuko en-aut-sei=Yano en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=2 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=5 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=6 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=7 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=8 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=9 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=10 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=11 en-affil=Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=13 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=14 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Kita-Harima Medical Center kn-affil= affil-num=16 en-affil=Department of Hematology and Oncology, Kita-Harima Medical Center kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Kita-Harima Medical Center kn-affil= affil-num=18 en-affil=Department of Pharmacy, Kita-Harima Medical Center kn-affil= affil-num=19 en-affil=Department of Hematology and Oncology, Kohnan Medical Center kn-affil= affil-num=20 en-affil=Department of Pharmacy, Kohnan Medical Center kn-affil= affil-num=21 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= en-keyword=Rituximab kn-keyword=Rituximab en-keyword=Infusion-related reactions kn-keyword=Infusion-related reactions en-keyword=Non-Hodgkin lymphoma kn-keyword=Non-Hodgkin lymphoma en-keyword=Bepotastine kn-keyword=Bepotastine en-keyword=Hydroxyzine kn-keyword=Hydroxyzine en-keyword=Drowsiness kn-keyword=Drowsiness END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=19 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260403 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Potential effects of intradialytic exercise therapy on physical performance in hemodialysis patients based on the intervention period: a systematic review and meta-analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Intradialytic exercise during hemodialysis (HD) improves physical function and shows high adherence. In Japan, the 2018 guideline by the Japanese Society of Renal Rehabilitation supports intradialytic exercise, but medical insurance only covers the first 90 days. As new studies have emerged since the guideline was published, we conducted a systematic review and meta-analysis to evaluate the impact and optimal duration of exercise interventions beyond 12 weeks.
Methods We followed a preregistered protocol (PROSPERO CRD42025642273) and PRISMA-P guidelines. Randomized controlled trials of adult patients undergoing HD performing structured exercise were identified via MEDLINE database (PubMed, March 2017?November 2024) and ICHUSHI-Web database. Two independent reviewers screened studies, extracted data, and assessed risk of bias using Cochrane RoB 2.0. Outcomes included peak oxygen uptake (VO2peak), maximal oxygen uptake (VO2max), 6 min walk distance, timed up and go (TUG) test, handgrip strength, sit-to-stand (STS) performance, and biochemical measures (hemoglobin, standard weekly urea Kt/V [std Kt/V]). Pooled mean differences (MD) with 95% confidence intervals (CI) were calculated using a mixed-effects model (Hartung?Knapp?Sidik?Jonkman method).
Results A total of 71 studies, including 43 newly identified studies, were included. Risk of bias was moderate-to-high. Interventions?>?12 weeks significantly improved 6 min walking distance (MD 52.4 m [95% CI 35.4?69.3], p??12 weeks of exercise.
Conclusions Our findings suggest that exercise interventions lasting more than 12 weeks can enhance physical performance. Nevertheless, the applicability of these results to older patients remains uncertain, as most evidence is derived from middle-aged cohorts.
Trial registration Registered in the PROSPERO database (CRD42025642273). en-copyright= kn-copyright= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HondaYu en-aut-sei=Honda en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KojimaShigeki en-aut-sei=Kojima en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakeHiromasa en-aut-sei=Miyake en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimotoMasatoshi en-aut-sei=Nishimoto en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HishikawaAkihito en-aut-sei=Hishikawa en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TonomuraShun en-aut-sei=Tonomura en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SofueTadashi en-aut-sei=Sofue en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiNaohiko en-aut-sei=Fujii en-aut-mei=Naohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SaitohMasakazu en-aut-sei=Saitoh en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NaritaIchiei en-aut-sei=Narita en-aut-mei=Ichiei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamagataKunihiro en-aut-sei=Yamagata en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HoshinoJunichi en-aut-sei=Hoshino en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawarazakiHiroo en-aut-sei=Kawarazaki en-aut-mei=Hiroo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SakuradaTsutomu en-aut-sei=Sakurada en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Internal Medicine, Teikyo University Hospital Mizonokuchi kn-affil= affil-num=2 en-affil=Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine kn-affil= affil-num=3 en-affil=Kojima Kidney and Dialysis Clinic kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Nara Medical University kn-affil= affil-num=6 en-affil=Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine kn-affil= affil-num=8 en-affil=Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Department of Nephrology, Hyogo Prefectural Nishinomiya Hospital kn-affil= affil-num=10 en-affil=Department of Physical Therapy, Faculty of Health Science, Juntendo University kn-affil= affil-num=11 en-affil=Niigata Institute for Health and Sports Medicine, Niigata Sports Association kn-affil= affil-num=12 en-affil=Department of Nephrology, Institute of Medicine, University of Tsukuba kn-affil= affil-num=13 en-affil=Division of Preventive and Sports Nephrology, Graduate School of Comprehensive Human Sciences, Tokyo Womenfs Medical University kn-affil= affil-num=14 en-affil=Department of Internal Medicine, Teikyo University Hospital Mizonokuchi kn-affil= affil-num=15 en-affil=Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine kn-affil= en-keyword=Intradialytic exercise kn-keyword=Intradialytic exercise en-keyword=Physical performance kn-keyword=Physical performance en-keyword=Exercise period kn-keyword=Exercise period en-keyword=Short physical performance battery kn-keyword=Short physical performance battery en-keyword=Handgrip strength kn-keyword=Handgrip strength en-keyword=Systematic review kn-keyword=Systematic review en-keyword=Meta-analysis kn-keyword=Meta-analysis END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=13 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260308 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Duration-stratified effects of exercise therapy on health-related quality of life in hemodialysis patients: a systematic review and meta-analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Patients on maintenance hemodialysis (HD) have reduced health-related quality of life (HRQoL). Structured exercise therapy is recommended, but domain-specific effects and the influence of intervention duration remain uncertain. This study evaluated the impact of structured exercise therapy on multiple HRQoL domains, including fatigue and depression, stratified by intervention duration.
Methods: We conducted a systematic review and meta-analysis, searching MEDLINE (PubMed) through November 2024. The protocol was registered in PROSPERO (CRD42025642273). We included trials comparing structured exercise with non-exercise controls in adult HD patients. Primary outcomes were Short Form (SF)-36 Physical and Mental Component Summaries (PCS, MCS), fatigue, pain, general health, and depression (Beck Depression Inventory). Data were synthesized using random-effects models, stratified by intervention duration (??3 versus?>?3 months). Risk of bias was assessed using the Cochrane RoB 2 tool.
Results: We identified 94 randomized controlled trials (5228 participants); 22 reported HRQoL outcomes and were meta-analyzed. Exercise significantly improved fatigue (mean difference [MD]?+?7.27, 95% confidence interval [CI] 4.75?9.80) and reduced depressive symptoms in?>?3-month trials (MD??7.62, 95% CI??8.34 to??6.90); no???3-month depression data were available. In overall analyses, general health (MD?+?11.59, 95% CI 6.98?16.21) and PCS (MD?+?5.83, 95% CI 0.71?10.94) improved, whereas MCS (MD?+?7.60, 95% CI??3.75 to 18.94) and pain (MD?+?2.19, 95% CI??4.41 to 8.79) showed no clear benefit. Short-term interventions (??3 months) yielded significant improvements in pain and general health. In longer-term interventions (>?3 months), general health estimates were similar in magnitude but statistically nonsignificant, and pain effects were also nonsignificant with substantial heterogeneity. Fatigue improved in both duration strata.
Conclusions: Structured exercise therapy appears to improve fatigue in patients on maintenance HD and may provide additional gains in PCS and general health with interventions longer than 3 months. Improvements in depressive symptoms were observed from limited evidence, and duration-specific effects remain uncertain because no trials assessed depression at???3 months. Effects on pain and MCS remain uncertain owing to substantial heterogeneity. Larger long-term trials are needed to clarify the sustainability of HRQoL benefits beyond 3 months. en-copyright= kn-copyright= en-aut-name=HondaYu en-aut-sei=Honda en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KojimaShigeki en-aut-sei=Kojima en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakeHiromasa en-aut-sei=Miyake en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimotoMasatoshi en-aut-sei=Nishimoto en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HishikawaAkihito en-aut-sei=Hishikawa en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TonomuraShun en-aut-sei=Tonomura en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SofueTadashi en-aut-sei=Sofue en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiNaohiko en-aut-sei=Fujii en-aut-mei=Naohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SaitohMasakazu en-aut-sei=Saitoh en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NaritaIchiei en-aut-sei=Narita en-aut-mei=Ichiei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamagataKunihiro en-aut-sei=Yamagata en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HoshinoJunichi en-aut-sei=Hoshino en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawarazakiHiroo en-aut-sei=Kawarazaki en-aut-mei=Hiroo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SakuradaTsutomu en-aut-sei=Sakurada en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Teikyo University Hospital Mizonokuchi kn-affil= affil-num=3 en-affil=Kojima Kidney and Dialysis Clinic kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Nara Medical University kn-affil= affil-num=6 en-affil=Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine kn-affil= affil-num=8 en-affil=Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Department of Nephrology, Hyogo Prefectural Nishinomiya Hospital kn-affil= affil-num=10 en-affil=Department of Physical Therapy, Faculty of Health Science, Juntendo University kn-affil= affil-num=11 en-affil=Niigata Institute for Health and Sports Medicine, Niigata Sports Association kn-affil= affil-num=12 en-affil=Department of Nephrology, Institute of Medicine, University of Tsukuba kn-affil= affil-num=13 en-affil=Department of Nephrology, Tokyo Womenfs 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=31 cd-vols= no-issue=5 article-no= start-page=e70145 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260821 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Transforming Life Science Through Chromosome]Level Genome Assemblies en-subtitle= kn-subtitle= en-abstract= kn-abstract=Advances in long-read sequencing and Hi?C scaffolding have made chromosome-level genome assembly increasingly accessible to individual laboratories, shifting genome research from large consortium-led projects toward investigator-driven studies across diverse taxa. This transition allows researchers to select organisms based on biological questions rather than the prior availability of genomic resources. In this review, we summarize the core experimental and computational steps for generating, evaluating, and annotating chromosome-level assemblies, and examine how they have advanced research in non-model organisms and genetically complex systems. Representative case studies illustrate four major contributions: resolving structural variation and lineage-specific genome architecture, linking genome organization to phenotypic innovation and plasticity, reconstructing deep chromosome evolution and macrosynteny, and distinguishing homologous and homoeologous chromosomes in polyploid genomes. These examples show that chromosome-level assemblies provide more than complete reference sequences. They establish a continuous genomic coordinate system through which genes, regulatory elements, transposable element insertions, sequence variants, and cellular states can be interpreted within broader chromosomal, population, and evolutionary contexts. We describe this integrative perspective as gglocal biology.h Future progress will require pangenomic, population-scale, and haplotype-resolved resources integrated with multi-omics and functional analyses. Collectively, chromosome-level genomics is reshaping life science by embedding molecular functions within chromosomal and evolutionary contexts. en-copyright= kn-copyright= en-aut-name=KonTetsuo en-aut-sei=Kon en-aut-mei=Tetsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KataokaKosuke en-aut-sei=Kataoka en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LuoYi]Jyun en-aut-sei=Luo en-aut-mei=Yi]Jyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WibisanaJohannes Nicolaus en-aut-sei=Wibisana en-aut-mei=Johannes Nicolaus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TogaKouhei en-aut-sei=Toga en-aut-mei=Kouhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UnoNarumi en-aut-sei=Uno en-aut-mei=Narumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MondenYuki en-aut-sei=Monden en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HamadaMayuko en-aut-sei=Hamada en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Neurosciences and Developmental Biology, University of Vienna kn-affil= affil-num=2 en-affil=Graduate School of Engineering, Tokyo University of Agriculture and Technology kn-affil= affil-num=3 en-affil=Biodiversity Research Center, Academia Sinica kn-affil= affil-num=4 en-affil=Genomics and Regulatory Systems Unit, Okinawa Institute of Science and Technology Graduate University kn-affil= affil-num=5 en-affil=Laboratory of BioDX, PtBio Co]Creation Research Center, Genome Editing Innovation Center, Hiroshima University kn-affil= affil-num=6 en-affil=Laboratory of Bioengineering, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=8 en-affil=Ushimado Marine Institute, Okayama University kn-affil= en-keyword=chromosome-level genome assembly kn-keyword=chromosome-level genome assembly en-keyword=genome evolution kn-keyword=genome evolution en-keyword=Hi?C scaffolding kn-keyword=Hi?C scaffolding en-keyword=long-read sequencing kn-keyword=long-read sequencing en-keyword=non-model animals kn-keyword=non-model animals END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=12 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260707 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Knockout analysis of period and timeless and EGFP-based visualization of per-expressing clock cells in the cricket circadian clock en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the present study, we generated crickets with knockout of either period (per) or timeless (tim) gene by CRISPR/Cas9-based genome editing. We also identified a naturally occurring per- mutant lacking a large coding region including PAS domains. To examine possible synergistic effects, a per- and timKO double mutant was generated by applying genome editing to the per- crickets. Under constant darkness (DD), timKO crickets exhibited a locomotor rhythm with a free-running period of 23.06?}?0.20?h (mean?}?SD), which was significantly shorter than that of the parental strain (23.78?}?0.12?h). By contrast, perKO and per- crickets showed basically similar phenotype of locomotor rhythm: they exhibited an arrhythmic pattern during the first two to three weeks after transfer to DD but subsequently showed a complex rhythmic pattern with one or multiple components with significantly longer free-running periods (33.35?}?10.72?h). In the per-;timKO double mutants, approximately 60% of individuals became arrhythmic, while the remaining 40% exhibited complex rhythms with extremely longer free-running periods (37.0?}?9.17?h) under DD. These results suggest the existence of an underlying oscillatory mechanism that is responsible for regulating locomotor rhythms independently of the canonical per/tim feedback loop. Furthermore, we generated a reporter line on a per? background by knocking egfp into exon 1 of the per gene, allowing egfp expression to report per transcription. EGFP expression was detected in three distinct clusters of cells within the optic lobe: two located along the dorsal and ventral boundaries between the lamina and medulla neuropils, and one situated near the accessory medulla. These findings raise the possibility that these form part of the circadian clock network that governs circadian locomotor rhythms. en-copyright= kn-copyright= en-aut-name=TomiokaKenji en-aut-sei=Tomioka en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueShintaro en-aut-sei=Inoue en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitoTaro en-aut-sei=Mito en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriyamaYoshiyuki en-aut-sei=Moriyama en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshiiTaishi en-aut-sei=Yoshii en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Bio-Innovation Research Center, Tokushima University kn-affil= affil-num=3 en-affil=Bio-Innovation Research Center, Tokushima University kn-affil= affil-num=4 en-affil=Department of Natural Sciences, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Circadian clock kn-keyword=Circadian clock en-keyword=Cricket kn-keyword=Cricket en-keyword=Genome editing kn-keyword=Genome editing en-keyword=Locomotor rhythm kn-keyword=Locomotor rhythm en-keyword=period kn-keyword=period en-keyword=per-less oscillation kn-keyword=per-less oscillation en-keyword=timeless kn-keyword=timeless END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260819 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Micro-segregation of Primary Si in ADC14 (Al?17Si?4Cu) Alloy Produced by Unidirectional Continuous Casting en-subtitle= kn-subtitle= en-abstract= kn-abstract=An upgrading approach for hypereutectic Al?Si alloys was investigated through controlled segregation of Si using a unidirectional casting process. The precipitation behavior and spatial distribution of primary Si in the hypereutectic ADC14 (Al?17Si?4Cu) alloy were systematically examined at different casting speeds (0.06, 1.9, and 10 mm/s). Microstructural observations revealed that high casting speed suppresses primary Si formation due to rapid solidification, whereas intermediate speed leads to a relatively uniform distribution of primary Si. In contrast, low casting speed combined with a holding period for 2 min promotes pronounced segregation and coarsening of primary Si in localized regions. Energy-dispersive X-ray spectroscopy analysis confirmed significant fluctuations in Si concentration along the casting direction, particularly after process interruption. Based on these results, a preliminary upgrading process was proposed, involving the selective removal of Si-enriched regions followed by remelting. This approach resulted in a reduction of Si content to approximately 13.9 wt.%, corresponding to a decrease of about 3%. The results demonstrate that controlling solidification behavior to induce phase separation provides a promising and energy-efficient strategy for upgrading recycled Al?Si alloys. en-copyright= kn-copyright= en-aut-name=TakeuchiShuhei en-aut-sei=Takeuchi en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakagawaShota en-aut-sei=Nakagawa en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShinzatoYoshifumi en-aut-sei=Shinzato en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MinodaTadashi en-aut-sei=Minoda en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtsukaNaotaka en-aut-sei=Ohtsuka en-aut-mei=Naotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkayasuMitsuhiro en-aut-sei=Okayasu en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=UACJ Corporation kn-affil= affil-num=3 en-affil=UACJ Corporation kn-affil= affil-num=4 en-affil=UACJ Corporation kn-affil= affil-num=5 en-affil=UACJ Corporation kn-affil= affil-num=6 en-affil=Department of Mechanical and Systems Engineering, Okayama University kn-affil= en-keyword=upgrading technique kn-keyword=upgrading technique en-keyword=Al?Si alloy kn-keyword=Al?Si alloy en-keyword=primary Si kn-keyword=primary Si en-keyword=segregation kn-keyword=segregation en-keyword=unidirectional solidification kn-keyword=unidirectional solidification END start-ver=1.4 cd-journal=joma no-vol=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=43 cd-vols= no-issue=11 article-no= start-page=1302 end-page=1313 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trastuzumab-Pertuzumab Plus Eribulin or Taxane as First-Line Chemotherapy for Human Epidermal Growth Factor 2?Positive Locally Advanced/Metastatic Breast Cancer: The Randomized Noninferiority Phase III EMERALD Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Trastuzumab-pertuzumab (HP) plus taxane is a current standard first-line therapy for recurrent or metastatic human epidermal growth factor 2 (HER2)+ breast cancer (BC). We investigated noninferiority of eribulin to a taxane when combined with dual HER2 blockade as first-line systemic treatment for locally advanced/metastatic HER2+ BC.
Methods In the phase III EMERALD trial (target sample size, 480; ClinicalTrials.gov identifier: NCT03264547/UMIN000027938), patients were randomly assigned (1:1) to receive eribulin 1.4 mg/m2 once daily on days 1 and 8 (eribulin group) or a taxane (docetaxel 75 mg/m2 once on day 1 or paclitaxel 80 mg/m2 once daily on days 1, 8, and 15; taxane group) intravenously in a 21-day cycle, each with HP on day 1. The primary end point was progression-free survival (PFS; intention-to-treat population). Secondary end points included objective response rate, overall survival (OS), patient-reported quality of life (QoL), and safety. Noninferiority was tested using the stratified Cox proportional hazards model to estimate hazard ratios (HRs) for PFS events, with a noninferiority HR margin of 1.33.
Results Between August 2017 and June 2021, 446 patients (median age, 56.0 years) were enrolled. The median PFS was 14.0 and 12.9 months in the eribulin group (n = 224) and taxane group (n = 222 [docetaxel/paclitaxel, n = 186/36]), respectively (HR, 0.95 [95% CI, 0.76 to 1.19]), which confirmed the noninferiority of the study regimen. The median OS was 65.3 months in the taxane group but has not been reached in the eribulin group. Median time to QoL deterioration was numerically longer with eribulin than with taxane. Adverse event (AE) rates were similar, despite the longer duration of eribulin use. Infusion reaction, skin-related AEs, diarrhea, and edema were more common with taxane, whereas neutropenia was more common with eribulin.
Conclusion The results suggested that eribulin + HP is an option for first-line treatment of locally advanced/metastatic HER2+ BC. en-copyright= kn-copyright= en-aut-name=YamashitaToshinari en-aut-sei=Yamashita en-aut-mei=Toshinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SajiShigehira en-aut-sei=Saji en-aut-mei=Shigehira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakanoToshimi en-aut-sei=Takano en-aut-mei=Toshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaitoYoichi en-aut-sei=Naito en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuneizumiMichiko en-aut-sei=Tsuneizumi en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshimuraAkiyo en-aut-sei=Yoshimura en-aut-mei=Akiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiMasato en-aut-sei=Takahashi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsurutaniJunji en-aut-sei=Tsurutani en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwataniTsuguo en-aut-sei=Iwatani en-aut-mei=Tsuguo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitadaMasahiro en-aut-sei=Kitada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TadaHiroshi en-aut-sei=Tada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoriNatsuko en-aut-sei=Mori en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HiguchiToru en-aut-sei=Higuchi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwasaTsutomu en-aut-sei=Iwasa en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ArakiKazuhiro en-aut-sei=Araki en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KoizumiKei en-aut-sei=Koizumi en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HasegawaHiroki en-aut-sei=Hasegawa en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UchidaYohei en-aut-sei=Uchida en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MoritaSatoshi en-aut-sei=Morita en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MasudaNorikazu en-aut-sei=Masuda en-aut-mei=Norikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Breast Surgery and Oncology, Kanagawa Cancer Center kn-affil= affil-num=2 en-affil=Department of Medical Oncology, Fukushima Medical University kn-affil= affil-num=3 en-affil=Department of Breast Medical Oncology, The Cancer Institute Hospital of JFCR kn-affil= affil-num=4 en-affil=Department of General Internal Medicine, National Cancer Center Hospital East kn-affil= affil-num=5 en-affil=Department of Breast Surgery, Shizuoka General Hospital kn-affil= affil-num=6 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=7 en-affil=Department of Breast Surgery, Hokkaido University Hospital kn-affil= affil-num=8 en-affil=Advanced Cancer Translational Research Institute, Showa University kn-affil= affil-num=9 en-affil=Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Breast Disease Center, Asahikawa Medical University Hospital kn-affil= affil-num=11 en-affil=Department of Surgery, Division of Breast and Endocrine Surgery, Tohoku University Hospital kn-affil= affil-num=12 en-affil=Department of Breast Surgery, Seirei Hamamatsu General Hospital kn-affil= affil-num=13 en-affil=Department of Breast Unit, Japanese Red Cross Saitama Hospital kn-affil= affil-num=14 en-affil=Department of Medical Oncology, Kindai University Hospital kn-affil= affil-num=15 en-affil=Department of Breast Medical Oncology, Gunma Prefectural Cancer Center kn-affil= affil-num=16 en-affil=Department of Surgery 1, Division of Breast Surgery, Hamamatsu University School of Medicine kn-affil= affil-num=17 en-affil=Medical HQs, Eisai Co, Ltd kn-affil= affil-num=18 en-affil=Medical HQs, Eisai Co, Ltd kn-affil= affil-num=19 en-affil=Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University kn-affil= affil-num=20 en-affil=Department of Breast Surgery, Graduate School of Medicine, Kyoto University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=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 ƒÀ-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 ƒÀ-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=62 cd-vols= no-issue=7 article-no= start-page=1352 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=Diabetes Burden in the Middle East and North Africa Region, 1990?2023: An Ecological Time-Trend Analysis of GBD Estimates en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Objectives: The Middle East and North Africa (MENA) region has one of the highest age-standardized diabetes prevalence rates globally, yet all-age, diabetes-specific evidence incorporating GBD 2023 estimates through 2023 remains limited. Materials and Methods: Using Global Burden of Disease (GBD) 2023 estimates for 21 MENA countries from 1990 to 2023, this ecological time-trend analysis quantified 33-year trends in incidence, prevalence, mortality, and disability-adjusted life-years (DALYs); compared pre-2019 and post-2019 trajectories using joinpoint regression; characterized age- and sex-specific burden patterns; and quantified contributions of modifiable risk factors. Results: Age-standardized incidence increased 92%, from 251.7 (95% uncertainty interval [UI]: 231.5 to 272.4) to 482.5 (95% UI: 451.5 to 516.4) per 100,000, and prevalence more than doubled, from 5564 (95% UI: 5088 to 6024) to 11,247 (95% UI: 10,382 to 12,132) per 100,000. In 2023, males exhibited higher DALY rates than females in most adult age groups from age 15 years onward, shifting away from the female-predominant pattern seen in 1990; female rates remained higher at several of the oldest age groups. Children aged 0 to 14 years were the only group with declining DALY rates (?52% to ?57%). Post-2019 incidence was higher in 15 of 21 countries, and six countries had higher DALY trends with non-overlapping confidence intervals. Because we only have four to five years of data, these short trends are preliminary and require care when evaluating. High body-mass index was the leading modifiable risk factor. Conclusions: These data support country-specific prevention and chronic-care strategies across the MENA region. 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=HigashionnaTsukasa en-aut-sei=Higashionna en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=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=Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=6 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=7 en-affil=Faculty of Pharmacy, Haiphong University of Medicine and Pharmacy 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 Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=GBD 2023 kn-keyword=GBD 2023 en-keyword=diabetes mellitus kn-keyword=diabetes mellitus en-keyword=Middle East and North Africa kn-keyword=Middle East and North Africa en-keyword=joinpoint regression kn-keyword=joinpoint regression en-keyword=cardiovascular risk factors kn-keyword=cardiovascular risk factors en-keyword=epidemiology kn-keyword=epidemiology en-keyword=public health kn-keyword=public health END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260820 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Performance of generative artificial intelligence in oral and maxillofacial radiology based on the board-certification examination of Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective To evaluate the performance and potential utility of generative artificial intelligence (AI) in oral and maxillofacial radiology using the board-certification examination administered by the Japanese Society for Oral and Maxillofacial Radiology (JSOMR).
Methods The responses generated by ChatGPT for multiple-choice questions from the board-certification examination of the JSOMR over the three-year period from 2020 to 2022 were assessed. The questions were manually entered individually as prompts for GPT-3.5, GPT-4, and GPT-5, which are the models available from ChatGPT. The accuracy was calculated according to examination year, question format, and level of taxonomy.
Results GPT-3.5 achieved an accuracy of 40.3% for the three years (42.9%, 42.0%, and 36.0% for 2020, 2021, and 2022, respectively), that of GPT-4 was 67.8% (67.3%, 74.0%, and 62.0%, respectively), and that of GPT-5 was 76.5% (79.6%, 78.0%, and 72.0%, respectively). GPT-5fs results exceeded the passing score for each year with the accuracy significantly outperformed that of GPT-3.5 and GPT-4. Regarding performance according to the question format, GPT-5 performed significantly superior to the earlier models, especially on two-answer questions.
Conclusions On the board-certification examination of the JSOMR, the performance of GPT-5 was significantly superior to that of GPT-3.5 and GPT-4. This suggests that, given the rapid development of generative AI, GPT-5 has reached a level of text-based knowledge equivalent to that assessed in the board-certification examination of the JSOMR. en-copyright= kn-copyright= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawazuToshiyuki en-aut-sei=Kawazu en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HisatomiMiki en-aut-sei=Hisatomi en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujikuraMamiko en-aut-sei=Fujikura en-aut-mei=Mamiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkadaShunsuke en-aut-sei=Okada en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShibanumaAkira en-aut-sei=Shibanuma en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NambaYuri en-aut-sei=Namba en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaSuzuka en-aut-sei=Yoshida en-aut-mei=Suzuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshidaSaori en-aut-sei=Yoshida en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakamuraYoshihide en-aut-sei=Nakamura en-aut-mei=Yoshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YanagiYoshinobu en-aut-sei=Yanagi en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Medical Development Field, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Radiology, Medical Development Field, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Radiology, Medical Development Field, Okayama University kn-affil= affil-num=6 en-affil=Department of Community and Global Health, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Radiology, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Radiology, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=9 en-affil=Preliminary Examination Room, Medical Development Field, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Artificial intelligence kn-keyword=Artificial intelligence en-keyword=Generative artificial intelligence kn-keyword=Generative artificial intelligence en-keyword=ChatGPT kn-keyword=ChatGPT en-keyword=Large language model kn-keyword=Large language model en-keyword=Radiology kn-keyword=Radiology en-keyword=Education kn-keyword=Education END start-ver=1.4 cd-journal=joma no-vol=131 cd-vols= no-issue=8 article-no= start-page=e2025JB033593 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=Effect of Fluorine on the Stability of Dense Hydrous Mg Silicates With Implications for the Deep Water Cycle en-subtitle= kn-subtitle= en-abstract= kn-abstract=Water is believed to be transported, at least locally, into the Earth's deep mantle via hydrous minerals. Fluorine not only tends to interact with water but also influences the stability of hydrous minerals. Thus, knowledge of its stability could be important in understanding the deep-water cycle. In this study, we conducted high-pressure experiments to investigate the stability of dense hydrous Mg silicates in the presence of fluorine at pressures ranging from 9 to 23 GPa. In the presence of even small amounts of fluorine, clinohumite or phase E survives up to approximately 17 GPa, allowing it to exist without dehydration at temperatures by about 200‹C higher than a fluorine-free system. At pressures above 18 GPa, superhydrous phase B stabilizes as a major fluorine host. Fluorine partitions very little into phase D, leaving its stability field unchanged, but the stability field of superhydrous phase B extends to temperatures above 1400‹C, thereby enabling the hydrous phase in the dragged wedge mantle just above the slab to have transport potential into the lower mantle. en-copyright= kn-copyright= en-aut-name=YoshinoTakashi en-aut-sei=Yoshino en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiaoYunfan en-aut-sei=Miao en-aut-mei=Yunfan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SajiSatheesh T. en-aut-sei=Saji en-aut-mei=Satheesh T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IkutaDaijo en-aut-sei=Ikuta en-aut-mei=Daijo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HeXuejing en-aut-sei=He en-aut-mei=Xuejing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OtaTsutomu en-aut-sei=Ota en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KunihiroTakuya en-aut-sei=Kunihiro en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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 Planetary Materials, Okayama University kn-affil= affil-num=4 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=5 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=6 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=7 en-affil=Geochemical Research Center Graduate School of Science, The University of Tokyo 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= en-keyword=dense hydrous Mg silicates kn-keyword=dense hydrous Mg silicates en-keyword=fluorine kn-keyword=fluorine en-keyword=water kn-keyword=water en-keyword=transition zone kn-keyword=transition zone en-keyword=superhydrous phase B kn-keyword=superhydrous phase B en-keyword=phase relation kn-keyword=phase relation END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=4 article-no= start-page=241 end-page=246 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Video-Assisted Thoracoscopic Resection of an Upper Mediastinal Ectopic Parathyroid Adenoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Primary hyperparathyroidism (pHPT) is typically caused by a parathyroid adenoma, although some cases arise from ectopic glands. Accurate preoperative localization is essential for guiding surgical strategy, particularly for mediastinal lesions. We report successful video-assisted thoracoscopic surgery (VATS) for an upper mediastinal parathyroid adenoma. A 68-year-old woman was referred for hypercalcemia during evaluation for recurrent ureteral stones. Laboratory tests revealed elevated serum calcium (13.2 mg/dl) and intact parathyroid hormone (iPTH) levels (266 pg/ml). Contrast-enhanced computed tomography, magnetic resonance imaging, and 99mTc-methoxyisobutylisonitrile scintigraphy identified a 20-mm mass adjacent to the right esophageal wall. VATS was performed due to the tumorfs mediastinal location. The lesion was resected with intraoperative nerve monitoring (IONM) to avoid recurrent laryngeal nerve damage. Postoperatively, iPTH and calcium levels rapidly normalized. Transient hypocalcemia and mild hoarseness occurred but resolved with calcium supplementation and conservative management. Pathological examination confirmed a parathyroid adenoma without malignancy. VATS offers a safe and minimally invasive approach for upper mediastinal parathyroid adenomas. IONM and vigilant calcium management are crucial for minimizing these complications. This case highlights the importance of comprehensive imaging, surgical planning, and postoperative care in managing upper mediastinal pHPT. en-copyright= kn-copyright= en-aut-name=HasegawaYuta en-aut-sei=Hasegawa en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujimotoHironori en-aut-sei=Tsujimoto en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UehataNaoyuki en-aut-sei=Uehata en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KariyaRisa en-aut-sei=Kariya en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IdeAsuma en-aut-sei=Ide en-aut-mei=Asuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiTakafumi en-aut-sei=Suzuki en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujishimaSeiichiro en-aut-sei=Fujishima en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KouzuKeita en-aut-sei=Kouzu en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YaguchiYoshihisa en-aut-sei=Yaguchi en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyaiKosuke en-aut-sei=Miyai en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KuriharaAyumu en-aut-sei=Kurihara en-aut-mei=Ayumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OgataSho en-aut-sei=Ogata en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsukumaSusumu en-aut-sei=Matsukuma en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UenoHideki en-aut-sei=Ueno en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=4 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=6 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= affil-num=10 en-affil=Department of Laboratory Medicine, National Defense Medical College Hospital kn-affil= affil-num=11 en-affil=Department of Laboratory Medicine, National Defense Medical College Hospital kn-affil= affil-num=12 en-affil=Department of Laboratory Medicine, National Defense Medical College Hospital kn-affil= affil-num=13 en-affil=Department of Laboratory Medicine, National Defense Medical College Hospital kn-affil= affil-num=14 en-affil=Department of Surgery, National Defense Medical College Hospital kn-affil= en-keyword=primary hyperparathyroidism kn-keyword=primary hyperparathyroidism en-keyword=parathyroid neoplasm kn-keyword=parathyroid neoplasm en-keyword=ectopic tissue kn-keyword=ectopic tissue en-keyword=video-assisted thoracoscopic surgery kn-keyword=video-assisted thoracoscopic surgery END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=8 article-no= start-page=e114802 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260819 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Incidence and Time to Onset of Pseudophakic Cystoid Macular Edema (Irvine-Gass Syndrome) After 1,325 Consecutive Cataract Surgeries Performed by a Single Surgeon Over Four Years en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives
Macular edema after cataract surgery is known as pseudophakic cystoid macular edema or Irvine-Gass syndrome. The aim of this study was to determine the incidence and time to onset of cystoid macular edema after uncomplicated cataract surgery.
Methods
A retrospective review was conducted of 1,325 consecutive cataract surgeries performed by a single surgeon at a single institution over four years, from January 2022 to December 2025.
Results
Among 1,325 eyes, one or more macular cysts were detected by optical coherence tomography in 27 eyes (2.0%) of 22 patients who complained of blurred vision or decreased visual acuity after having no symptoms immediately after surgery. The 22 patients (27 eyes: 12 right and 15 left) comprised 12 men and 10 women. Their ages at the time of surgery ranged from 57 to 82 years, with a median of 75.5 years. Of the 27 eyes that developed macular cysts, 13 eyes with no preoperative or intraoperative risk factors for inflammation received topical 0.1% bromfenac twice daily as the only postoperative anti-inflammatory treatment, together with topical antibacterial 0.5% moxifloxacin four times daily. In contrast, the remaining 14 eyes, which had risk factors for inflammation, such as exfoliation, floppy iris, poor mydriasis, extracapsular cataract extraction, or diabetes mellitus, received topical bromfenac twice daily and 0.1% betamethasone (or 0.1% fluorometholone in two eyes) four times daily, as well as topical moxifloxacin. The time from surgery to the diagnosis of macular cysts ranged from one week to eight months, with a median of two weeks, in the 13 eyes treated with topical bromfenac only. In the 14 eyes treated with the combination of topical bromfenac and betamethasone, the time to diagnosis ranged from two weeks to 13 months, with a median of two months. In 26 of the 27 eyes, the macular cysts disappeared and visual acuity returned to normal without residual symptoms within two weeks to seven months, with a median of one month, after topical betamethasone four times daily was initiated or resumed.
Conclusions
Pseudophakic macular cysts developed during the postoperative course in eyes with no preoperative or intraoperative risk factors that received topical bromfenac alone. They also developed later in the postoperative course after the combination of topical bromfenac and betamethasone was discontinued in eyes with risk factors for inflammation. The macular cysts disappeared following the initiation or resumption of topical betamethasone, accompanied by recovery of visual acuity and resolution of symptoms. 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= en-aut-name=Nakago-MatsuoChie en-aut-sei=Nakago-Matsuo en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=2 en-affil=Orthodontics, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=betamethasone kn-keyword=betamethasone en-keyword=bromfenac kn-keyword=bromfenac en-keyword=irvine-gass syndrome kn-keyword=irvine-gass syndrome en-keyword=macular cyst kn-keyword=macular cyst en-keyword=moxifloxacin kn-keyword=moxifloxacin en-keyword=optical coherence tomography kn-keyword=optical coherence tomography en-keyword=pseudophakic cystoid macular edema kn-keyword=pseudophakic cystoid macular edema en-keyword=single surgeon kn-keyword=single surgeon en-keyword=small-incision cataract surgery kn-keyword=small-incision cataract surgery en-keyword=topical medication kn-keyword=topical medication 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 Japanfs 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 providersf 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=D?ezOrland en-aut-sei=D?ez en-aut-mei=Orland kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Dom?nguez-ValentinMev en-aut-sei=Dom?nguez-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=Fjeldv?rMagnhild K en-aut-sei=Fjeldv?r 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=G?mez Garc?aEncarna B en-aut-sei=G?mez Garc?a 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=L?pez-Fern?ndezAdri? en-aut-sei=L?pez-Fern?ndez en-aut-mei=Adri? kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=MachackovaEva en-aut-sei=Machackova en-aut-mei=Eva kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=MartinsAlexandra en-aut-sei=Martins en-aut-mei=Alexandra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=MensenkampArjen R en-aut-sei=Mensenkamp en-aut-mei=Arjen R kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=MomozawaYukihide en-aut-sei=Momozawa en-aut-mei=Yukihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=MontalbanGemma en-aut-sei=Montalban en-aut-mei=Gemma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=MonteiroAlvaro N A en-aut-sei=Monteiro en-aut-mei=Alvaro N A kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=NevanlinnaHeli en-aut-sei=Nevanlinna en-aut-mei=Heli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=NgeowJoanne en-aut-sei=Ngeow en-aut-mei=Joanne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=PalmeroEdenir Inez en-aut-sei=Palmero en-aut-mei=Edenir Inez kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=PedersenInge Sokilde en-aut-sei=Pedersen en-aut-mei=Inge Sokilde kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=QueFrances Victoria F en-aut-sei=Que en-aut-mei=Frances Victoria F kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=Santamari?aMarta en-aut-sei=Santamari?a en-aut-mei=Marta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=Santana dos SantosElizabeth en-aut-sei=Santana dos Santos en-aut-mei=Elizabeth kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=SingerChristian F en-aut-sei=Singer en-aut-mei=Christian F kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=Sio?ekMonika en-aut-sei=Sio?ek en-aut-mei=Monika kn-aut-name= 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=D?partement de M?decine 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. Lukefs Medical Center kn-affil= affil-num=13 en-affil=Hospital Cl?nico San Carlos, Molecular Oncology Laboratory, Instituto de Investigaci?n Sanitaria del Hospital Cl?nico San Carlos kn-affil= affil-num=14 en-affil=Department of Genetics, Institut Curie kn-affil= affil-num=15 en-affil=Vall dfHebron Hospital Universitari, Area of Clinical and Molecular Genetics, Vall dfHebron 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, Sk?ne 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. Lukefs Medical Center kn-affil= affil-num=21 en-affil=Fundaci?n P?blica Galega de Medicina Xen?mica and Instituto de Investigaci?n 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. Lukefs 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 dfHebron Barcelona Hospital Campus, Vall dfHebron 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. Lukefs Medical Center kn-affil= affil-num=49 en-affil=Fundaci?n P?blica Galega de Medicina Xen?mica and Instituto de Investigaci?n 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 Educaci?n M?dica e Investigaciones Cl?nicas "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=Fundaci?n P?blica Galega de Medicina Xen?mica and Instituto de Investigaci?n Sanitaria de Santiago de Compostela kn-affil= affil-num=64 en-affil=Instituto de Biolog?a y Gen?tica Molecular, Splicing and Genetic Susceptibility to Cancer, Consejo Superior de Investigaciones Cient?ficas - 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=44 cd-vols= no-issue=1 article-no= start-page=552 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260810 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Preoperative membranous urethral length predicts quality-of-life recovery and urinary incontinence after holmium enucleation of the prostate en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Holmium laser enucleation of the prostate (HoLEP) relieves bladder outlet obstruction, but postoperative quality-of-life (QOL) recovery and stress urinary incontinence (SUI) differ among patients. We evaluated whether preoperative membranous urethral length (MUL) on MRI predicts QOL recovery and SUI after HoLEP, independent of clinical and surgical factors.
Methods This single-center retrospective study included 135 patients with preoperative MRI. MUL was measured on sagittal T2-weighted images. The primary outcome was 6-month International Prostate Symptom Score (IPSS) -QOL ? 1. SUI was defined as the use of ?1 pad per day at 6 months. IPSS-QOL changes were analyzed with generalized estimating equations. For 6-month QOL recovery and SUI, logistic regression was adjusted for age, enucleated weight, prostate volume, baseline QOL, and surgeon. We evaluated thickness of posterior wall of membranous urethral sphincter (TPWMUS), membranous urethral volume (MUV), and a short-MUL/thin-TPWMUS phenotype.
Results The 6-month IPSS-QOL ? 1 rate was 40.0%; SUI occurred in 19/135 patients (14.1%). Longer MUL was linked to better QOL recovery at every time point (p ? 0.015) and independently predicted both 6-month QOL recovery (adjusted odds ratio [aOR] 1.35, 95% CI 1.14?1.61) and lower SUI risk (odds ratio [OR] 0.76, 0.61?0.93), remaining significant after adjustment. Adding MUL improved prediction (AUC for SUI 0.588¨0.704; for QOL 0.716¨0.760). Across MUL tertiles, QOL recovery rose from 13.9% to 56.1% ,and SUI fell from 20.0% to 2.2%. Short MUL/thin-TPWMUS showed higher SUI and poorer QOL recovery.
Conclusions Preoperative MUL on MRI independently predicted QOL recovery and continence after HoLEP. en-copyright= kn-copyright= en-aut-name=NagasakiNaoya en-aut-sei=Nagasaki en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeTomofumi en-aut-sei=Watanabe en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanemotoShin en-aut-sei=Kanemoto en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WatanabeToyohiko en-aut-sei=Watanabe en-aut-mei=Toyohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Holmium laser enucleation of the prostate kn-keyword=Holmium laser enucleation of the prostate en-keyword=Membranous urethral length kn-keyword=Membranous urethral length en-keyword=Magnetic resonance imaging kn-keyword=Magnetic resonance imaging en-keyword=Stress urinary incontinence kn-keyword=Stress urinary incontinence en-keyword=Quality of life kn-keyword=Quality of life en-keyword=Benign prostatic hyperplasia kn-keyword=Benign prostatic hyperplasia END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=8 article-no= start-page=e70553 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=Burden of Lower Urinary Tract and Genital Symptoms in Young Transgender Men: Prevalence and Impact on Daily Life en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To investigate the prevalence of lower urinary tract symptoms (LUTS) and genital symptoms among transgender men in Japan, and to evaluate their impact on daily life, including limitations resulting from concerns about toilet accessibility.
Methods: We conducted a cross-sectional, single-center survey of assigned-female-at-birth individuals aged 16?years or older who had been approved for gender-affirming hormone therapy at our gender center. A self-administered questionnaire included the Core Lower Urinary Tract Symptom Score (CLSS), vaginal and urethral symptom items, toilet use outside the home, preferences regarding male urinals, and activity restriction related to toilet access. Data were analyzed descriptively, and multivariable logistic regression analyses were performed.
Results: Data from 322 participants (median age 33?years) were analyzed. Overall, 80% reported at least one LUTS, 46% reported at least one bothersome symptom, and 14% had a CLSS global quality-of-life (QOL) score of ??4. Vaginal symptoms occurred in 13% of participants, and 2% reported post-micturition leakage. Most participants (62%) did not use male urinals but wished to use them. Activity restriction due to toilet-related concerns, defined as avoiding or limiting activities such as travel, shopping, or going to the cinema, was reported by 20%, and higher total CLSS was associated with both activity restriction and poor urinary-related QOL.
Conclusions: LUTS and genital symptoms are common in young transgender men, and greater LUTS burden is linked to urinary-related QOL impairment and toilet-related activity restriction. These findings highlight the need for targeted clinical care and improved accessibility of public toilets for transgender men. en-copyright= kn-copyright= en-aut-name=KobayashiTomoko en-aut-sei=Kobayashi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OzakiNariaki en-aut-sei=Ozaki en-aut-mei=Nariaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HoriiSatoshi en-aut-sei=Horii en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshinagaKasumi en-aut-sei=Yoshinaga en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamanoiTomoaki en-aut-sei=Yamanoi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=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=MatsumotoYuko en-aut-sei=Matsumoto en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=InoueMiyabi en-aut-sei=Inoue en-aut-mei=Miyabi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IshiiAyano en-aut-sei=Ishii en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=WatanabeToyohiko en-aut-sei=Watanabe en-aut-mei=Toyohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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 Hospital kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Urology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Urology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Miyakekai Good-Life Hospital kn-affil= affil-num=16 en-affil=Miyabi Urogyne Clinic Okayama Japan kn-affil= affil-num=17 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Urology, Okayama University Hospital kn-affil= affil-num=19 en-affil=Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=20 en-affil=Department of Urology, Okayama University Hospital kn-affil= en-keyword=lower urinary tract symptoms kn-keyword=lower urinary tract symptoms en-keyword=transgender men kn-keyword=transgender men en-keyword=urinary-related activity restriction kn-keyword=urinary-related activity restriction en-keyword=vaginal symptoms kn-keyword=vaginal symptoms END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=7 article-no= start-page=e72982 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202607 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Biologically Dominant Trophoblastic Component Guiding Neoadjuvant EMA/CO in Endometrial Carcinoma: A Clinical Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Endometrial carcinoma with choriocarcinomatous components (ECCC) is a rare and aggressive malignancy for which optimal management remains undefined. We report a case illustrating how preoperative identification of a biologically dominant trophoblastic component can guide treatment sequencing and achieve durable remission. A 61-year-old postmenopausal woman presented with abnormal uterine bleeding. Endometrial biopsy revealed a mixed tumor composed predominantly of choriocarcinomatous elements with a minor grade 1 endometrioid carcinoma component. Despite only superficial myometrial invasion, imaging demonstrated multiple pulmonary nodules, and serum human chorionic gonadotropin (hCG) was markedly elevated (46,538?mIU/mL). This clinicopathological incongruity suggested that the trophoblastic component, rather than the low-grade endometrioid carcinoma, was driving disease progression. Neoadjuvant EMA/CO chemotherapy was therefore prioritized to achieve rapid systemic control. After six cycles, serum hCG normalized and pulmonary lesions completely resolved. The patient subsequently underwent total hysterectomy and bilateral salpingo-oophorectomy, which revealed no residual choriocarcinoma. She remains disease-free more than two years after completion of treatment. This case highlights the importance of recognizing clinicopathological incongruity and identifying the biologically dominant tumor component when determining treatment sequencing in rare mixed malignancies. en-copyright= kn-copyright= en-aut-name=ShirakawaShinsuke en-aut-sei=Shirakawa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaYui en-aut-sei=Tanaka en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujikawaAtsushi en-aut-sei=Fujikawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImataniRyoko en-aut-sei=Imatani en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TaniokaMomoko en-aut-sei=Tanioka en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TaniYoshinori en-aut-sei=Tani en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiharaHanako en-aut-sei=Sugihara en-aut-mei=Hanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkamotoKazuhiro en-aut-sei=Okamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IdaNaoyuki en-aut-sei=Ida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsuokaHirofumi en-aut-sei=Matsuoka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HaragaJunko en-aut-sei=Haraga en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OgawaChikako en-aut-sei=Ogawa en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Diagnostic Pathology, Okayama University kn-affil= affil-num=16 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=choriocarcinoma kn-keyword=choriocarcinoma en-keyword=EMA/CO kn-keyword=EMA/CO en-keyword=endometrial cancer kn-keyword=endometrial cancer en-keyword=endometrioid carcinoma kn-keyword=endometrioid carcinoma END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=5 article-no= start-page=764 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260227 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The New Era of Intraperitoneal Carboplatin in Ovarian Cancer: From Biological Rationale to Clinical Implementation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Epithelial ovarian cancer is predominantly characterized by peritoneal dissemination, providing a strong biological rationale for intraperitoneal (IP) chemotherapy. Although IP cisplatin-based regimens have demonstrated substantial survival benefits in pivotal randomized trials, toxicity and catheter-related complications limit their widespread adoption. IP carboplatin has emerged as a pragmatic alternative with improved tolerability while preserving its pharmacokinetic advantages. This review summarizes the biological and pharmacological rationale for IP carboplatin and critically examines the clinical evidence, with a particular emphasis on the Intraperitoneal Carboplatin for Ovarian Cancer (iPocc) trial and its divergence from Gynecologic Oncology Group (GOG)-252. We further discuss the potential applicability of IP carboplatin beyond the traditional setting of minimal residual disease, including patients undergoing neoadjuvant chemotherapy and interval debulking surgery, as well as its possible use in the contemporary era of maintenance therapy. Collectively, the accumulated evidence supports renewed consideration of IP carboplatin as a versatile component in modern ovarian cancer management. en-copyright= kn-copyright= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujikawaAtsushi en-aut-sei=Fujikawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaYui en-aut-sei=Tanaka en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniokaMomoko en-aut-sei=Tanioka en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImataniRyoko en-aut-sei=Imatani en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TaniYoshinori en-aut-sei=Tani en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugiharaHanako en-aut-sei=Sugihara en-aut-mei=Hanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoKazuhiro en-aut-sei=Okamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuokaHirofumi en-aut-sei=Matsuoka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IdaNaoyuki en-aut-sei=Ida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HaragaJunko en-aut-sei=Haraga en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OgawaChikako en-aut-sei=Ogawa en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=ovarian cancer kn-keyword=ovarian cancer en-keyword=intraperitoneal chemotherapy kn-keyword=intraperitoneal chemotherapy en-keyword=carboplatin kn-keyword=carboplatin en-keyword=dose-dense TC therapy kn-keyword=dose-dense TC therapy en-keyword=homologous recombination deficiency kn-keyword=homologous recombination deficiency en-keyword=PARP inhibitor kn-keyword=PARP inhibitor en-keyword=neoadjuvant chemotherapy kn-keyword=neoadjuvant chemotherapy END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=1 article-no= start-page=e0340963 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260113 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fertility-sparing surgery with neoadjuvant chemotherapy in early and locally advanced cervical cancer: A clinical protocol en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fertility preservation remains a critical concern in young women with early or locally advanced cervical cancer, as standard radical treatments compromise reproductive potential. This study aims to evaluate the feasibility, oncological safety, and reproductive outcomes of fertility-sparing treatment involving neoadjuvant chemotherapy followed by cervical conization and laparoscopic pelvic lymphadenectomy. This single-center, prospective, open-label, single-arm, Phase II interventional study will assess patients with FIGO stage IB2?IB3 cervical cancer (FIGO stage 2018) desiring fertility preservation. Eligible patients will receive three cycles of dose-dense paclitaxel and carboplatin (dd-TC), followed by conization and laparoscopic lymphadenectomy. The primary endpoint is successful uterine preservation. Patients requiring concurrent chemoradiotherapy due to inadequate treatment response will not be considered successful. Secondary endpoints include 2-year recurrence-free survival (RFS), overall survival (OS), quality of life assessments, menstrual and ovulatory resumption, pregnancy, live birth, miscarriage, and preterm birth. Adverse events will be graded according to CTCAE v5.0. en-copyright= kn-copyright= en-aut-name=TaniokaMomoko en-aut-sei=Tanioka en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IdaNaoyuki en-aut-sei=Ida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaYui en-aut-sei=Tanaka en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujikawaAtsushi en-aut-sei=Fujikawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ImataniRyoko en-aut-sei=Imatani en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TaniYoshinori en-aut-sei=Tani en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiharaHanako en-aut-sei=Sugihara en-aut-mei=Hanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkamotoKazuhiro en-aut-sei=Okamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuokaHirofumi en-aut-sei=Matsuoka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HaragaJunko en-aut-sei=Haraga en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OgawaChikako en-aut-sei=Ogawa en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=8 article-no= start-page=e0356180 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Study protocol: Effect of inulin supplementation on gut microbiota in patients with oral lichen planus ? A double-blind, randomised, placebo-controlled parallel-group trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oral lichen planus is a chronic inflammatory disease of the oral mucosa characterised by immune dysregulation, but its pathogenesis remains incompletely understood and no curative treatment has been established. Our previous work showed that patients with oral lichen planus exhibit gut dysbiosis, including reduced microbial diversity and depletion of butyrate-producing bacteria. Because butyrate promotes regulatory T-cell differentiation and supports immune homeostasis, targeting this dysbiosis may represent a microbiota-directed approach for immune modulation in oral lichen planus. This study aims to investigate the effects of inulin supplementation on the gut microbiota and related immune markers in patients with oral lichen planus. This multicentre, double-blind, randomised, placebo-controlled parallel-group trial will enrol 80 patients with oral lichen planus. Participants will be randomly assigned in a 1:1 ratio to receive either inulin (8 g/day) or a maltose placebo for 4 weeks, in addition to standard care. The primary outcome is the change in the relative abundance of prespecified butyrate-producing gut bacteria from baseline to the end of intervention at Week 6. Secondary outcomes include changes in gut microbiota diversity, salivary microbiota composition, faecal short-chain fatty acid concentrations, peripheral blood regulatory T-cell counts, blood test parameters, and clinical symptoms of oral lichen planus. Analyses will follow the intention-to-treat principle, and between-group differences will be assessed using appropriate statistical methods. This trial is designed to evaluate, in a randomised placebo-controlled setting, whether a microbiota-directed intervention can modify gut microbial profiles and related immune markers in patients with oral lichen planus. The findings are expected to clarify whether inulin supplementation can modify gut microbial profiles and related immunological markers in patients with oral lichen planus. Trial registration: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000060840, registered on 1 April 2026 (https://rctportal.mhlw.go.jp/detail/um?trial_id=UMIN000060840#). en-copyright= kn-copyright= en-aut-name=NambuKoki en-aut-sei=Nambu en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanekoNaoki en-aut-sei=Kaneko en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokomizoShiho en-aut-sei=Yokomizo en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChenHu en-aut-sei=Chen en-aut-mei=Hu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanLijing en-aut-sei=Yan en-aut-mei=Lijing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShiyaoWang en-aut-sei=Shiyao en-aut-mei=Wang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShizumaRyusei en-aut-sei=Shizuma en-aut-mei=Ryusei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwataEiji en-aut-sei=Iwata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhyamaYukiko en-aut-sei=Ohyama en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkagawaShohei en-aut-sei=Akagawa en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawanoShintaro en-aut-sei=Kawano en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MoriyamaMasafumi en-aut-sei=Moriyama en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=2 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=3 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=4 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=5 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=6 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=7 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=10 en-affil=Department of Pediatrics, Kansai Medical University kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=13 en-affil=Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=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 glonger dinner-to-bed time" (>120 minutes), gshorter dinner-to-bed time" (?120 minutes or less), and girregular dinner-to-bed time.h 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=2 article-no= start-page=e79063 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Short-Term and Long-Term Outcomes of Robotic Gastrectomy for Gastric Cancer: A Single-Center, Single-Arm Prospective Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Robotic gastrectomy (RG) has emerged as a promising approach for gastric cancer (GC) treatment, offering advantages such as enhanced dexterity, improved visualization, and increased precision. However, its widespread adoption remains limited due to technical complexity, high costs, limited applications, and insufficient evidence.
Methods: We conducted a single-center, prospective study to evaluate the safety and feasibility of RG, including robotic total gastrectomy (RTG), robotic proximal gastrectomy (RPG), and robotic distal gastrectomy (RDG) with D1+ or D2 lymphadenectomy, in clinical stage I/II GC. The primary endpoint was the incidence of intraoperative and postoperative complications, while the secondary endpoints included surgical outcomes and long-term prognosis.
Results: Seven patients were enrolled. No intraoperative complications or conversions to open surgery occurred. The primary endpoint was met, with no major postoperative complications. RTG had a longer operative time and more lymph nodes dissected than RDG and RPG. The median postoperative hospital stay was 10 days. Recurrence was observed in two cases, one of which achieved long-term survival without chemotherapy.
Conclusion: Our findings demonstrate the safety and feasibility of RG for early and advanced GC. Further multicenter studies with larger cohorts are needed to establish its oncological benefits and cost-effectiveness, facilitating broader clinical adoption. en-copyright= kn-copyright= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KakiutchiYoshihiko en-aut-sei=Kakiutchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KashimaHajime en-aut-sei=Kashima en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishizakiMasahiko en-aut-sei=Nishizaki en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=gastric cancer kn-keyword=gastric cancer en-keyword=long-term outcome kn-keyword=long-term outcome en-keyword=prospective study kn-keyword=prospective study en-keyword=robotic gastrectomy kn-keyword=robotic gastrectomy en-keyword=short-term outcome kn-keyword=short-term outcome END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=2 article-no= start-page=e79001 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250214 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Durable Response to Nivolumab Combined With Metformin in Advanced Pancreatic Cancer: A Case Report With Seven Years of Follow-Up en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a case of poorly differentiated pancreatic cancer that showed an exceptional response to combination therapy with nivolumab and metformin. A 58-year-old man presented with epigastric pain and was diagnosed with locally advanced pancreatic cancer with para-aortic lymph node metastasis. After disease progression following modified FOLFIRINOX therapy (a combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin), the patient was enrolled in a phase Ib clinical trial of nivolumab (3 mg/kg biweekly) combined with metformin (750 mg/day). Post-treatment imaging showed marked tumor shrinkage with normalization of the tumor markers. During treatment, the patient was diagnosed with early-stage lung cancer and underwent successful left S1+S2 segmentectomy with temporary suspension of immunotherapy. The therapeutic response of pancreatic cancer has been sustained for seven years, with minimal residual disease. This unprecedented response duration is particularly noteworthy considering his microsatellite stability, which typically predicts a limited response to immune checkpoint inhibition.
This case demonstrates an exceptional response to nivolumab and metformin combination therapy in poorly differentiated pancreatic cancer. The remarkable durability of the response suggests the need for further investigation to identify patients most likely to benefit from this therapeutic approach. en-copyright= kn-copyright= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoHironari en-aut-sei=Kato en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KozukiToshiyuki en-aut-sei=Kozuki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University kn-affil= affil-num=8 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=immune checkpoint inhibitors kn-keyword=immune checkpoint inhibitors en-keyword=immunotherapy kn-keyword=immunotherapy en-keyword=metformin kn-keyword=metformin en-keyword=nivolumab kn-keyword=nivolumab en-keyword=pancreatic cancer kn-keyword=pancreatic cancer END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=3 article-no= start-page=e80184 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cholecystectomy Is Linked to Worse Clinical Outcomes in Primary Sclerosing Cholangitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent findings have suggested that gallbladder-derived retinoic acid signaling plays a crucial role in the regeneration of damaged intrahepatic biliary ducts. This retrospective cohort study analyzed the clinical records of 20 patients with primary sclerosing cholangitis (PSC) treated at our hospital between 2013 and 2024. We investigated the clinical implications of gallbladder removal in patients with PSC, a progressive cholangiopathy with limited therapeutic options. We retrospectively analyzed the data of patients with PSC and compared patients with and without prior cholecystectomy to assess the impact on disease progression using the Mayo risk score, Fibrosis-4 (FIB4) index, and other clinical parameters. Our findings indicated that cholecystectomy was associated with worse Mayo risk scores (p = 0.0004) and an elevated FIB4 index (p = 0.021), suggesting a potential link between gallbladder removal and accelerated disease progression. Furthermore, mortality and transplant-free survival analysis revealed significantly worse outcomes in the cholecystectomy group (odds ratio = 21.0, p = 0.032). However, given the retrospective nature and small sample size of this study, selection bias cannot be excluded, and further research is needed to confirm these findings. These findings support the hypothesis that gallbladder-derived factors, such as retinoic acid, may influence PSC progression and highlight the need for further research into therapeutic interventions targeting this pathway. en-copyright= kn-copyright= en-aut-name=MiyakeNozomi en-aut-sei=Miyake en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YasugiKengo en-aut-sei=Yasugi en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University kn-affil= en-keyword=biliary diseases kn-keyword=biliary diseases en-keyword=cholecystectomy kn-keyword=cholecystectomy en-keyword=gall bladder kn-keyword=gall bladder en-keyword=liver function kn-keyword=liver function en-keyword=post cholecystectomy kn-keyword=post cholecystectomy en-keyword=primary sclerosing cholangitis (psc) kn-keyword=primary sclerosing cholangitis (psc) END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=2 article-no= start-page=e78399 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Rare Course of Chiari Malformation With Large Syringomyelia Presenting at 54 Years Old en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chiari malformation type 1 (CM1) is considered a congenital condition. The symptoms include severe headache, hypalgesia, and loss of temperature sensation. It constitutes a significant burden among children and young adults. The onset of symptoms of CM1 is more commonly observed in relatively young children and is very rare in those over 50 years old. This study aims to present a rare surgical case of CM1 associated with a large syringomyelia in a 54-year-old man.
A 54-year-old man with low back pain was introduced to our department. He had slight hyperreflexia of the extremities, slight muscle weakness in both legs, and numbness in the right leg (3/10). He also had urinary and bowel incontinence and spastic gait. Cervical magnetic resonance imaging (MRI) showed CM1 with large syringomyelia extending from C1 to T11. The cervical canal was widened because of a long history of spinal cord expansion.
The patient was successfully treated surgically by foramen magnum decompression and syringosubarachnoid shunting under the guidance of O-arm navigation. The muscle weakness and sensory function recovered almost entirely on the one-year follow-up. The patient's cervical Japanese Orthopedic Association (JOA) score had improved from 11/17 to 16/17.
Gradually enlarging syringomyelia with slight CM1 is rare, but surgeons should consider this condition's possibility. Foramen magnum decompression achieves good results even in cases with a long history of syringomyelia. This new navigation technique provides an excellent result for a large syringomyelia with CM1. en-copyright= kn-copyright= en-aut-name=TanakaMasato en-aut-sei=Tanaka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SharmaSneha en-aut-sei=Sharma en-aut-mei=Sneha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GoriKushal H en-aut-sei=Gori en-aut-mei=Kushal H kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShohidullahMd en-aut-sei=Shohidullah en-aut-mei=Md kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Orthopedics, North Delhi Municipal Corporation (DMC) Medical College kn-affil= affil-num=3 en-affil=Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=4 en-affil=Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=5 en-affil=Orthopedic Surgery, Okayama University Hospital kn-affil= en-keyword=chiari malformation kn-keyword=chiari malformation en-keyword=foramen magnum decompression kn-keyword=foramen magnum decompression en-keyword=large syringomyelia kn-keyword=large syringomyelia en-keyword=navigation system kn-keyword=navigation system en-keyword=syringosubarachnoid shunting kn-keyword=syringosubarachnoid shunting END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=8 article-no= start-page=e66070 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240803 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Navigation-Guided C-arm-Free Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Comparative Study of Cage Orientation and Screw Insertion Accuracy Against the Conventional C-arm-Assisted Technique en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is a widely utilized technique in spine surgery. This study compares the efficacy and safety of MIS-TLIF performed with traditional C-arm fluoroscopy and C-arm-free O-arm navigation. To the best of our knowledge, our study is the first to compare cage positioning between C-arm-free and C-arm techniques for MIS- TLIF.
Methods: A retrospective, comparative analysis was conducted on 43 patients undergoing MIS-TLIF. The group was divided based on the utilization of C-arm fluoroscopy or C-arm-free O-arm navigation. Key parameters analyzed included cage orientation, screw insertion accuracy, operative efficiency, and postoperative recovery. Radiographic measurements were used to assess surgical precision and perioperative complications were documented.
Results: The study encompassed 43 patients, with no significant differences in demographic characteristics between the two groups. Surgical time and blood loss were comparable between C-arm-free and C-arm groups. O-arm navigation significantly reduced pedicle screw misplacement (p=0.024). Cage positioning differed between groups (p=0.0063): O-arm cages were mostly mid-center, while C-arm cages were more anterior-center. Such differences in the cage location did not cause any impact on clinical outcome. No significant differences were observed in postoperative complications (screw loosenings, dural tears, surgical site infections) between groups. The Oswestry Disability Index scores at the final follow-up showed no significant difference between the O-arm and C-arm groups, indicating similar levels of postoperative disability.
Conclusion: Despite the clinically insignificant difference in cage placement between C-arm-free and C-arm dependent, C-arm-free MIS-TLIF significantly improves screw placement accuracy and reduces radiation exposure to operating stuff. This suggests its potential as a valuable tool for safer and more precise spinal fusion surgery. 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=TanakaMasato en-aut-sei=Tanaka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KumawatChetan en-aut-sei=Kumawat en-aut-mei=Chetan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GunjotikarSharvari en-aut-sei=Gunjotikar en-aut-mei=Sharvari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 ORCID= en-aut-name=KomatsubaraTadashi en-aut-sei=Komatsubara en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AratakiShinya en-aut-sei=Arataki en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Navigation-Guided C-arm-Free Minimally Invasive Transforaminal kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=5 en-affil=Navigation-Guided C-arm-Free Minimally Invasive Transforaminal kn-affil= affil-num=6 en-affil=Navigation-Guided C-arm-Free Minimally Invasive Transforaminal kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=navigation kn-keyword=navigation en-keyword=o-arm kn-keyword=o-arm en-keyword=c-arm free kn-keyword=c-arm free en-keyword=mis-tlif kn-keyword=mis-tlif en-keyword=spine surgery kn-keyword=spine surgery END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=8 article-no= start-page=e66069 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240803 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A New Minimally Invasive Technique for Thoracolumbar/Lumbar Focal Kyphosis Due to Osteoporotic Vertebral Fracture: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteoporotic vertebral fractures are common fractures in the elderly population and are often associated with low back pain and disruption in daily living activities. Reconstruction surgeries, such as corpectomy, are among the treatment options for these conditions. However, a corpectomy requires a longer surgical procedure and involves a significant amount of blood loss. We present the case of an 80-year-old woman with severe low back pain due to an L2 fracture and focal kyphosis treated with a novel minimally invasive technique. The patient underwent anterior and posterior surgery in the right decubitus position using a C-arm-free technique. Hyperlordotic cages were inserted in the upper and lower disc space via a lateral approach, while percutaneous pedicle screws were inserted from a posterior approach. These procedures were performed simultaneously under navigation guidance only. en-copyright= kn-copyright= en-aut-name=TanakaMasato en-aut-sei=Tanaka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Al AskarAbd El Kader en-aut-sei=Al Askar en-aut-mei=Abd El Kader kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KumawatChetan en-aut-sei=Kumawat en-aut-mei=Chetan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EkadeShashank J en-aut-sei=Ekade en-aut-mei=Shashank J kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= en-keyword=oblique lumbar interbody fusion kn-keyword=oblique lumbar interbody fusion en-keyword=novel technique kn-keyword=novel technique en-keyword=c-arm free kn-keyword=c-arm free en-keyword=thoracolumbar focal kyphosis kn-keyword=thoracolumbar focal kyphosis en-keyword=osteoporotic vertebral fractures kn-keyword=osteoporotic vertebral fractures END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=10 article-no= start-page=e71325 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vonoprazan-Associated Mucosal Redness: A Report of Two Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vonoprazan, a potassium-competitive acid blocker, is effective at treating acid-related gastrointestinal disorders but has been linked to gastric mucosal redness, a novel condition. This report describes two cases of vonoprazan-associated mucosal redness. Case 1 involved a 73-year-old woman who developed longitudinal erythema and mild mucosal changes after starting vonoprazan seven years ago. Case 2 involved a 70-year-old man who exhibited significant erythema and atrophic gastritis after seven months of treatment. In both cases, the pathological findings included hemorrhage in the superficial mucosa, highlighting that microhemorrhage may be the corresponding pathological finding for vonoprazan-associated mucosal redness. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkedaNobumasa en-aut-sei=Ikeda en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Pathology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Internal Medicine, Clinic Ikeda kn-affil= en-keyword=endoscopy kn-keyword=endoscopy en-keyword=gastric mucosal redness kn-keyword=gastric mucosal redness en-keyword=microhemorrhage kn-keyword=microhemorrhage en-keyword=potassium-competitive acid blocker kn-keyword=potassium-competitive acid blocker en-keyword=vonoprazan kn-keyword=vonoprazan END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=3 article-no= start-page=e81104 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Pemafibrate and Eicosapentaenoic Acid Ethyl Ester on Endothelial Function in Patients With Hypertriglyceridemia and Coronary Artery Disease: A Study Protocol for a Multicenter, Open-Label Randomised Controlled Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Despite intensive low-density lipoprotein cholesterol-lowering therapies effectively reducing cardiovascular events, residual cardiovascular risks remain significant, with hypertriglyceridemia being an important contributing factor. Pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, has shown strong triglyceride-lowering effects and potential vascular benefits. Similarly, eicosapentaenoic acid ethyl ester (EPA) has demonstrated cardiovascular protective effects, particularly in patients with hypertriglyceridemia. However, the comparative impact of these agents on endothelial function, a key marker of atherosclerotic progression, has not been thoroughly evaluated in patients with coronary artery disease (CAD). The PRIME (PRospective comparIson of peMafibrate and Eicosapentaenoic acid ethyl ester on vascular functions for hypertriglyceridemia) trial is a multi-center, open-label, randomised trial designed to compare the effects of pemafibrate and EPA on endothelial function in patients with CAD and hypertriglyceridemia. Patients receiving statin therapy with fasting triglyceride levels ?150 mg/dL will be randomised into two groups: pemafibrate (0.2 mg/day, with possible dose escalation to 0.4 mg/day) or EPA (1800 mg/day, with possible dose escalation to 2700 mg/day). Endothelial function will be assessed with reactive hyperemia index (RHI). The primary endpoint is the change in RHI at 12 weeks. The secondary endpoints include the changes in RHI at 24 weeks, correlations between changes in RHI and changes in lipid biomarkers, and changes in biochemical parameters at 12 and 24 weeks. This study investigates the comparative effects of pemafibrate and EPA on endothelial function, addressing an unmet need in managing residual cardiovascular risk in patients with CAD. The findings will contribute to the optimisation of treatment strategies in patients with CAD and hypertriglyceridemia. en-copyright= kn-copyright= en-aut-name=MiyoshiTrou en-aut-sei=Miyoshi en-aut-mei=Trou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuzawaYasushi en-aut-sei=Matsuzawa en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DoiMasayuki en-aut-sei=Doi en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugiyamaSeigo en-aut-sei=Sugiyama en-aut-mei=Seigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Cardiovascular Medicine, Okayama University kn-affil= affil-num=2 en-affil=Cardiovascular Medicine, Kumamoto University kn-affil= affil-num=3 en-affil=Cardiology, Kagawa Prefectural Central Hospital kn-affil= affil-num=4 en-affil=Cardiovascular Medicine, Okayama University kn-affil= affil-num=5 en-affil=Cardiovascular Medicine, Jinnouchi Hospital kn-affil= en-keyword=cardiovascular risk kn-keyword=cardiovascular risk en-keyword=eicosapentaenoic acid kn-keyword=eicosapentaenoic acid en-keyword=endothelial function kn-keyword=endothelial function en-keyword=pemafibrate kn-keyword=pemafibrate en-keyword=triglyceride kn-keyword=triglyceride END start-ver=1.4 cd-journal=joma no-vol=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=16 cd-vols= no-issue=9 article-no= start-page=e70066 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Decreased CD3+CD56+ Natural Killer T Lymphocytes and Increased Human Leukocyte Antigen-DR+ Cells in the Inflamed Area of Pouchitis in Ulcerative Colitis Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Pouchitis is an inflammatory condition that affects the ileal pouch during ileal pouch-anal anastomosis surgery. Despite its clinical significance, precise immunological mechanisms underlying pouchitis remain unclear. This study aimed to investigate the lymphocyte profile in the ileal pouch of patients with pouchitis compared to those with familial adenomatous polyposis (FAP) and ulcerative colitis without pouchitis using flow cytometry and immunohistochemical techniques.
Methods: We prospectively analyzed endoscopic biopsy specimens from the ileal pouches of 15 patients and categorized them into three groups: FAP, ulcerative colitis with an inflammation-free pouch (UC-I), and ulcerative colitis with ulcers and/or erosions in the pouch (UC-UE). Flow cytometry was used to assess various T-lymphocyte markers, including cluster of differentiation (CD) 4, CD8, CD56, and human leukocyte antigen (HLA)-DR. Immunohistochemistry was performed to visualize the spatial distribution of CD3+, CD56+, and HLA-DR+ cells in the pouch mucosa.
Results: We observed significantly reduced CD56+/CD3+ and CD8+/CD3+ ratios in the UC-UE group compared to those in the FAP group, indicating a disruption in natural killer T-cell populations. Immunohistochemical analysis revealed that the spatial distribution of lymphocytes differed among the non-inflamed mucosa, dense lymphocyte infiltration, and lymphoid follicles, with these components frequently intermingling. CD56 + cells were less abundant in areas with dense lymphocyte infiltration, whereas HLA-DR+ cells were more abundant.
Conclusion: Our study revealed a decrease in CD56+ natural killer T cells and an increase in HLA-DR+-activated T cells in areas with dense lymphocyte infiltration, suggesting an association between these cells and pouchitis in ulcerative colitis. The distinct patterns observed in non-inflamed mucosa, areas with dense lymphocyte infiltration, and lymphoid follicles underscore the need for further analyses of these three segments to elucidate the immunological mechanisms underlying pouchitis. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakaharaMasahiro en-aut-sei=Takahara en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InokuchiToshihiro en-aut-sei=Inokuchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=flow cytometry kn-keyword=flow cytometry en-keyword=immunohistochemistry kn-keyword=immunohistochemistry en-keyword=lymphocytes, pouchitis kn-keyword=lymphocytes, pouchitis en-keyword=ulcerative colitis kn-keyword=ulcerative colitis END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=11 article-no= start-page=e74176 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Accuracy of Cup Alignment in Total Hip Arthroplasty: A Comparison Between Portable Navigation and Goniometer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Navigation systems, including portable navigation systems, used for total hip arthroplasty (THA) are useful for achieving higher cup alignment accuracy. NAVBIT, a newly available portable navigation system, uses a unique registration method, the table tilt registration. However, its accuracy is unclear. This retrospective study aimed to investigate whether THA with a portable navigation system in the lateral position with the flip technique is more accurate than THA with a cup goniometer in the supine or lateral positions.
Methodology This study included 96 consecutive patients (77 women, 19 men) who underwent primary cementless THA using either a portable navigation system in the lateral position with the flip technique or a cup goniometer in the supine or lateral positions. The average age of the patients was 66.8 years (range = 29-91) and the average body mass index was 24.6 kg/m2 (range = 17.5-39.9). The accuracy of cup orientation was compared among the three groups.
Results The absolute values of the difference in cup inclination and anteversion with the NAVBIT (2.1 } 1.7‹, 2.0 } 1.4‹) were smaller than that with the cup goniometer in the supine (3.4 } 2.4‹, 3.4 } 2.2‹) and lateral decubitus positions (3.4 } 2.5‹, 5.0 } 3.5‹). Overall, 91%, 64.5%, and 56.3% were within 5‹ of the target angles in the navigation, supine goniometer, and lateral goniometer groups, respectively.
Conclusions The accuracy of cup alignment with the portable navigation system using the flip technique was significantly higher than that with the cup goniometer in the supine and lateral decubitus positions. en-copyright= kn-copyright= en-aut-name=TetsunagaTomonori en-aut-sei=Tetsunaga en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=YamadaKazuki en-aut-sei=Yamada en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KouraTakashi en-aut-sei=Koura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueTomohiro en-aut-sei=Inoue en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkudaRyuichiro en-aut-sei=Okuda en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MasadaYasutaka en-aut-sei=Masada en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MugurumaSho en-aut-sei=Muguruma en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkazakiYuki en-aut-sei=Okazaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthopaedics, Okayama Medical Center kn-affil= affil-num=9 en-affil=Department of Orthopaedics, Faculty 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=hip kn-keyword=hip en-keyword=navigation system kn-keyword=navigation system en-keyword=portable navigation kn-keyword=portable navigation en-keyword=retrospective study kn-keyword=retrospective study en-keyword=total hip arthroplasty (tha) kn-keyword=total hip arthroplasty (tha) 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=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 ƒ¢MMPE was observed in the TSS group compared to the TSS-PM group, whereas no significant difference was observed in ƒ¢MMEV.
Conclusion: TSS and TSS-PM repair techniques helped decrease MMEV at 90‹ of knee flexion, whereas a significantly decreased ƒ¢MMPE 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 ƒ¢MMPE 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=27 cd-vols= no-issue=7 article-no= start-page=e70673 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=Potential of quantitative X]ray imaging from photon]counting CT: A novel analysis based on effective atomic number and physical density en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Conventional CT assessment of lung lesions is based mainly on morphological features. CT values represent relative X-ray attenuation that does not directly reflect tissue composition and/or physical density. Quantitative imaging using photon-counting CT (PC-CT) has the potential to provide quantitative parameters, such as effective atomic number (Zeff) and effective physical density (ƒÏeff).
Purpose: The purpose is to develop and demonstrate the potential of an algorithm that generates both the Zeff and ƒÏeff images, derived directly from virtual monoenergetic images (VMIs) acquired with a clinical PC-CT system.
Methods: The ƒÏeff image was generated by fitting a database of mass attenuation coefficients (ƒÊ/ƒÏ) to the measured linear attenuation coefficients (ƒÊ), which were obtained from two VMIs at 70 and 100 keV. As an effective material, Zeff information was also determined and fed back into the ƒÏeff calculation. An in-house low-density phantom was scanned for quantitative evaluation of ƒÏeff. In addition, to demonstrate the applicability of our procedure to actual clinical imaging, representative chest PC-CT images from patients were analyzed.
Results: In experiments using low-density phantoms, the CT values did not necessarily correlate with Zeff values, but they showed a very good correlation with the ƒÏeff values. The ƒÏeff values calculated using our procedure correlated well with the correct values of ƒÏ. A relative root mean square error of ƒÏeff calculation was 5.5%. Furthermore, we found that in pulmonary diagnosis, image contrast information from ƒÏeff makes it easier to identify and distinguish lesions compared to that from Zeff.
Conclusions: The proposed procedure directly generated Zeff and ƒÏeff images from PC-CT data and enabled quantitative interpretation of CT value in terms of elemental composition and physical density. In this study, the feasibility of generating Zeff and ƒÏeff images was demonstrated. en-copyright= kn-copyright= en-aut-name=AsaharaTakashi en-aut-sei=Asahara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishigamiRina en-aut-sei=Nishigami en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimotoNatsumi en-aut-sei=Kimoto en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitaniMana en-aut-sei=Mitani en-aut-mei=Mana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 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=8 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=9 ORCID= en-aut-name=HayashiHiroaki en-aut-sei=Hayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=3 en-affil=Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University kn-affil= affil-num=4 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=5 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital 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, Faculty of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=College of Transdisciplinary Sciences for Innovation Kanazawa University Kanazawa Ishikawa Japan kn-affil= en-keyword=computed tomography kn-keyword=computed tomography en-keyword=density image kn-keyword=density image en-keyword=photon-counting kn-keyword=photon-counting en-keyword=virtual monoenergetic image kn-keyword=virtual monoenergetic image en-keyword=X-ray diagnosis kn-keyword=X-ray diagnosis END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=4 article-no= start-page=e70090 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260710 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Frontotemporal Lobar Degeneration]TDP Type C With Striatal Glial Cytoplasmic Inclusions and Motor Neuron Degeneration en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=UchinoAkiko en-aut-sei=Uchino en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanemaruKazutomi en-aut-sei=Kanemaru en-aut-mei=Kazutomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TarutaniAiri en-aut-sei=Tarutani en-aut-mei=Airi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HasegawaMasato en-aut-sei=Hasegawa en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaruseHiroya en-aut-sei=Naruse en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=MurayamaShigeo en-aut-sei=Murayama en-aut-mei=Shigeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SaitoYuko en-aut-sei=Saito en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology kn-affil= affil-num=2 en-affil=Department of Neurology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology kn-affil= affil-num=3 en-affil=Department of Clinical Medical Sciences, Tokyo Metropolitan Institute of Medical Science kn-affil= affil-num=4 en-affil=Department of Clinical Medical Sciences, Tokyo Metropolitan Institute of Medical Science kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology kn-affil= affil-num=8 en-affil=Department of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology kn-affil= en-keyword=amyotrophic lateral sclerosis kn-keyword=amyotrophic lateral sclerosis en-keyword=annexin A11 kn-keyword=annexin A11 en-keyword=corticobasal syndrome kn-keyword=corticobasal syndrome en-keyword=frontotemporal lobar degeneration kn-keyword=frontotemporal lobar degeneration en-keyword=glial cytoplasmic inclusions kn-keyword=glial cytoplasmic inclusions en-keyword=motor neuron disease kn-keyword=motor neuron disease en-keyword=TDP-43 kn-keyword=TDP-43 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 ƒÌƒ®/ƒÌOZ is approximately 2.5 for aqueous solutions, similar to that observed in polystyrene in a theta solvent. This similarity may arise because the crossover concentration between the semidilute and concentrated regions c?? is close to the overlap concentration c?. en-copyright= kn-copyright= en-aut-name=MengLingzi en-aut-sei=Meng en-aut-mei=Lingzi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwatoRene en-aut-sei=Iwato en-aut-mei=Rene kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeTakaichi en-aut-sei=Watanabe en-aut-mei=Takaichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LopezCarlos G. en-aut-sei=Lopez en-aut-mei=Carlos G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Materials Science and Engineering, The Pennsylvania State University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Materials Science and Engineering, The Pennsylvania State University kn-affil= en-keyword=Pullulan kn-keyword=Pullulan en-keyword=Osmotic pressure kn-keyword=Osmotic pressure en-keyword=Correlation length kn-keyword=Correlation length en-keyword=Semidilute solutions kn-keyword=Semidilute solutions en-keyword=Concentrated solutions kn-keyword=Concentrated solutions en-keyword=Viscosity kn-keyword=Viscosity en-keyword=SAXS kn-keyword=SAXS en-keyword=SANS kn-keyword=SANS en-keyword=DLS kn-keyword=DLS END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e02824-25 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260724 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Escalation of CTX-M-producing extensively drug-resistant Shigella spp. in Kolkata, India, following the COVID-19 pandemic en-subtitle= kn-subtitle= en-abstract= kn-abstract=Shigella spp. is recognized by the World Health Organization as a high-priority pathogen due to its global prevalence, unique pathogenic mechanisms, and growing antimicrobial resistance (AMR). Nearly half of all Shigella strains worldwide are now multidrug-resistant (MDR), and the emergence of extensively drug-resistant (XDR) variants?resistant to ciprofloxacin, ceftriaxone, and azithromycin?has severely limited effective treatment options. The present study is based on prospective laboratory surveillance involving 323 Shigella isolates collected during 2021?2023, with pre-COVID-19 pandemic data included from a previously published study solely for historical comparison. The presence of antibiotic resistance genes (ARGs) was investigated, and whole-genome sequencing (WGS) was performed on representative isolates to assess phylogenetic relatedness with global isolates. Approximately 10% of isolates exhibited resistance to third-generation cephalosporins. While only 3% of Shigella isolates carried the blaCTX-M-15 gene from 2013 to 2019, its prevalence increased to 26% by 2022?2023. Among 38 ceftriaxone-resistant S. sonnei isolates, 33 were also resistant to azithromycin, categorizing them as XDR. These isolates showed 48% clonal similarity and high phylogenetic resemblance to the isolates reported from England. Hybrid genome assembly revealed a plasmid harboring both the blaCTX-M-15 and mphA ARGs. Conjugation experiments and plasmid profiling confirmed the plasmidfs transferability. We report a rising trend in third-generation cephalosporin resistance among Shigella spp., primarily driven by the spread of extended-spectrum ƒÀ-lactamase-producing S. flexneri and the emergence of XDR S. sonnei. These findings underscore the urgent need for strengthened national AMR containment strategies and enhanced international surveillance of cephalosporin-resistant Shigella to mitigate this growing public health threat. en-copyright= kn-copyright= en-aut-name=BosePuja en-aut-sei=Bose en-aut-mei=Puja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HalderGourab en-aut-sei=Halder en-aut-mei=Gourab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KayetPratanu en-aut-sei=Kayet en-aut-mei=Pratanu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChowdhuryGoutam en-aut-sei=Chowdhury en-aut-mei=Goutam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BasakSurajit en-aut-sei=Basak en-aut-mei=Surajit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=RoyDeboleena en-aut-sei=Roy en-aut-mei=Deboleena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ImamuraDaisuke en-aut-sei=Imamura en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoritaMasatomo en-aut-sei=Morita en-aut-mei=Masatomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=RamamurthyThandavarayan en-aut-sei=Ramamurthy en-aut-mei=Thandavarayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KoleyHemanta en-aut-sei=Koley en-aut-mei=Hemanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DasSantasabuj en-aut-sei=Das en-aut-mei=Santasabuj kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MukhopadhyayAsish Kumar en-aut-sei=Mukhopadhyay en-aut-mei=Asish Kumar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=2 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=3 en-affil=Division of Bioinformatics, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=4 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=5 en-affil=Division of Bioinformatics, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=6 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=7 en-affil=Research Center for Intestinal Health Science, Okayama University kn-affil= affil-num=8 en-affil=Research Center for Intestinal Health Science, Okayama University kn-affil= affil-num=9 en-affil=Department of Bacteriology I, National Institute of Infectious Diseases kn-affil= affil-num=10 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=11 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=12 en-affil=Division of Clinical Medicine, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=13 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections kn-affil= en-keyword=dysentery kn-keyword=dysentery en-keyword=AMR kn-keyword=AMR en-keyword=XDR kn-keyword=XDR en-keyword=Shigella spp. kn-keyword=Shigella spp. en-keyword=CTX-M kn-keyword=CTX-M en-keyword=plasmid kn-keyword=plasmid en-keyword=transconjugants kn-keyword=transconjugants en-keyword=PFGE kn-keyword=PFGE en-keyword=WGS kn-keyword=WGS END start-ver=1.4 cd-journal=joma no-vol=49 cd-vols= no-issue=7 article-no= start-page=1992 end-page=2003 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260514 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of population-approach programs promoting salt reduction and potassium intake in Japan: the Population-based Sodium/Potassium Improvement Program (PoSPIP) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Reducing sodium intake in populations is essential, but insufficient for preventing and managing high blood pressure, while the importance of increasing potassium intake is overlooked. We investigated the effects of 1-year population-approach programs (2021?2022) promoting salt reduction and potassium intake using urinalysis feedback and food environment improvement. This retrospective observational study included 7649 participants (mean age, 54.0 years; 45.3% women) from 11 municipalities and 4 workplaces. Outcomes in intensive support programs?including urinary sodium, potassium, and sodium-to-potassium (Na/K) ratio measurements with feedback, dietary promotion, and food environment improvement?were compared with standard support programs providing usual health guidance. In linear regression adjusted for demographics, lifestyle factors, and medical history, the reduction in urinary Na/K ratio was greater in the intensive support group (n?=?4064) than in the standard support group (n?=?3585) (mean difference ?0.14 [95% confidence interval, ?0.27 to ?0.01]). Although estimated potassium intake decreased in both groups, the decline was smaller in the intensive support group (mean difference 31 [12 to 51] mg/day). Estimated salt intake did not differ between the groups. The intensive support group showed greater increases in diastolic blood pressure and high-density lipoprotein cholesterol and smaller increases in blood glucose, as well as greater reductions in hemoglobin A1c and Salt Check Sheet scores. Mean differences between the groups for endpoints were not heterogeneous across intensive support program types. Our findings support the development of hypertension prevention and management strategies that promote healthier dietary behaviors and can be implemented in community and workplace settings, with broad public health applicability. en-copyright= kn-copyright= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KinutaMinako en-aut-sei=Kinuta en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhkuboTakayoshi en-aut-sei=Ohkubo en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuchihashiTakuya en-aut-sei=Tsuchihashi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshitaKatsushi en-aut-sei=Yoshita en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakemiYukari en-aut-sei=Takemi en-aut-mei=Yukari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HayabuchiHitomi en-aut-sei=Hayabuchi en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamiYukiko en-aut-sei=Okami en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KitaokaKaori en-aut-sei=Kitaoka en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakaguchiKeiko en-aut-sei=Sakaguchi en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HozawaAtsushi en-aut-sei=Hozawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkamuraTomonori en-aut-sei=Okamura en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ItohHiroshi en-aut-sei=Itoh en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=RakugiHiromi en-aut-sei=Rakugi en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NodeKoichi en-aut-sei=Node en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MiuraKatsuyuki en-aut-sei=Miura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Hygiene and Public Health, Teikyo University School of Medicine kn-affil= affil-num=4 en-affil=Cardiovascular Center, Steel Memorial Yawata Hospital kn-affil= affil-num=5 en-affil=Department of Public Health, Nutrition, School of Human Life and Ecology, Osaka Metropolitan University kn-affil= affil-num=6 en-affil=Faculty of Nutrition, Kagawa Nutrition University kn-affil= affil-num=7 en-affil=Graduate School of Health and Environmental Sciences, Fukuoka Womenfs University kn-affil= affil-num=8 en-affil=Gunma University Center for Food Science and Wellness kn-affil= affil-num=9 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=10 en-affil=Faculty of Nursing and Nutrition, Shukutoku University kn-affil= affil-num=11 en-affil=Division of Epidemiology, School of Public Health, Tohoku University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Preventive Medicine and Public Health, Keio University School of Medicine kn-affil= affil-num=13 en-affil=Japanese Society of Hypertension kn-affil= affil-num=14 en-affil=Japanese Society of Hypertension kn-affil= affil-num=15 en-affil=Japanese Society of Hypertension kn-affil= affil-num=16 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= en-keyword=Implemental hypertension kn-keyword=Implemental hypertension en-keyword=Sodium kn-keyword=Sodium en-keyword=Potassium kn-keyword=Potassium en-keyword=Urinalysis kn-keyword=Urinalysis en-keyword=Food environment kn-keyword=Food environment END start-ver=1.4 cd-journal=joma no-vol=2026 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Carcinoma ex Pleomorphic Adenoma With an Epithelial]Myoepithelial Carcinoma Component in the Submandibular Gland: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Carcinoma ex pleomorphic adenoma (CXPA) is an uncommon malignant salivary gland tumor arising from pleomorphic adenoma, whereas epithelial-myoepithelial carcinoma (EMC) is a rare low-grade salivary gland malignancy. CXPA with an EMC component in the submandibular gland is uncommon.
Case Report: A 65-year-old man presented with a painless, firm mass in the left submandibular region and weakness of the left lower lip. Computed tomography and magnetic resonance imaging demonstrated an irregular submandibular mass, and FDG-PET/CT showed increased uptake (maximum standardized uptake value, 9.2). Core biopsy suggested pleomorphic adenoma; however, the clinical and radiological findings strongly indicated malignancy. Incisional biopsy was therefore performed under general anesthesia, with a plan to proceed to definitive treatment if malignancy was confirmed. Intraoperative histopathological examination revealed a malignant salivary gland tumor, and tumor resection with neck dissection was completed during the same procedure. Histopathological examination showed invasive CXPA with an EMC component, accompanied by extracapsular invasion exceeding 6?mm, perineural invasion, and extension into adjacent muscle (pT3N0). Although surgical margins were negative, pulmonary metastases developed 12 months after surgery, followed by suspected pleural dissemination and spinal canal extension. The patient declined further aggressive treatment and died of the disease 48 months after surgery.
Conclusion: This case highlights the importance of integrating clinical, radiological, and pathological findings for accurate diagnosis of salivary gland tumors, particularly when biopsy results are inconsistent with clinical suspicion. en-copyright= kn-copyright= en-aut-name=YasuharaTomohiro en-aut-sei=Yasuhara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MasuiMasanori en-aut-sei=Masui en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakakuraHiroaki en-aut-sei=Takakura en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwataEiji en-aut-sei=Iwata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KadoyaKoichi en-aut-sei=Kadoya en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UmemoriKoki en-aut-sei=Umemori en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshiokaNorie en-aut-sei=Yoshioka en-aut-mei=Norie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=carcinoma ex pleomorphic adenoma kn-keyword=carcinoma ex pleomorphic adenoma en-keyword=case report kn-keyword=case report en-keyword=epithelial-myoepithelial carcinoma kn-keyword=epithelial-myoepithelial carcinoma en-keyword=salivary gland neoplasm kn-keyword=salivary gland neoplasm en-keyword=submandibular gland kn-keyword=submandibular gland END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260722 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dissociation between globe shape-induced rectus muscle pulley displacement and abduction limitation in patients aged 40?years and older with high myopic strabismus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose We hypothesized that high myopia (HM)-induced globe deformation displaces rectus muscle (RM) pulleys, contributing to mild ocular motility restriction. This study investigated the effects of globe shape on RM pulley positions in older Japanese patients with acquired strabismus (AS) and mild motility restriction?defined as the ability to abduct both eyes beyond the midline.
Methods In this retrospective case series, 28 patients (mean age?}?standard deviation: 61.2?}?9.0 years) with adult-onset AS were included: 6 patients with (LAB group) and 22 patients without abduction limitation (NLAB group). In each subject, the eye with the longer axial length (AL???26 mm), measured using an AL measurement apparatus, was analyzed using magnetic resonance imaging (MRI). RM pulley positions relative to the globe center and equatorial diameter (ED) were measured; the ED-to-AL ratio (EAR) was calculated. We compared these parameters between groups and analyzed correlations of globe-shape factors (EAR, AL, and ED) with pulley positions and age.
Results No significant differences in EAR, AL, ED, or pulley positions were detected between LAB and NLAB groups, possibly owing to the limited sample size and group imbalance, in the analyzed eyes. However, as EAR decreased (prolate deformation), the superior rectus (SR) pulley (r?=?0.68, P? Conclusions In older Japanese patients with HM and AS, prolate globe deformation was associated with age and significantly correlated with SR and IR pulley positions. While the direct relationship between these structural changes and the clinical degree of mild abduction limitation requires further investigation in larger cohorts, EAR sensitively reflected age-related morphological shifts; thus, when used in conjunction with AL, EAR may represent a readily measurable MRI-based parameter associated with restrictive motility tendencies in strabismus with high myopia. en-copyright= kn-copyright= en-aut-name=KonoReika en-aut-sei=Kono en-aut-mei=Reika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamasakiIchiro en-aut-sei=Hamasaki en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KishimotoFumiko en-aut-sei=Kishimoto en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShibataKiyo en-aut-sei=Shibata en-aut-mei=Kiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MorisawaShin en-aut-sei=Morisawa en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Lino Eye Clinic kn-affil= affil-num=3 en-affil=Division of Ophthalmology, Ibara City Hospital kn-affil= affil-num=4 en-affil=Lino Eye Clinic kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Heavy eye syndrome kn-keyword=Heavy eye syndrome en-keyword=High myopia kn-keyword=High myopia en-keyword=Magnetic resonance imaging kn-keyword=Magnetic resonance imaging en-keyword=Prolate deformation kn-keyword=Prolate deformation en-keyword=Rectus muscle pulley kn-keyword=Rectus muscle pulley en-keyword=Strabismus kn-keyword=Strabismus END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=2 article-no= start-page=e70289 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260331 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recurrence of Pulmonary Hypertension After Unilateral Lung Transplantation: Histological Evidence of Vasoconstrictive Mechanism en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary hypertension (PH) is widely recognized as a disease driven by both vasoconstriction and vascular remodeling. Vasoconstriction is thought to play a predominant role in the early stages of PH, whereas the contribution of vascular remodeling increases as the disease progresses. However, clinical or histological evidence of this pathological progression has not been reported. We describe a case of recurrent PH after unilateral right lung transplantation, ultimately requiring bilateral transplantation 9 years later, and discuss the pathogenesis of PH based on histological findings in the transplanted normal lungs and changes in pulmonary blood flow observed by lung perfusion scintigraphy. Serial lung perfusion scintigraphy revealed a dynamic shift in pulmonary blood flow, initially favoring the transplanted lung, followed by a gradual decline. Histological examination demonstrated that the right lung of the second transplantation showed minimal vascular remodeling. These findings provide compelling evidence that vasoconstriction was the predominant contributor to PH after the first transplantation, offering unique insight into early PH pathobiology. 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=KondoMegumi en-aut-sei=Kondo en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IchimuraKoichi en-aut-sei=Ichimura en-aut-mei=Koichi 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=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, 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 Pathology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=4 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital 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=Center for Advanced Heart Failure, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=pulmonary arterial hypertension kn-keyword=pulmonary arterial hypertension en-keyword=vascular remodeling kn-keyword=vascular remodeling en-keyword=vasoconstriction kn-keyword=vasoconstriction 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? 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=33 cd-vols= no-issue=2 article-no= start-page=228 end-page=236 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Acquired LCAT Deficiency with the Discrepancy between Spontaneous Resolution of Proteinuria and Continually Low HDL Cholesterol Levels en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 79-year-old Chinese man was referred for nephrotic syndrome (proteinuria 4.4 g/day). In blood tests, serum high-density lipoprotein (HDL) cholesterol was undetectable, and the esterified cholesterol to total cholesterol ratio was very low. Lecithin: cholesterol acyltransferase (LCAT) activity was also undetectable. Since he had neither corneal opacity nor pathological mutations in the LCAT gene and anti-LCAT antibodies were detected in serum, a diagnosis of acquired LCAT deficiency was made. Renal biopsy revealed glomerulopathy associated with LCAT deficiency and membranous nephropathy (MN). Since the patientfs proteinuria did not improve despite prescribing an angiotensin II receptor blocker (ARB), we suggested the prescription of prednisolone, but he returned to China due to the expiration of his residence visa for Japan. One year after the initial visit, his proteinuria had improved to 0.9 g/day without immunosuppressive therapy. However, his HDL cholesterol level was still low at around 3 mg/dL, indicating a discrepancy between remission of nephrotic syndrome and lack of improvement in lipid levels.
Of the 11 patients with acquired LCAT deficiency reported to date, 4 with undetectable LCAT activity and MN on renal biopsy required immunosuppressive therapy to alleviate proteinuria. The present patient was prescribed only an ARB according to his preference, which happened to be consistent with the MN treatment guideline that states, gWait 6 months for spontaneous remission while using maximal antiproteinuric therapy.h The clinical course of acquired LCAT deficiency varies, and further case reports are needed to determine the necessity of immunosuppressive therapy. en-copyright= kn-copyright= en-aut-name=MatsuoMiki en-aut-sei=Matsuo en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OguraMasatsune en-aut-sei=Ogura en-aut-mei=Masatsune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurodaMasayuki en-aut-sei=Kuroda en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArisatoTetsuya en-aut-sei=Arisato en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KishidaMasatsugu en-aut-sei=Kishida en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Harada-ShibaMariko en-aut-sei=Harada-Shiba en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YokoteKoutaro en-aut-sei=Yokote en-aut-mei=Koutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshiharaFumiki en-aut-sei=Yoshihara en-aut-mei=Fumiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Nephrology and Hypertension, National Cerebral and Cardiovascular Center kn-affil= affil-num=2 en-affil=Department of Clinical Laboratory Technology, Faculty of Medical Science, Juntendo University kn-affil= affil-num=3 en-affil=Center for Advanced Medicine, Chiba University Hospital, Chiba University kn-affil= affil-num=4 en-affil=Department of Nephrology and Hypertension, National Cerebral and Cardiovascular Center kn-affil= affil-num=5 en-affil=Department of Nephrology and Hypertension, National Cerebral and Cardiovascular Center kn-affil= affil-num=6 en-affil=Cardiovascular Center, Osaka Medical and Pharmaceutical University kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Nephrology and Hypertension, National Cerebral and Cardiovascular Center kn-affil= en-keyword=Acquired LCAT deficiency kn-keyword=Acquired LCAT deficiency en-keyword=HDL deficiency kn-keyword=HDL deficiency en-keyword=Nephrotic syndrome kn-keyword=Nephrotic syndrome en-keyword=Membranous glomerulonephritis kn-keyword=Membranous glomerulonephritis END start-ver=1.4 cd-journal=joma no-vol=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 weeksf 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. Lukefs International University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Medical Development Field, Okayama University kn-affil= affil-num=4 en-affil=Department of Orthodontics, Dental Unit, TMSS Medical College & Rafatullah Community Hospital kn-affil= affil-num=5 en-affil=Department of Community and Global Health, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Office of International Academic Affairs, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=8 en-affil=Department of Periodontology and Oral Pathology, Holy Family Red Crescent Medical College Hospital kn-affil= affil-num=9 en-affil=Department of Periodontology, Dental Unit, TMSS Medical College & Rafatullah Community Hospital kn-affil= affil-num=10 en-affil=Department of Obstetrics & Gynecology, Holy Family Red Crescent Medical College Hospital kn-affil= affil-num=11 en-affil=Department of Obstetrics & Gynecology, TMSS Medical College & Rafatullah Community Hospital kn-affil= affil-num=12 en-affil=Department of Molecular and Cellular Biochemistry, Division of Oral Health, Brain Health and Total Health, Faculty of Dental Science, Kyushu University kn-affil= affil-num=13 en-affil=Global Communication Center, Grameen Communications kn-affil= affil-num=14 en-affil=Global Communication Center, Grameen Communications kn-affil= affil-num=15 en-affil=Department of Medical Informatics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=16 en-affil=Division of Healthcare Digital Transformation, Kyushu University kn-affil= affil-num=17 en-affil=Department of Research Promotion, Institute for Asian and Oceanian Studies, Kyushu University kn-affil= en-keyword=Preterm birth kn-keyword=Preterm birth en-keyword=Low birth weight kn-keyword=Low birth weight en-keyword=Oral health kn-keyword=Oral health en-keyword=Periodontal treatment kn-keyword=Periodontal treatment en-keyword=Chlorhexidine gluconate mouthwash kn-keyword=Chlorhexidine gluconate mouthwash en-keyword=Randomized controlled trial kn-keyword=Randomized controlled trial en-keyword=Bangladesh kn-keyword=Bangladesh END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=19 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Plasma expression levels of microRNA-101 are downregulated in patients with Parkinsonfs disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective Parkinsonfs 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=Parkinsonfs disease kn-keyword=Parkinsonfs 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=53 cd-vols= no-issue=14 article-no= start-page=e2026GL121981 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260710 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Calcium Solubility of Bridgmanite in Subducted Basalt in Earth's Lower Mantle en-subtitle= kn-subtitle= en-abstract= kn-abstract=The calcium solubility in bridgmanite and the resulting abundance of davemaoite under lower-mantle pressure-temperature conditions have been under debate following a recent report of extensive calcium dissolution in bridgmanite. We experimentally investigated the calcium solubility in bridgmanite in a basaltic composition at pressures up to 125 GPa and temperatures up to 3,520 K. Our experimental data are modeled thermodynamically along the bridgmanite-davemaoite solvus to quantify the calcium solubility in bridgmanite and the davemaoite proportion in basaltic and pyrolitic assemblages along lower mantle geotherms. Our results indicate that bridgmanite hosts only 0.001?0.03 Ca cations per formula unit in the lower mantle, while davemaoite remains as an abundant mineral, accounting for 8 and 25 vol% of pyrolitic and basaltic mineralogical models, respectively, along representative lower-mantle geotherms. Our thermoelastic modeling further indicates that the effect of calcium dissolution on the density and bulk sound velocity of lower-mantle assemblages is negligible. en-copyright= kn-copyright= en-aut-name=ZhangChengwei en-aut-sei=Zhang en-aut-mei=Chengwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshinoTakashi en-aut-sei=Yoshino en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=El GhazaouiElias en-aut-sei=El Ghazaoui en-aut-mei=Elias kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=CharitonStella en-aut-sei=Chariton en-aut-mei=Stella kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=PrakapenkaVitali B. en-aut-sei=Prakapenka en-aut-mei=Vitali B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LiLuo en-aut-sei=Li en-aut-mei=Luo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhangYanyao en-aut-sei=Zhang en-aut-mei=Yanyao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LinJung]Fu en-aut-sei=Lin en-aut-mei=Jung]Fu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Earth and Planetary Sciences, Jackson School of Geosciences The University of Texas at Austin kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=School of Earth and Environmental Sciences, Seoul National University kn-affil= affil-num=4 en-affil=Center for Advanced Radiation Sources, The University of Chicago kn-affil= affil-num=5 en-affil=Center for Advanced Radiation Sources, The University of Chicago kn-affil= affil-num=6 en-affil=Department of Earth and Planetary Sciences, Jackson School of Geosciences The University of Texas at Austin kn-affil= affil-num=7 en-affil=Earth and Planetary Sciences, Stanford University kn-affil= affil-num=8 en-affil=Department of Earth and Planetary Sciences, Jackson School of Geosciences The University of Texas at Austin kn-affil= END start-ver=1.4 cd-journal=joma no-vol=114 cd-vols= no-issue=3 article-no= start-page=486 end-page=489 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Heavy Paragonimiasis Involving a Multi-Organ Presentation with Hypereosinophilia and Hepatic Migration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Paragonimiasis is a parasitic disease caused by the genus Paragonimus, typically transmitted through the ingestion of raw or undercooked freshwater crabs. Although pulmonary involvement is typical, ectopic migration to subcutaneous or hepatic sites is rare and poses diagnostic challenges. A case of paragonimiasis in a 29-year-old Cambodian woman residing in Japan who presented with painless subcutaneous nodules on the chest and abdomen is reported in the current study. She had consumed raw crab 4 months before presentation. Laboratory findings revealed marked eosinophilia (21,000/?L) and elevated immunoglobulin E (5,049 IU/mL). Computed tomography scans revealed pleural effusion, club-shaped pulmonary consolidation, funicular hypodense lesions in the liver, and subcutaneous lesions. Stool and sputum test results were negative for parasite eggs; however, a microplate ELISA indicated a Paragonimus westermani infection. The patient responded well to 3 consecutive days of praziquantel (75 mg/kg/day) and was discharged a week later. This case highlights the importance of considering paragonimiasis in patients with unexplained subcutaneous nodules and eosinophilia, especially when supported by dietary risk factors. en-copyright= kn-copyright= en-aut-name=AkazawaHidemasa en-aut-sei=Akazawa en-aut-mei=Hidemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamotoKenta en-aut-sei=Nakamoto en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ManabeYohei en-aut-sei=Manabe en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Kokubo-TanakaMio en-aut-sei=Kokubo-Tanaka en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaruyamaHaruhiko en-aut-sei=Maruyama en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Parasitology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki kn-affil= affil-num=8 en-affil=Division of Parasitology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki kn-affil= affil-num=9 en-affil=Department of General Medicine, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=3482 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Atomic imaging for hydrogen and boron aggregates in boron-doped diamond by spectro-photoelectron holography en-subtitle= kn-subtitle= en-abstract= kn-abstract=The electrical properties of diamond are modulated by impurity doping. Isolated substitutional boron atoms introduce holes; however, the fraction of electrically inactive boron atoms increases at higher doping concentrations. This has been attributed to boron aggregation and hydrogen passivation, although their structural identification based on atomic arrangement has yet to be experimentally verified. Here we show the origin of multiple chemical states in homoepitaxially grown boron-doped diamond thin films by analyzing the atomic environment of boron using spectro-photoelectron holography. Our analysis identifies boron dimers and boron-hydrogen complexes, with hydrogen occupying different atomic sites that give rise to distinct chemical shifts. These results suggest that hydrogen incorporation during growth leads to passivation of boron acceptors. We demonstrate that photoelectron holography serves as a promising tool for imaging hydrogen as well as determining the atomic sites of dopants. en-copyright= kn-copyright= en-aut-name=TomitaHiroto en-aut-sei=Tomita en-aut-mei=Hiroto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HosodaWataru en-aut-sei=Hosoda en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaniguchiTakumi en-aut-sei=Taniguchi en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiwaraHirokazu en-aut-sei=Fujiwara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KataokaNoriyuki en-aut-sei=Kataoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KageuraTaisuke en-aut-sei=Kageura en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakanoYoshihiko en-aut-sei=Takano en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaradaHiroshi en-aut-sei=Kawarada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OguchiTamio en-aut-sei=Oguchi en-aut-mei=Tamio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YokoyaTakayoshi en-aut-sei=Yokoya en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsushitaTomohiro en-aut-sei=Matsushita en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Graduate School of Science and Technology, Nara Institute of Science and Technology kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=5 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=6 en-affil=Sensing Technology Research Institute, National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=7 en-affil=Research Center for Materials Nanoarchitectonics, National Institute for Materials Science kn-affil= affil-num=8 en-affil=Faculty of Science and Engineering, Waseda University kn-affil= affil-num=9 en-affil=Center for Spintronics Research Network, The University of Osaka kn-affil= affil-num=10 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Science and Technology, Nara Institute of Science and Technology kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=16760 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260409 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Asthma-like bronchodilator responsiveness in patients with neuronal intranuclear inclusion disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative condition characterized by the presence of intranuclear inclusions in neuronal and visceral cells. Patients with NIID can present respiratory symptoms; however, data on pulmonary functions in NIID are lacking. This study investigated the respiratory conditions in NIID patients diagnosed with histopathological and genetic studies. We conducted two spirometries before and after administrating the bronchodilator in NIID patients with asthmatic histories or symptoms. We statistically compared pre- and post-measured values including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF). Before two spirometries, we also measured fractional concentration of exhaled nitric oxide (FeNO), if possible. Of the 51finally enrolled patients, 17 (33.3%, 95% CI 20.8% to 47.9%) patients had asthmatic histories or symptoms, and 14 patients received two spirometries. After administrating the bronchodilator, FEV1 and PEF significantly increased by 150 mL (6.01%, p?=?0.002) and 260 mL/s (6.72%, p?=?0.017), respectively. The median (interquartile range) of FeNO measured in nine patients was 15 (10?21) ppb. Patients with NIID have airflow reversibility like asthma. This condition appears to be less associated with airway inflammation and may be related to autonomic dysfunction. en-copyright= kn-copyright= en-aut-name=TaharaDaisuke en-aut-sei=Tahara en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TaharaNao en-aut-sei=Tahara en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TamaiChisato en-aut-sei=Tamai en-aut-mei=Chisato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkagiAkio en-aut-sei=Akagi en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RikuYuichi en-aut-sei=Riku en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyaharaHiroaki en-aut-sei=Miyahara en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobayashiRei en-aut-sei=Kobayashi en-aut-mei=Rei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkadaHisashi en-aut-sei=Okada en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawamotoMichi en-aut-sei=Kawamoto en-aut-mei=Michi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiiJunko en-aut-sei=Ishii en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamazakiHiroki en-aut-sei=Yamazaki en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KurashigeTakashi en-aut-sei=Kurashige en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SugiyamaAtsuhiko en-aut-sei=Sugiyama en-aut-mei=Atsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NagaishiAkiko en-aut-sei=Nagaishi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NishidaKatsuya en-aut-sei=Nishida en-aut-mei=Katsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SugieKazuma en-aut-sei=Sugie en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FukudomeTakayasu en-aut-sei=Fukudome en-aut-mei=Takayasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HasegawaKazuko en-aut-sei=Hasegawa en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KoikeHaruki en-aut-sei=Koike en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KasaiTakashi en-aut-sei=Kasai en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MizunoToshiki en-aut-sei=Mizuno en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=AndoMasahiro en-aut-sei=Ando en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HiguchiYujiro en-aut-sei=Higuchi en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=TanakaFumiaki en-aut-sei=Tanaka en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IzumiYuishin en-aut-sei=Izumi en-aut-mei=Yuishin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=SobueGen en-aut-sei=Sobue en-aut-mei=Gen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=IwasakiYasushi en-aut-sei=Iwasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=ItoSatoru en-aut-sei=Ito en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SoneJun en-aut-sei=Sone en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=2 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=3 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=4 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=5 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=6 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=7 en-affil=Department of Neurology, NHO Nagoya Medical Center kn-affil= affil-num=8 en-affil=Department of Neurology, NHO Nagoya Medical Center kn-affil= affil-num=9 en-affil=Department of Neurology, Kobe City Medical Center General Hospital kn-affil= affil-num=10 en-affil=Department of Neurology, Kobe City Medical Center General Hospital kn-affil= affil-num=11 en-affil=Department of Neurology, Tokushima University Graduate School of Biomedical Science kn-affil= affil-num=12 en-affil=Department of Neurology, NHO Kure Medical Center and Chugoku Cancer Center kn-affil= affil-num=13 en-affil=Department of Neurology, Chiba University kn-affil= affil-num=14 en-affil=Department of Neurology, NHO Nagasaki Kawatana Medical Center kn-affil= affil-num=15 en-affil=Department of Neurology, NHO Hyogo Chuo National Hospital kn-affil= affil-num=16 en-affil=Department of Neurology, Nara Medical University Hospital kn-affil= affil-num=17 en-affil=Department of Neurology, NHO Nagasaki Kawatana Medical Center kn-affil= affil-num=18 en-affil=Department of Neurology, NHO Sagamihara National Hospital kn-affil= affil-num=19 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=20 en-affil=Department of Neurology, Saga University kn-affil= affil-num=21 en-affil=Department of Neurology, Kyoto Prefectural University of Medicine kn-affil= affil-num=22 en-affil=Department of Neurology, Kyoto Prefectural University of Medicine kn-affil= affil-num=23 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=24 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=25 en-affil=Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine kn-affil= affil-num=26 en-affil=Department of Neurology, Tokushima University Graduate School of Biomedical Science kn-affil= affil-num=27 en-affil=Aichi Medical University kn-affil= affil-num=28 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=29 en-affil=Division of Respiratory Medicine and Allergology, Department of Internal Medicine, School of Medicine, Aichi Medical University kn-affil= affil-num=30 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= en-keyword=Asthma kn-keyword=Asthma en-keyword=Autonomic dysfunction kn-keyword=Autonomic dysfunction en-keyword=Cough kn-keyword=Cough en-keyword=Neuronal intranuclear inclusion disease kn-keyword=Neuronal intranuclear inclusion disease en-keyword=NOTCH2NLC kn-keyword=NOTCH2NLC en-keyword=Pulmonary function kn-keyword=Pulmonary function END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=838 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260418 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=In vivo activities of E1 elements in the insulin promoter en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this study, we evaluated the in vivo activity of the E1 element within the insulin promoter region. While we successfully obtained mice carrying a deletion exclusively in the E1 element of Ins2 (2E mice), we were unable to obtain mice with a deletion limited to the E1 element of Ins1. To assess the role of the E1 element in Ins1, we compared the mice carrying deletions in the GG2-GG1/A2-C1 elements with or without an additional E1 element deletion (1GC/1GCE mice). 1GCE2E mice developed diabetes. In contrast, 1GCE23 mice (without deletion in the E1 element of Ins2) did not develop diabetes, suggesting that the E1 element of Ins2 is critical for transcriptional regulation. Furthermore, 1GC2E mice (presence of the E1 element of Ins1) developed diabetes. However, the severity of the disease was milder in 1GC2E mice than in 1GCE2E mice, indicating that the E1 element of Ins1 also contributes to transcriptional regulation. These data suggest that the E1 elements in both Ins1/2 promoters are regulated for the in vivo transcription of insulin genes in mice. en-copyright= kn-copyright= en-aut-name=NoguchiHirofumi en-aut-sei=Noguchi en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Miyagi-ShiohiraChika en-aut-sei=Miyagi-Shiohira en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitohIssei en-aut-sei=Saitoh en-aut-mei=Issei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus kn-affil= affil-num=2 en-affil=Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatric Dentistry, Asahi University School of Dentistry kn-affil= END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=1050 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260423 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Differences in understanding of explanations and risk perception between dental staff and patients: a questionnaire study at a university hospital en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and purpose: Proper self-care necessitates behavioral changes, underpinned by correct knowledge. Oral health literacy (OHL) research constitutes a fundamental foundation for fostering effective self-care practices. However, the extent of the awareness gap between patients and dental staff regarding explanations provided during treatment remains unknown. This descriptive study was conducted to serve as an initial step in bridging this gap.
Methods: Questionnaires were distributed to 92 dental staff members and 205 patients at university hospitals, with responses from 72 staff members and 157 patients.
Results: In the category assessing understanding of explanations (patient vs. dental staff), patientsf self-assessed understanding exceeded the dental stafffs estimates in three aspects: disease name (p?=?0.03, r?=?0.17), treatment period (p?=?0.01, r?=?0.21), and pain relief (p?=?0.01, r?=?0.19). Regarding health self-awareness, the high-scoring group significantly outperformed the low-scoring group in explaining treatment risks (p?=?0.03, r?=?0.21) and understanding (p?=?0.01, r?=?0.23). Nevertheless, patientsf risk recognition was higher than that of dental staff in three aspects: root canal treatment (p? Conclusion: Dental staff should not be satisfied merely with having "explained" something to the patient; they must engage in a confirmation process to verify the patient's correct understanding of the information or to identify excessive anxiety. en-copyright= kn-copyright= en-aut-name=OtomoShiho en-aut-sei=Otomo en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujisakiMaoko en-aut-sei=Fujisaki en-aut-mei=Maoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanagaseRisako en-aut-sei=Yanagase en-aut-mei=Risako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NoritakeKanako en-aut-sei=Noritake en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanagiYoshinobu en-aut-sei=Yanagi en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugiharaTaro en-aut-sei=Sugihara en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=School of Environment and Society, Institute of Science Tokyo kn-affil= affil-num=2 en-affil=School of Environment and Society, Institute of Science Tokyo kn-affil= affil-num=3 en-affil=School of Environment and Society, Institute of Science Tokyo kn-affil= affil-num=4 en-affil=Institute of Science Tokyo Hospital, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=School of Environment and Society, Institute of Science Tokyo kn-affil= en-keyword=Dental care kn-keyword=Dental care en-keyword=Dentist-patient relations kn-keyword=Dentist-patient relations en-keyword=Recognition gaps kn-keyword=Recognition gaps en-keyword=Oral health literacy kn-keyword=Oral health literacy END start-ver=1.4 cd-journal=joma no-vol=2026 cd-vols= no-issue=1 article-no= start-page=2879891 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Rare Case of Hyperplastic Dental Follicle Presenting With an Unusually Large Radiolucent Area en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hyperplastic dental follicle (HDF) is a rare odontogenic hamartomatous lesion typically associated with unerupted teeth in children and adolescents and is often found incidentally on radiographic imaging. HDF usually presents as a pericoronal radiolucency of 2?3?mm in diameter and is commonly difficult to distinguish from dentigerous cysts on radiographs. We report an unusual case of HDF in an 11-year-old male who was referred for evaluation of delayed eruption of the left maxillary canine. Panoramic radiography and cone-beam computed tomography (CBCT) revealed a remarkably large radiolucent area, with a maximum dimension of 25.3?mm. The initial clinical diagnosis was a dentigerous cyst; however, incisional biopsy revealed solid tissue characteristics, and histopathological examination confirmed HDF, with no evidence of cystic lining, neoplastic transformation, or inflammation. Following the patientŒs and parentsŒ preference for complete removal, resection of the lesion together with extraction of the impacted canine was performed under general anesthesia. At the 6-month follow-up, no recurrence was observed and bone regeneration was confirmed on radiographic examination. This case underscores the diagnostic challenge posed by atypical radiographic findings and highlights the necessity of histopathological confirmation. Given the exceptional size and potential for recurrence, long-term follow-up is warranted. en-copyright= kn-copyright= en-aut-name=OtsukiSatoshi en-aut-sei=Otsuki en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KadoyaKoichi en-aut-sei=Kadoya en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiChizuru en-aut-sei=Kobayashi en-aut-mei=Chizuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawazuToshiyuki en-aut-sei=Kawazu en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=case report kn-keyword=case report en-keyword=hyperplastic dental follicle kn-keyword=hyperplastic dental follicle en-keyword=large radiolucent lesion kn-keyword=large radiolucent lesion en-keyword=odontogenic hamartoma kn-keyword=odontogenic hamartoma en-keyword=unerupted tooth kn-keyword=unerupted tooth END start-ver=1.4 cd-journal=joma no-vol=105 cd-vols= no-issue=7 article-no= start-page=105 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=WT1 mRNA in peripheral blood enables early prognostic stratification in AML patients receiving venetoclax and azacitidine therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Venetoclax and azacitidine (VEN/AZA), which target BCL-2 and DNA methylation, have demonstrated substantial efficacy, particularly in older or unfit patients with acute myeloid leukemia (AML). Wilmsf Tumor-1 (WT1) mRNA, measurable in peripheral blood (PB), is an established biomarker for monitoring treatment response and predicting AML prognosis. We conducted a retrospective analysis of patients with AML treated with VEN/AZA within the Okayama Hematology Study Group (OHSG). Patients who showed a marked reduction in PB WT1 mRNA levels from baseline after the first or second treatment cycle had significantly improved overall survival (OS) and progression-free survival (PFS). Moreover, achieving PB WT1 mRNA negativity-regardless of whether this occurred early or later in the therapy?was consistently associated with superior OS and PFS. These findings suggest that PB WT1 mRNA is a sensitive and reliable biomarker for predicting treatment response and long-term outcomes in patients with AML receiving VEN/AZA. en-copyright= kn-copyright= en-aut-name=SugiuraHiroyuki en-aut-sei=Sugiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=AsanoTakeru en-aut-sei=Asano en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiramatsuYasushi en-aut-sei=Hiramatsu en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UrataTomohiro en-aut-sei=Urata en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ImaiToshi en-aut-sei=Imai en-aut-mei=Toshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraMakoto en-aut-sei=Nakamura en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoKazuhiko en-aut-sei=Yamamoto en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshikawaTatsunori en-aut-sei=Ishikawa en-aut-mei=Tatsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MakitaMasanori en-aut-sei=Makita en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshiokaTakanori en-aut-sei=Yoshioka en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SunamiKazutaka en-aut-sei=Sunami en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SaekiKyosuke en-aut-sei=Saeki en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NawaYuichiro en-aut-sei=Nawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KimuraMaiko en-aut-sei=Kimura en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakeuchiMakoto en-aut-sei=Takeuchi en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AbeMasaya en-aut-sei=Abe en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=AsakuraShoji en-aut-sei=Asakura en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YanoTomofumi en-aut-sei=Yano en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Division of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=2 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= affil-num=7 en-affil=Department of Hematology, Okayama City Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Okayama City Hospital kn-affil= affil-num=9 en-affil=Department of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School Teachers kn-affil= affil-num=10 en-affil=Department of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School Teachers kn-affil= affil-num=11 en-affil=Department of Hematology, NHO Okayama Medical Center kn-affil= affil-num=12 en-affil=Department of Hematology, NHO Okayama Medical Center kn-affil= affil-num=13 en-affil=Division of Hematology, Ehime Prefectural Central Hospital kn-affil= affil-num=14 en-affil=Division of Hematology, Ehime Prefectural Central Hospital kn-affil= affil-num=15 en-affil=Department of Hematology, Japanese Red Cross Okayama Hospital kn-affil= affil-num=16 en-affil=Department of Hematology, Japanese Red Cross Okayama Hospital kn-affil= affil-num=17 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Internal Medicine, Okayama Rosai Hospital kn-affil= affil-num=19 en-affil=Department of Internal Medicine, Okayama Rosai Hospital kn-affil= affil-num=20 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=WT1 mRNA kn-keyword=WT1 mRNA en-keyword=Acute myeloid leukemia kn-keyword=Acute myeloid leukemia en-keyword=Venetoclax kn-keyword=Venetoclax en-keyword=Azacitidine kn-keyword=Azacitidine en-keyword=Measurable residual disease kn-keyword=Measurable residual disease END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=628 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=Sebastidae-specific food allergy causing anaphylaxis: a pediatric case report and fish allergen analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Fish allergy affects approximately 0?0.3% of the population. Parvalbumin is the major allergen in fish allergy, and patients with fish allergy sensitized to parvalbumin demonstrate allergic reactions to various fish species. However, a subset of patients exhibits allergic responses to only specific fish species. Fish of the Sebastidae family, widely consumed in Asian, North American, and European countries, has rarely been reported as an allergenic trigger.
Case presentation A 14-year-old Japanese boy visited our clinic for evaluation of fish allergy after experiencing allergic reactions to Sebastes alutus (Alaskan rockfish). He developed respiratory symptoms, eyelid edema, and skin erythema after consuming a meal containing Sebastes alutus, suggesting anaphylaxis; however, he was able to consume many other fish species without any issues. Skin prick tests and basophil activation tests using fish species from the Sebastidae family showed positive reactions, whereas other fish species that the patient could tolerate showed negative reactions. Immunoblot analysis performed to identify the causative allergen revealed two IgE-binding bands (17 and 110 kDa) in Sebastidae, distinct from parvalbumin. Mass spectrometry identified these proteins as alpha-actinin-3b, ATPase sarcoplasmic/endoplasmic reticulum Ca2?+?transporting 1, and several myosin-related proteins.
Conclusions This case highlights the need for clinicians to recognize fish allergy specific to the Sebastidae family. Identifying the causative non-parvalbumin allergens would improve understanding of fish allergy diversity and individualized dietary management for patients. Additional cases and detailed analyses are necessary to identify the specific allergens involved in Sebastidae allergy. en-copyright= kn-copyright= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UdaKazuhiro en-aut-sei=Uda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkedaMasanori en-aut-sei=Ikeda en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= affil-num=1 en-affil=Department of Pediatric Acute Diseases, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Food allergy kn-keyword=Food allergy en-keyword=Fish allergy kn-keyword=Fish allergy en-keyword=Sebastidae kn-keyword=Sebastidae en-keyword=Basophil activation test kn-keyword=Basophil activation test END start-ver=1.4 cd-journal=joma no-vol=34 cd-vols= no-issue=1 article-no= start-page=1 end-page=10 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=Similar functional outcomes but different remodeling patterns: A minimum 5-years radiographic comparison of short fit-and-fill stem and quadrangular taper stem en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: ACTIS and CORAIL are cementless titanium femoral stems with hydroxyapatite (HA) coating but differing macro-geometries: ACTIS features a variable triple-taper with a medial collar, whereas CORAIL is a straight double-tapered design available with or without a collar. We compared mid-term clinical and radiographic outcomes of these stems with a minimum 5-years follow-up.
Methods: We retrospectively reviewed 114 primary total hip arthroplasties using ACTIS (63 hips) or CORAIL (51 hips). Clinical outcomes and standardized radiographic parameters were assessed and compared between groups.
Results: The canal-fill ratio (CFR) was significantly greater at the proximal, middle, and distal levels in the ACTIS group. Spot-weld formation was more frequent with ACTIS than with CORAIL (58.7% vs 35.3%). In logistic regression, proximal CFR significantly predicted spot-weld formation for ACTIS, with an optimal cutoff of 66.2% (sensitivity 91.9%, specificity 72.0%). Rates of subsidence, radiolucent lines, and pedestal formation did not differ significantly between groups. No severe stress shielding was observed with ACTIS, whereas three CORAIL hips demonstrated severe stress shielding (0% vs 5.9%). Clinical scores improved significantly in both groups, with no significant between-group differences at final follow-up.
Conclusions: Both stems yielded favorable radiographic and clinical mid-term outcomes. In ACTIS, greater proximal canal fill was associated with radiographic osseointegration, suggesting proximal CFR as a probabilistic radiographic marker of stem ingrowth. en-copyright= kn-copyright= en-aut-name=MasadaYasutaka en-aut-sei=Masada en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TetsunagaTomonori en-aut-sei=Tetsunaga en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiwaraKazuo en-aut-sei=Fujiwara en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamadaKazuki en-aut-sei=Yamada en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueTomohiro en-aut-sei=Inoue en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkudaRyuichiro en-aut-sei=Okuda en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=OkazakiYuki en-aut-sei=Okazaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama City General Medical Center, Okayama City Hospital kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Center for Education in Medicine and Health 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= en-keyword=total hip arthroplasty kn-keyword=total hip arthroplasty en-keyword=ACTIS kn-keyword=ACTIS en-keyword=CORAIL kn-keyword=CORAIL en-keyword=mid-term outcome kn-keyword=mid-term outcome en-keyword=retrospective study kn-keyword=retrospective study END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=5862 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=The role of Pth1r in posterior cranium cartilage regulation and craniosynostosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Craniosynostosis is a major craniofacial congenital disorder that causes developmental complications. During normal cranial development, intramembranous ossification forms the flat bones and sutures, while cartilage appears transiently in the posterior calvarial region. However, in craniosynostosis, premature suture fusion disturbs normal calvarial morphogenesis. To clarify the role of transient cartilage in this morphogenetic disruption, we investigated its molecular regulation and pathology in mice, focusing on parathyroid hormone 1 receptor (Pth1r) signaling. Conditional deletion of Pth1r in the cranial mesenchyme unexpectedly caused acrocephalic dysmorphology and craniosynostosis, with altered cartilage differentiation. Occipito?interparietal synostosis consistently occurred in Pth1r-ablated Gli1+ and Acan+ lineages, but not after adult Gli1-CreERT2 deletion, indicating a developmental role. Bulk and single-cell RNA-seq analysis revealed nine mesenchymal subsets, with mutant cells showing abnormal chondrocyte differentiation and upregulated Indian hedgehog (Ihh) signaling. These findings indicate that Pth1r maintains proper chondrogenic regulation during calvarial development, and its loss induces craniosynostosis through Ihh overactivation. en-copyright= kn-copyright= en-aut-name=AmanoKatsuhiko en-aut-sei=Amano en-aut-mei=Katsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkuzakiDaisuke en-aut-sei=Okuzaki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujimotoYuji en-aut-sei=Fujimoto en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiuYu-Chen en-aut-sei=Liu en-aut-mei=Yu-Chen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KogoMikihiko en-aut-sei=Kogo en-aut-mei=Mikihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IidaSeiji en-aut-sei=Iida en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Laboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, University of Osaka kn-affil= affil-num=3 en-affil=Laboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, University of Osaka kn-affil= affil-num=4 en-affil=Laboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, University of Osaka kn-affil= affil-num=5 en-affil=The First Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=131 cd-vols= no-issue=7 article-no= start-page=e2025JE009578 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=Surface Geology and Evolution of Asteroid Ryugu: Insights From Hayabusa2 Global Mapping en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rubble-pile asteroids, characterized by loose aggregates of debris held together by gravity, represent both a significant planetary hazard and a key to understanding planetesimal formation. Geologic mapping of these bodies provides essential insights into their origins, evolution, and surface processes. This knowledge is crucial for advancing space mission capabilities, from precise navigation and safe sampling to assessing the feasibility of future asteroid mining. Here, we present the most comprehensive geologic map of Ryugu in comparison to previous early-stage and single-feature maps, integrating Optical Navigation Camera (ONC) mosaics, LIDAR-derived topography, Mobile Asteroid Surface Scout (MASCOT) descent images, and spectral slope data. The analysis includes reclassification of previously identified features and newly identified features from global to local scales. The geologic mapping technique followed United States Geological Survey (USGS) planetary cartography standards using the ArcGIS Pro platform. This global framework provides an essential geologic context for interpreting returned samples and constraining rubble-pile evolution. We identified geomorphological, structural, and surface texture units on Ryugu's unconsolidated rubble-pile surface using 0.2?0.7 m/pixel image mosaics. Elongated troughs at the poles and mirrored, oblique lineaments near the equatorial ridge are consistent with rotational strain. Compared with another rubble-pile asteroid Bennu, Ryugu shows a more uniform boulder distribution, and its immensely prominent equatorial ridge indicates a more intense period of rotational deformation. However, the western bulge deviates from this trend; its fewer boulders, underdeveloped ridges, and older degraded craters suggest selective resurfacing. These features show evidence of catastrophic disruption, rotational reshaping, and ongoing surface movement. en-copyright= kn-copyright= en-aut-name=VincentLisa M. en-aut-sei=Vincent en-aut-mei=Lisa M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RujTrishit en-aut-sei=Ruj en-aut-mei=Trishit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KomatsuGoro en-aut-sei=Komatsu en-aut-mei=Goro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=RayAditya en-aut-sei=Ray en-aut-mei=Aditya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuchiHiroshi en-aut-sei=Kikuchi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HemmiRyodo en-aut-sei=Hemmi en-aut-mei=Ryodo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyamotoHideaki en-aut-sei=Miyamoto en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugitaSeiji en-aut-sei=Sugita en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=the Hayabusa2 ONC science team en-aut-sei=the Hayabusa2 ONC science team en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Earth Sciences, Utrecht University kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=International Research School of Planetary Sciences, Universit? G. d'Annunzio kn-affil= affil-num=4 en-affil=Department of Geology, Presidency University kn-affil= affil-num=5 en-affil=Gakushuin University kn-affil= affil-num=6 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=7 en-affil=Department of Systems Innovation School of Engineering, The University of Tokyo kn-affil= affil-num=8 en-affil=Planetary Exploration Research Center, Chiba Institute of Technology kn-affil= affil-num=9 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=1 article-no= start-page=19 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=Performance of the modified 2022 ACR/EULAR giant cell arteritis classification criteria without age restriction for discriminating from Takayasu arteritis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective To evaluate the ability to discriminate giant cell arteritis (GCA) from Takayasu arteritis (TAK) according to the modified 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) GCA classification criteria.
Methods Patients enrolled in the Japanese nationwide retrospective registry were evaluated using the criteria with partial modification; wall thickening of descending thoracic-abdominal aorta were mainly diagnosed by contrast-enhanced computed tomography (CT) or magnetic resonance imaging instead of evaluating with positron emission tomography (PET)-CT. The discriminability of the criteria was evaluated using C-statistic (>?0.7: good ability).
Results Newly diagnosed patients with GCA (n?=?139) and TAK (n?=?129) were assessed, and 23.3% of TAK were aged 50 years or older at onset. The sensitivity of the modified 2022 ACR/EULAR GCA classification criteria with a score???6 was 82.0%, 68.5%, and 32.1% in all GCA, GCA with large-vessel involvement, and GCA without cranial arteritis, respectively. The specificity of the modified criteria was 96.1% for the 129 TAK as controls. Five patients with late-onset TAK met the modified criteria, and four had cranial signs and symptoms, two had bilateral axillary artery involvement, and four had descending thoracic-abdominal aorta involvement. The discriminability of the criteria was good (C-statistic: 0.986, 95% confidence interval [CI]: 0.976?0.996) and remained good after excluding age (C-statistic: 0.927, 95% CI: 0.894?0.961). The discriminability of a set of large-vessel lesions (bilateral axillary artery and descending thoracic-abdominal aorta) and inflammatory markers was markedly decreased with poor C-statistic value (C-statistic: 0.598, 95% CI: 0.530?0.667). Discriminability was improved after adding polymyalgia rheumatica (PMR) (C-statistic: 0.757, 95% CI: 0.700?0.813) or age (C-statistic: 0.913, 95%CI: 0.874?0.951) to the set of large-vessel lesions. In GCA patients with a score???5, 52% had bilateral subclavian and/or axillary artery involvement.
Conclusion The modified 2022 ACR/EULAR GCA classification criteria well performed in classifying GCA and TAK without PET-CT in routine clinical practice. A set of items included in the modified GCA classification criteria had good discriminative ability for GCA and TAK, even when age was excluded. However, age restriction or PMR was required to distinguish GCA without cranial lesions from TAK. en-copyright= kn-copyright= en-aut-name=SugiharaTakahiko en-aut-sei=Sugihara en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HarigaiMasayoshi en-aut-sei=Harigai en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=MaejimaYasuhiro en-aut-sei=Maejima en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshizakiJun en-aut-sei=Ishizaki en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeYoshiko en-aut-sei=Watanabe en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=DobashiHiroaki en-aut-sei=Dobashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KomagataYoshinori en-aut-sei=Komagata en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TamuraNaoto en-aut-sei=Tamura en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakaokaYoshikazu en-aut-sei=Nakaoka en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS) en-aut-sei=Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS) en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Rheumatology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= affil-num=2 en-affil=Division of Rheumatology, Department of Internal Medicine, Tokyo Womenfs Medical University School of Medicine kn-affil= affil-num=3 en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= affil-num=6 en-affil=Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of General Medicine, Kawasaki Medical School kn-affil= affil-num=8 en-affil=Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Department of Nephrology and Rheumatology, Kyorin University School of Medicine kn-affil= affil-num=10 en-affil=Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine kn-affil= affil-num=11 en-affil=Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute kn-affil= affil-num=12 en-affil= kn-affil= en-keyword=GCA kn-keyword=GCA en-keyword=TAK kn-keyword=TAK en-keyword=Classification criteria kn-keyword=Classification criteria en-keyword=Bilateral axillary artery kn-keyword=Bilateral axillary artery en-keyword=Descending thoracic-abdominal aorta kn-keyword=Descending thoracic-abdominal aorta en-keyword=Bilateral subclavian artery kn-keyword=Bilateral subclavian artery 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=136 cd-vols= no-issue=10 article-no= start-page=e195021 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Spatial single-cell proteotyping reveals immunotherapy-resistant features within the complex tumor microenvironment of metastatic NSCLC en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND. Immune checkpoint inhibitors (ICIs) targeting the programmed cell death 1 axis have revolutionized metastatic non?small cell lung cancer (mNSCLC) treatment. However, disease progression remains a concern, and the role of the complex tumor microenvironment (TME) in treatment failure is not fully understood.
METHODS. In this biomarker study involving 103 patients with mNSCLC, including 81 patients who received ICI treatment, we evaluated the association between heterogeneous immune cell subsets and ICI efficacy through single-cell spatial profiling of pretreatment tumor tissue, using a 29-marker multiplex IHC platform built for in-depth dissection of the TME.
RESULTS. Among various types of intratumoral lymphocytes, including Th1, Treg, and NK cells, only CD8+ T cells (tumor-infiltrating lymphocytes [TILs]) were associated with ICI efficacy. Computational tissue segmentation underscored the importance of direct physical interactions between CD8+ TILs and cancer cells for ICI efficacy. TIL phenotyping identified CD39/CD103/Ki-67 positivity as a hallmark of exhausted yet functional tumor-reactive CD8+ TILs. Immunosuppressive tumor-associated macrophages (TAMs) and cancer-associated fibroblasts were independent unfavorable adversaries. High CD73 expression on cancer cells was suggested to confer tolerance to ICI in EGFR/ALK-oncogene+ NSCLC, potentially through M2-TAM accumulation and aberrant angiogenesis.
CONCLUSION. Our study delineates the clinical relevance of heterogeneous immune cell subsets in ICI-treated mNSCLC, aiding the development of targeted therapeutic strategies. en-copyright= kn-copyright= en-aut-name=IsomotoKohsuke en-aut-sei=Isomoto en-aut-mei=Kohsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HarataniKoji en-aut-sei=Haratani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujikawaTakahiro en-aut-sei=Tsujikawa en-aut-mei=Takahiro 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=MakutaniYusuke en-aut-sei=Makutani en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakedaMasayuki en-aut-sei=Takeda en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YonesakaKimio en-aut-sei=Yonesaka en-aut-mei=Kimio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaKaoru en-aut-sei=Tanaka en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwasaTsutomu en-aut-sei=Iwasa en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=NishioKazuto en-aut-sei=Nishio en-aut-mei=Kazuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ItoAkihiko en-aut-sei=Ito en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 ORCID= affil-num=1 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=2 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Otolaryngology?Head and Neck Surgery, Kyoto Prefectural University of Medicine kn-affil= affil-num=4 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Kindai University Faculty of Medicine kn-affil= affil-num=6 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=7 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=8 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine 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=Department of Genome Biology, Kindai University Faculty of Medicine kn-affil= affil-num=12 en-affil=Department of Pathology, Kindai University Faculty of Medicine kn-affil= affil-num=13 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=5485 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260402 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bacterial collagenase harnesses collagen geometry for processive cleavage en-subtitle= kn-subtitle= en-abstract= kn-abstract=Collagen, the major structural protein in the animal extracellular matrix, forms a triple helix that resists proteolysis and requires specialised enzymes for degradation. Flesh-eating bacteria secrete collagenases that unwind the collagen triple helix and processively trim Gly?X?Y triplet repeats, yet the molecular basis of this process has remained obscure. Here, cryo-electron microscopy reveals how Hathewaya histolytica collagenase ColH engages its substrate and exploits the helixfs architecture for catalysis. ColH encircles a single collagen triple helix in a closed-ring conformation and, through dynamic domain motions, dehydrates and destabilises it. The enzyme undergoes substrate-assisted twisting to adopt a rigid ratcheted conformation, in which one chain is bent into a tripeptide-long ebightf and threaded into the active site for cleavage, while two uncut strands are partitioned to non-catalytic sites. Release of the bight appears to reset the enzyme, with the uncut strands serving as guiding tracks. Repeated cycling between dynamic and rigid states likely enables triplet-by-triplet translocation, allowing ColH to harness collagenfs geometry for processive degradation. These findings reveal a bacterial strategy for collagen unwinding and cleavage distinct from that of mammalian collagenases, highlighting divergent evolutionary solutions for degrading one of naturefs most intractable substrates. en-copyright= kn-copyright= en-aut-name=OkiHiroya en-aut-sei=Oki en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakebeKatsuki en-aut-sei=Takebe en-aut-mei=Katsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BonsuAdjoa en-aut-sei=Bonsu en-aut-mei=Adjoa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiKazunori en-aut-sei=Fujii en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasudaRyo en-aut-sei=Masuda en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HendersonNicholas en-aut-sei=Henderson en-aut-mei=Nicholas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MimaTakehiko en-aut-sei=Mima en-aut-mei=Takehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoideTakaki en-aut-sei=Koide en-aut-mei=Takaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoradiMahmoud en-aut-sei=Moradi en-aut-mei=Mahmoud kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsushitaOsamu en-aut-sei=Matsushita en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakonJoshua en-aut-sei=Sakon en-aut-mei=Joshua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawaharaKazuki en-aut-sei=Kawahara en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, The University of Osaka kn-affil= affil-num=2 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry and Biochemistry, University of Arkansas kn-affil= affil-num=4 en-affil=Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University kn-affil= affil-num=5 en-affil=Waseda Research Institute for Science and Engineering, Waseda University kn-affil= affil-num=6 en-affil=Department of Chemistry and Biochemistry, University of Arkansas kn-affil= affil-num=7 en-affil=Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences kn-affil= affil-num=8 en-affil=Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University kn-affil= affil-num=9 en-affil=Department of Chemistry and Biochemistry, University of Arkansas kn-affil= affil-num=10 en-affil=Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Chemistry and Biochemistry, University of Arkansas kn-affil= affil-num=12 en-affil=Graduate School of Pharmaceutical Sciences, The University of Osaka kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=19282 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260427 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dual-calibration RT-qPCR reveals distinct dnaK1/2/3 and groEL1/2 expression dynamics under heat and acid stress in the sinefungin producer Streptomyces incarnatus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Streptomyces incarnatus NRRL8089 produces sinefungin, a nucleoside antibiotic whose yield is enhanced under defined environmental stresses. Here, dual-calibration RT-qPCR was used to resolve paralogue-specific expression dynamics of the dnaK and groE chaperone systems under heat and acid stress conditions that increase sinefungin titres. The canonical dnaK1?dnaJ1 and groES?groEL1 operons exhibited moderate induction, whereas monocistronic paralogues (dnaK2, dnaK3 and groEL2) showed markedly higher inducibility, with up to ~?125-fold increases relative to baseline expression. Promoter analyses revealed conserved inverted repeats and differences in predicted secondary-structure stability, suggesting that promoter architecture contributes to paralogue-specific responsiveness. Structural modelling indicated divergence among DnaK paralogues in regions associated with substrate interaction, whereas GroEL paralogues retained a conserved overall scaffold, consistent with kinetic rather than structural differentiation. Together, these findings indicate that duplicated paralogues are not functionally redundant but are differentially regulated to partition proteostasis capacity under stress. This paralogue-specific regulation may provide a framework linking environmental perturbation to secondary-metabolite production in actinomycetes. en-copyright= kn-copyright= en-aut-name=Xiao-HuiZhao en-aut-sei=Xiao-Hui en-aut-mei=Zhao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuboMao en-aut-sei=Kubo en-aut-mei=Mao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamagataHaruka en-aut-sei=Yamagata en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakashimaYuriko en-aut-sei=Nakashima en-aut-mei=Yuriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HasunumaTomohisa en-aut-sei=Hasunuma en-aut-mei=Tomohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KanaoTadayoshi en-aut-sei=Kanao en-aut-mei=Tadayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TamuraTakashi en-aut-sei=Tamura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Heat shock kn-keyword=Heat shock en-keyword=Acid stress kn-keyword=Acid stress en-keyword=dnaK kn-keyword=dnaK en-keyword=hspR kn-keyword=hspR en-keyword=groES kn-keyword=groES en-keyword=groEL kn-keyword=groEL en-keyword=Sinefungin kn-keyword=Sinefungin en-keyword=Streptomyces incarnatus kn-keyword=Streptomyces incarnatus END start-ver=1.4 cd-journal=joma no-vol=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-ƒ¿?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-Barr? 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-Barr? 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=93 cd-vols= no-issue=1 article-no= start-page=e00346-2 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250131 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A newly developed oral infection mouse model of shigellosis for immunogenicity and protective efficacy studies of a candidate vaccine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Shigella infection poses a significant public health challenge in the developing world. However, lack of a widely available mouse model that replicates human shigellosis creates a major bottleneck to better understanding of disease pathogenesis and development of newer drugs and vaccines. BALB/c mice pre-treated with streptomycin and iron (FeCl3) plus desferrioxamine intraperitoneally followed by oral infection with virulent Shigella flexneri 2a resulted in diarrhea, loss of body weight, bacterial colonization and progressive colitis characterized by disruption of epithelial lining, loss of crypt architecture with goblet cell depletion, increased polymorphonuclear infiltration into the mucosa, submucosal swelling (edema), and raised proinflammatory cytokines and chemokines in the large intestine. To evaluate the usefulness of the model for vaccine efficacy studies, mice were immunized intranasally with a recombinant protein vaccine containing Shigella invasion protein invasion plasmid antigen B (IpaB). Vaccinated mice conferred protection against Shigella, indicating that the model is suitable for testing of vaccine candidates. To protect both Shigella and Salmonella, a chimeric recombinant vaccine (rIpaB?T2544) was developed by fusing IpaB with Salmonella outer membrane protein T2544. Vaccinated mice developed antigen-specific serum IgG and IgA antibodies and a balanced Th1/Th2 response and were protected against oral challenge with Shigella (S. flexneri 2a, Shigella dysenteriae, and Shigella sonnei) using our present mouse model and Salmonella (Salmonella Typhi and Paratyphi) using an iron overload mouse model. We describe here the development of an oral Shigella infection model in wild-type mouse. This model was successfully used to demonstrate the immunogenicity and protective efficacy of a candidate protein subunit vaccine against Shigella. en-copyright= kn-copyright= en-aut-name=HaldarRisha en-aut-sei=Haldar en-aut-mei=Risha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HalderProlay en-aut-sei=Halder en-aut-mei=Prolay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KoleyHemanta en-aut-sei=Koley en-aut-mei=Hemanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DasSantasabuj en-aut-sei=Das en-aut-mei=Santasabuj kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of Clinical Medicine, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=2 en-affil=Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=3 en-affil=Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=4 en-affil=Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Division of Clinical Medicine, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= en-keyword=oral route kn-keyword=oral route en-keyword=S. flexneri kn-keyword=S. flexneri en-keyword=shigellosis kn-keyword=shigellosis en-keyword=bivalent subunit vaccine (IpaB?T2544) kn-keyword=bivalent subunit vaccine (IpaB?T2544) en-keyword=mouse model kn-keyword=mouse model END start-ver=1.4 cd-journal=joma no-vol=206 cd-vols= no-issue=10 article-no= start-page=e00307-24 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Overexpression of diglucosyldiacylglycerol synthase leads to daptomycin resistance in Bacillus subtilis en-subtitle= kn-subtitle= en-abstract= kn-abstract=The lipopeptide antibiotic daptomycin exhibits bactericidal activity against Gram-positive bacteria by forming a complex with phosphatidylglycerol (PG) and lipid II in the cell membrane, causing membrane perforation. With the emergence of daptomycin-resistant bacteria, understanding the mechanisms of bacterial resistance to daptomycin has gained great importance. In this study, we aimed to identify the genetic factors contributing to daptomycin resistance in Bacillus subtilis, a model Gram-positive bacterium. Our findings demonstrated that overexpression of ugtP, which encodes diglucosyldiacylglycerol synthase, induces daptomycin resistance in B. subtilis. Specifically, overexpression of ugtP resulted in increased levels of diglucosyldiacylglycerol (Glc2DAG) and decreased levels of acidic phospholipids cardiolipin and PG, as well as the basic phospholipid lysylphosphatidylglycerol. However, ugtP overexpression did not alter the cell surface charge and the susceptibility to the cationic antimicrobial peptide nisin or the cationic surfactant hexadecyltrimethylammonium bromide. Furthermore, by serial passaging in the presence of daptomycin, we obtained daptomycin-resistant mutants carrying ugtP mutations. These mutants showed increased levels of Glc2DAG and a >4-fold increase in the minimum inhibitory concentration of daptomycin. These results suggest that increased Glc2DAG levels, driven by ugtP overexpression, modify the phospholipid composition and confer daptomycin resistance in B. subtilis without altering the cell surface charge of the bacteria. en-copyright= kn-copyright= en-aut-name=YamamotoRyogo en-aut-sei=Yamamoto en-aut-mei=Ryogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshikawaKazuya en-aut-sei=Ishikawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyoshiYusuke en-aut-sei=Miyoshi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FurutaKazuyuki en-aut-sei=Furuta en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyoshiShin-Ichi en-aut-sei=Miyoshi en-aut-mei=Shin-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KaitoChikara en-aut-sei=Kaito en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=diglucosyldiacylglycerol kn-keyword=diglucosyldiacylglycerol en-keyword=daptomycin kn-keyword=daptomycin en-keyword=phospholipid kn-keyword=phospholipid END start-ver=1.4 cd-journal=joma no-vol=171 cd-vols= no-issue=1 article-no= start-page=18 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=Novel Escherichia coli phages representing a distinct genus within the subfamily Stephanstirmvirinae: genome and host range characteristics en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bacteriophages play crucial roles in microbial ecosystems and have potential for biotechnological applications. However, our understanding of culturable phages remains limited. In this study, we characterized six novel Escherichia coli phages isolated from pig farm wastewater and urban sewage, using comprehensive genomic, morphological, and host-range analysis. Using multiple comparative approaches, including gene-sharing network analysis, average nucleotide identity (ANI), and nucleotide intergenomic similarity (NIS), we demonstrated that five of these phages form a distinct group within the subfamily Stephanstirmvirinae, potentially representing a novel genus, for which we propose the name "Wecvirush. We further propose that these phages, each of which exhibits a unique host range pattern, should be classified in two distinct species within the proposed genus. This host specificity is reflected in differences in the amino acid sequences of tail fibers, which are crucial for infection. The remaining phage, which was not classified as a wecvirus, exhibited characteristics that challenged the current classification criteria, highlighting the need for more-flexible taxonomic approaches. These findings expand our understanding of phage diversity within the subfamily Stephanstirmvirinae and contribute to the evolving phage taxonomy framework. en-copyright= kn-copyright= en-aut-name=KanekoTomoyoshi en-aut-sei=Kaneko en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OsakaToshifumi en-aut-sei=Osaka en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsunedaSatoshi en-aut-sei=Tsuneda en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Life Science and Medical Bioscience, Waseda University kn-affil= affil-num=2 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Microbiology and Immunology, Tokyo Womenfs Medical University kn-affil= affil-num=4 en-affil=Department of Life Science and Medical Bioscience, Waseda University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=16 article-no= start-page=1886 end-page=1897 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Methotrexate, Doxorubicin, and Cisplatin Versus Methotrexate, Doxorubicin, and Cisplatin + Ifosfamide in Poor Responders to Preoperative Chemotherapy for Newly Diagnosed High-Grade Osteosarcoma (JCOG0905): A Multicenter, Open-Label, Randomized Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Our previous NECO phase II studies on high-grade osteosarcoma suggested that administering ifosfamide (IF; 16 g/m2 [4g/m2 once on day 1, then 2g/m2 once on days 2-7] ~ six) to patients showing a poor response (PrRsp) to preoperative chemotherapy with methotrexate, doxorubicin, and cisplatin (MAP) improves their prognoses. In this Japan Clinical Oncology Group (JCOG) study, JCOG0905, we aimed to investigate the efficacy and safety of IF in patients with PrRsp.
Methods JCOG0905 is a multicenter, open-label, multi-institutional, randomized trial. Eligible patients (50 years and younger) had resectable, high-grade osteosarcoma (stage II or III, Union for International Cancer Control TNM) of the extremities, limb girdles, and thoracic wall. After two MAP cycles and tumor resection, patients with PrRsp were randomly assigned to either the MAP or MAP plus 15 g/m2 (3g/m2 once daily on days 1-5) ~ six IF (MAP + IF [MAPIF]) group. The primary end point was disease-free survival (DFS); secondary end points were overall survival (OS) and safety. The planned sample size was 100 patients with a one-sided ƒ¿ of .1 and a power of 0.7, assuming a 3-year DFS of 50% and 65% for MAP and MAPIF, respectively. This trial is registered with the Japan Registry of Clinical Trials (jRCT; jRCTs031180126).
Results Of the 287 patients registered between February 2010 and August 2020, 51 and 52 patients with PrRsp were assigned to the MAP and MAPIF groups, respectively. As of March 2022, DFS did not differ between groups (hazard ratio [HR], 1.05 [95% CI, 0.55 to 1.98]) and OS was numerically inferior in the MAPIF group (HR, 1.48 [95% CI, 0.68 to 3.22]). Nine and zero patients in the MAPIF and MAP groups discontinued treatment because of adverse events, respectively.
Conclusion Evidence from JCOG0905 does not support the addition of IF for patients with PrRsp. en-copyright= kn-copyright= en-aut-name=HiragaHiroaki en-aut-sei=Hiraga en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MachidaRyunosuke en-aut-sei=Machida en-aut-mei=Ryunosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaiAkira en-aut-sei=Kawai en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YonemotoTsukasa en-aut-sei=Yonemoto en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EndoMakoto en-aut-sei=Endo en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishidaYoshihiro en-aut-sei=Nishida en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NaganoAkihito en-aut-sei=Nagano en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AeKeisuke en-aut-sei=Ae en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshidaShinichirou en-aut-sei=Yoshida en-aut-mei=Shinichirou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsanumaKunihiro en-aut-sei=Asanuma en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ToguchidaJunya en-aut-sei=Toguchida en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FurutaTaisuke en-aut-sei=Furuta en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakayamaRobert en-aut-sei=Nakayama en-aut-mei=Robert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AkisueToshihiro en-aut-sei=Akisue en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HirumaToru en-aut-sei=Hiruma en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MoriiTakeshi en-aut-sei=Morii en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NishimuraHideki en-aut-sei=Nishimura en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HiraokaKoji en-aut-sei=Hiraoka en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakeyamaMasanobu en-aut-sei=Takeyama en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=EmoriMakoto en-aut-sei=Emori en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=TsukushiSatoshi en-aut-sei=Tsukushi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HatanoHiroshi en-aut-sei=Hatano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KawashimaHiroyuki en-aut-sei=Kawashima en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=IsuKazuo en-aut-sei=Isu en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=TanakaKazuhiro en-aut-sei=Tanaka en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KataokaTomoko en-aut-sei=Kataoka en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=FukudaHaruhiko en-aut-sei=Fukuda en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=IwamotoYukihide en-aut-sei=Iwamoto en-aut-mei=Yukihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Musculoskeletal Oncology, NHO Hokkaido Cancer Center kn-affil= affil-num=2 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=3 en-affil=Musculoskeletal Oncology, National Cancer Center Hospital kn-affil= affil-num=4 en-affil=Orthopaedic Surgery, Faculty of Medicine, Okayama University kn-affil= affil-num=5 en-affil=Orthopaedic Surgery, Chiba Cancer Center kn-affil= affil-num=6 en-affil=Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=7 en-affil=Department of Rehabilitation Medicine, Nagoya University Hospital kn-affil= affil-num=8 en-affil=Orthopaedic Surgery, Gifu University School of Medicine kn-affil= affil-num=9 en-affil=Orthopaedic Surgery, Cancer Institute Hospital kn-affil= affil-num=10 en-affil=Orthopaedic Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Orthopaedic Surgery, Mie University kn-affil= affil-num=12 en-affil=Department of Tissue Regeneration, Center for Induced Pluripotent Stem Cell Research and Application, Institute for Frontier Medical Sciences, Kyoto University kn-affil= affil-num=13 en-affil=Orthopaedic Surgery, Hiroshima University kn-affil= affil-num=14 en-affil=Department of Orthopaedic Surgery, Keio University School of Medicine kn-affil= affil-num=15 en-affil=Orthopaedic Surgery, Kobe University kn-affil= affil-num=16 en-affil=Bone and Soft Tissue Tumour Surgery, Kanagawa Cancer Center kn-affil= affil-num=17 en-affil=Orthopaedic Surgery, Kyorin University kn-affil= affil-num=18 en-affil=Orthopaedic Surgery, Kagawa University Hospital kn-affil= affil-num=19 en-affil=Orthopaedic Surgery, Kurume University Hospital kn-affil= affil-num=20 en-affil=Orthopaedic Surgery, Yokohama City University Hospital kn-affil= affil-num=21 en-affil=Orthopaedic Surgery, Sapporo Medical University Hospital kn-affil= affil-num=22 en-affil=Orthopaedic Surgery, Aichi Cancer Center kn-affil= affil-num=23 en-affil=Musculoskeletal Oncology, Niigata Cancer Center Hospital kn-affil= affil-num=24 en-affil=Orthopaedic Surgery, Niigata University Medical & Dental Hospital kn-affil= affil-num=25 en-affil=Orthopaedic Surgery, Higashi Sapporo Hospital kn-affil= affil-num=26 en-affil=Advanced Medical Sciences, Oita University Faculty of Medicine kn-affil= affil-num=27 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=28 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=29 en-affil=Orthopaedic Surgery, Kyushu Rosai Hospital kn-affil= affil-num=30 en-affil=Orthopaedic Surgery, Faculty of Medicine, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=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=46 cd-vols= no-issue=10 article-no= start-page=1643 end-page=1652 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240809 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Radiological assessment of the dissection area in supraomohyoid neck dissection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose The current supraomohyoid neck dissection (SOHND) is performed above the omohyoid muscle to dissect levels I, II, and III in the levels of cervical lymph nodes. However, the anatomical boundary between levels III and IV is the inferior border of the cricoid cartilage. We investigated the anatomical relationship between the omohyoid muscle and cricoid cartilage using contrast-enhanced CT (CE-CT) images to assess the validity of the current SOHND.
Methods CE-CT images of the head and neck regions in patients were reviewed. The patients were divided into two groups: gmalignant tumorsh and gothersh. The vertebral levels corresponding to the positions of anatomical structures such as the intersection of the omohyoid muscle and internal jugular vein (OM-IJ), and the inferior border of the cricoid cartilage (CC), were recorded.
Results The OM-IJ was located around the seventh cervical to the first thoracic vertebra. There was a significant difference between the malignant tumor and others groups in females (p?=?0.036). The CC was located around the sixth to seventh cervical vertebrae. There was a significant sex difference in each group (malignant tumor: p? Conclusion This study provides clear anatomical evidence showing the difference between the SOHND dissection area and levels I, II, and III. It could be considered that in most cases SOHND invades level IV, not just levels I, II, and III, especially in female patients. en-copyright= kn-copyright= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhyamaYoshio en-aut-sei=Ohyama en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsushitaYuki en-aut-sei=Matsushita en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TubbsR. Shane en-aut-sei=Tubbs en-aut-mei=R. Shane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KitagawaNorio en-aut-sei=Kitagawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawazuToshiyuki en-aut-sei=Kawazu en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HisatomiMiki en-aut-sei=Hisatomi en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkadaShunsuke en-aut-sei=Okada en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujikuraMamiko en-aut-sei=Fujikura en-aut-mei=Mamiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AsaumiJunichi en-aut-sei=Asaumi en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Clinical Anatomy Research Association in Oral and Maxillofacial Surgery kn-affil= affil-num=3 en-affil=Clinical Anatomy Research Association in Oral and Maxillofacial Surgery kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Clinical Anatomy Research Association in Oral and Maxillofacial Surgery kn-affil= affil-num=6 en-affil=Clinical Anatomy Research Association in Oral and Maxillofacial Surgery kn-affil= affil-num=7 en-affil=Clinical Anatomy Research Association in Oral and Maxillofacial Surgery kn-affil= affil-num=8 en-affil= kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Anatomy kn-keyword=Anatomy en-keyword=Omohyoid muscle kn-keyword=Omohyoid muscle en-keyword=Computed tomography kn-keyword=Computed tomography en-keyword=Neck dissection kn-keyword=Neck dissection en-keyword=Vertebra kn-keyword=Vertebra en-keyword=Cancer kn-keyword=Cancer END start-ver=1.4 cd-journal=joma no-vol=100 cd-vols= no-issue=1 article-no= start-page=66 end-page=77 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Different impacts of granulocyte colony]stimulating factor administration on allogeneic hematopoietic cell transplant outcomes for adult acute myeloid leukemia according to graft type en-subtitle= kn-subtitle= en-abstract= kn-abstract=We retrospectively evaluated the impacts of using granulocyte colony-stimulating factor (G-CSF) and its timing on posttransplant outcomes for 9766 adults with acute myeloid leukemia (AML) between 2013 and 2022 using a Japanese database. We separately evaluated three distinct cohorts based on graft type: 3248 received bone marrow transplantation (BMT), 3066 received peripheral blood stem cell transplantation (PBSCT), and 3452 received single-unit cord blood transplantation (CBT). Multivariate analysis showed that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT. However, it was associated with a higher risk of grades II?IV acute graft-versus-host disease (GVHD) across all graft types. Moreover, an increased incidence of overall chronic GVHD was observed with G-CSF administration in BMT and CBT patients, but not in PBSCT patients. G-CSF administration significantly improved overall survival (OS) and leukemia-free survival (LFS) only following CBT. Regarding the timing of G-CSF, in comparison with late initiation of G-CSF (Days 5?10), early initiation (Days 0?4) did not provide benefits for hematopoietic recovery regardless of graft type. In contrast, late initiation was significantly associated with a lower risk of grades II?IV acute GVHD and better OS and LFS in CBT patients. These data demonstrated that G-CSF administration accelerated neutrophil recovery and increased the risk of grades II?IV acute GVHD across all graft types, but significantly improved survival outcomes but only following CBT. Therefore, routine use of G-CSF should be considered for CBT in adult patients with AML. en-copyright= kn-copyright= en-aut-name=KonumaTakaaki en-aut-sei=Konuma en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KamedaKazuaki en-aut-sei=Kameda en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoritaKaoru en-aut-sei=Morita en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoTadakazu en-aut-sei=Kondo en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimuraFumihiko en-aut-sei=Kimura en-aut-mei=Fumihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=OuchiFumihiko en-aut-sei=Ouchi en-aut-mei=Fumihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchidaNaoyuki en-aut-sei=Uchida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaMasatsugu en-aut-sei=Tanaka en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishidaTetsuya en-aut-sei=Nishida en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 ORCID= en-aut-name=Sakata]YanagimotoMamiko en-aut-sei=Sakata]Yanagimoto en-aut-mei=Mamiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=SawaMasashi en-aut-sei=Sawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 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=17 ORCID= en-aut-name=FujiwaraShin]Ichiro en-aut-sei=Fujiwara en-aut-mei=Shin]Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 ORCID= en-aut-name=IshimaruFumihiko en-aut-sei=Ishimaru en-aut-mei=Fumihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YoshimitsuMakoto en-aut-sei=Yoshimitsu en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KandaYoshinobu en-aut-sei=Kanda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=OhbikiMarie en-aut-sei=Ohbiki en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 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=24 ORCID= en-aut-name=YanadaMasamitsu en-aut-sei=Yanada en-aut-mei=Masamitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= affil-num=1 en-affil=Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo kn-affil= affil-num=2 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Center kn-affil= affil-num=3 en-affil=Division of Hematology, Jichi Medical University kn-affil= affil-num=4 en-affil=Department of Hematology, Kobe City Medical Center General Hospital kn-affil= affil-num=5 en-affil=Division of Hematology, Department of Internal Medicine, National Defense Medical College kn-affil= affil-num=6 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Center kn-affil= affil-num=7 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Toranomon Hospital kn-affil= affil-num=9 en-affil=Department of Hematology, Kanagawa Cancer Center kn-affil= affil-num=10 en-affil=Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital kn-affil= affil-num=11 en-affil=Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital kn-affil= affil-num=12 en-affil=Department of Hematology, Hokkaido University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology, University of Tsukuba Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Tokai University School of Medicine kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Anjo Kosei Hospital kn-affil= affil-num=16 en-affil=Department of Hematology, Sapporo Hokuyu Hospital kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=18 en-affil=Division of Hematology, Jichi Medical University kn-affil= affil-num=19 en-affil=Department of Hematology, Hyogo Medical University Hospital kn-affil= affil-num=20 en-affil=Technical Department, Japanese Red Cross Society Blood Service Headquarters kn-affil= affil-num=21 en-affil=Department of Hematology and Rheumatology, Kagoshima University Hospital kn-affil= affil-num=22 en-affil=Division of Hematology, Jichi Medical University kn-affil= affil-num=23 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=24 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=25 en-affil=Department of Hematology and Oncology, Nagoya City University East Medical Center kn-affil= END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=2 article-no= start-page=18 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250418 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The effect of Fe incorporation on the single-crystal elasticity of ƒÂ-AlOOH en-subtitle= kn-subtitle= en-abstract= kn-abstract=The seismic mapping of hydrous materials in the Earthfs deep interior requires experimental constraints on the elastic anisotropy of hydrous minerals and phases. Oxyhydroxides like ƒÂ-(Al,Fe)OOH are arguably the main hosts of water in the lower mantle. Therefore, constraints on the single-crystal elastic tensor of ƒÂ-(Al,Fe)OOH solid solutions are crucial to quantify the elastic anisotropy of this material, and advance the current understanding of the recycling of water into the lower mantle. Yet, experimental data for intermediate compositions are scarce, limiting the understanding of how Fe incorporation affects the single-crystal elastic properties of ƒÂ-AlOOH. In this study, we provide experimental constraints on the single-crystal elasticity of two ƒÂ-(Al,Fe)OOH solid solutions, with Fe/(Al?+?Fe) of 0.06(1) and 0.133(3). Large single-crystal samples of ƒÂ-(Al,Fe)OOH were synthetized at high pressures and temperatures using a multi-anvil press, and the full elastic stiffness tensors were determined at ambient conditions by combining X-ray diffraction and Brillouin scattering measurements. We show that replacing Al3+ with Fe3+ in ƒÂ-(Al,Fe)OOH lowers the magnitude of most coefficients of the elastic stiffness tensor (cij), which translates into a substantial reduction of aggregate moduli and acoustic wave velocities. We further show that, at ambient conditions, the acoustic anisotropy of ƒÂ-(Al,Fe)OOH displays no sensitivity to Fe?Al substitution. en-copyright= kn-copyright= en-aut-name=SattaNiccol? en-aut-sei=Satta en-aut-mei=Niccol? kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=CrinitiGiacomo en-aut-sei=Criniti en-aut-mei=Giacomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Boffa BallaranTiziana en-aut-sei=Boffa Ballaran en-aut-mei=Tiziana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KurnosovAlexander en-aut-sei=Kurnosov en-aut-mei=Alexander kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BuchenJohannes en-aut-sei=Buchen en-aut-mei=Johannes kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MarquardtHauke en-aut-sei=Marquardt en-aut-mei=Hauke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Institut f?r Mineralogie, Universit?t M?nster kn-affil= affil-num=2 en-affil=Bayerisches Geoinstitut, Universit?t Bayreuth kn-affil= affil-num=3 en-affil=Bayerisches Geoinstitut, Universit?t Bayreuth kn-affil= affil-num=4 en-affil=Bayerisches Geoinstitut, Universit?t Bayreuth kn-affil= affil-num=5 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=6 en-affil=Bayerisches Geoinstitut, Universit?t Bayreuth kn-affil= affil-num=7 en-affil=Department of Earth Sciences, University of Oxford kn-affil= en-keyword=Elasticity kn-keyword=Elasticity en-keyword=ƒÂ-AlOOH kn-keyword=ƒÂ-AlOOH en-keyword=Water kn-keyword=Water en-keyword=Anisotropy kn-keyword=Anisotropy en-keyword=Solid solutions kn-keyword=Solid solutions en-keyword=Brillouin scattering kn-keyword=Brillouin scattering END start-ver=1.4 cd-journal=joma no-vol=361 cd-vols= no-issue= article-no= start-page=107331 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of chemistry on the compressibility and high-pressure structural evolution of the CaFe2O4-type aluminous silicate phase en-subtitle= kn-subtitle= en-abstract= kn-abstract=Approximately 22?26 vol% of a basaltic phase assemblage at lower mantle conditions is comprised of a (Na,Mg,Fe2+)(Al,Si,Fe3+)2O4 phase with CaFe2O4-type (CF-type) structure. Previous experimental studies attempted to determine the equation of state of the CF-type phase but reported contrasting compressibility values, even for samples with the same composition. Therefore, the elastic properties of the CF-type phase remain, to date, largely unconstrained. Here, we conducted single-crystal X-ray diffraction (SCXRD) measurements in the diamond anvil cell (DAC) at high pressure and room temperature on three samples of CF-type phase with compositions Na0.90(1)Al1.03(2)Si1.00(2)O4 (NaCF), Na0.66(4)Mg0.28(4)Al1.22(3)Si0.78(3)O4 (MgCF) and Na0.62(2)Mg0.19(1)Fe2+0.17(1)Fe3+0.080(4)Al1.20(3)Si0.70(1)O4 (FeCF). A multi-sample loading approach was employed for most DAC runs, where two samples were loaded in the same sample chamber to reduce possible systematic deviations between datasets, thus enhancing internal consistency and corroborating data reproducibility. Experiments on the NaCF and MgCF samples were conducted up to ?50 GPa, while the FeCF sample was compressed to ?72 GPa to better characterize the effect of the spin crossover of octahedrally coordinated Fe3+. We found the isothermal bulk modulus (KT0) to increase with decreasing NaAlSiO4 content, accompanied by only a slight decrease in its pressure derivative (K'T0). Analysis of the crystal structures of the three samples at high pressure allowed compositional trends to be determined also for the interatomic bonds and polyhedral compressibility, as well as the distortion indices. These suggest an overall stiffening of the A site with increasing Mg2+ and Fe2+ content, as well of the two B sites with increasing Al3+ and Fe3+ content. Enhanced compressibility of the unit cell and octahedral B sites was observed between ?26?42 GPa in the FeCF sample, suggesting a pressure-induced spin crossover of Fe3+, in agreement with some previous observations. Finally, trends in the elastic properties from experimental studies conducted along the NaAlSiO4-MgAl2O4 join are discussed and used as a proxy to evaluate the reliability of end-member properties for the CF-type phase employed in most recent mineral physical and thermodynamic databases. Our analysis suggests current mineral physical models might underestimate densities and overestimate bulk sound velocities of NaAlSiO4-rich CF-type phases with basaltic composition. en-copyright= kn-copyright= en-aut-name=CrinitiGiacomo en-aut-sei=Criniti en-aut-mei=Giacomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Boffa BallaranTiziana en-aut-sei=Boffa Ballaran en-aut-mei=Tiziana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurnosovAlexander en-aut-sei=Kurnosov en-aut-mei=Alexander kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RogmannElena-Marie en-aut-sei=Rogmann en-aut-mei=Elena-Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GlazyrinKonstantin en-aut-sei=Glazyrin en-aut-mei=Konstantin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FedotenkoTimofey en-aut-sei=Fedotenko en-aut-mei=Timofey kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FrostDaniel J. en-aut-sei=Frost en-aut-mei=Daniel J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=2 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=3 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=4 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=5 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= affil-num=6 en-affil=Deutsches Elektronen-Synchrotron DESY kn-affil= affil-num=7 en-affil=Deutsches Elektronen-Synchrotron DESY kn-affil= affil-num=8 en-affil=Bayerisches Geoinstitut, University of Bayreuth kn-affil= en-keyword=CaFe2O4-type phase kn-keyword=CaFe2O4-type phase en-keyword=Lower mantle kn-keyword=Lower mantle en-keyword=Equations of state kn-keyword=Equations of state en-keyword=Structural refinements kn-keyword=Structural refinements en-keyword=Crystal chemistry kn-keyword=Crystal chemistry en-keyword=Fe3+ spin-crossover kn-keyword=Fe3+ spin-crossover END start-ver=1.4 cd-journal=joma no-vol=59 cd-vols= no-issue=12 article-no= start-page=3282 end-page=3304 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241027 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Radial transport and nebular thermal processing of millimeter]sized solids in the Solar protoplanetary disk inferred from Cr]Ti]O isotope systematics of chondrules en-subtitle= kn-subtitle= en-abstract= kn-abstract=Understanding the material transport and mixing processes in the Solar protoplanetary disk provides important constraints on the origin of chemical and isotopic diversities of our planets. The limited extent of radial transport and mixing between the inner and outer Solar System has been suggested based on a fundamental isotopic dichotomy between non-carbonaceous (NC) and carbonaceous (CC) meteorite groups. The limited transport and mixing could be further tested by tracing the formation regions of individual meteoritic components, such as Ca-Al-rich inclusions (CAIs) and chondrules. Here, we show further evidence for the outward transport of CAIs and chondrules from the inner and subsequent thermal processing in the outer region of the protoplanetary disk based on the petrography and combined Cr-Ti-O isotope systematics of chondrules from the Vigarano-like (CV) carbonaceous chondrite Allende. One chondrule studied consists of an olivine core that exhibits NC-like Ti and O, but CC-like Cr isotopic signatures, which is enclosed by a pyroxene igneous rim with CC-like O isotope ratios. These observations indicate that the olivine core formed in the inner Solar System. The olivine core then migrated into the outer Solar System and experienced nebular thermal processing that generated the pyroxene igneous rim. The nebular thermal processing would result in Cr isotope exchange between the olivine core and CC-like materials, but secondary alteration effects on the parent body are also responsible for the CC-like Cr isotope signature. By combining previously reported Cr-Ti-O isotope systematics of CV chondrules, we show that some CV chondrules larger than ~1?mm would have formed in the inner Solar System. The accretion of the millimeter-sized, inner Solar System solids onto the CV carbonaceous chondrite parent body would require their very early migration into the outer Solar System within the first 1 million years after the Solar System formation. en-copyright= kn-copyright= en-aut-name=FukudaKohei en-aut-sei=Fukuda en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HibiyaYuki en-aut-sei=Hibiya en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KastelleCraig R. en-aut-sei=Kastelle en-aut-mei=Craig R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiKatsuhiko en-aut-sei=Suzuki en-aut-mei=Katsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IizukaTsuyoshi en-aut-sei=Iizuka en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamashitaKatsuyuki en-aut-sei=Yamashita en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HelserThomas E. en-aut-sei=Helser en-aut-mei=Thomas E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KitaNoriko T. en-aut-sei=Kita en-aut-mei=Noriko T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=WiscSIMS, Department of Geoscience, University of Wisconsin-Madison kn-affil= affil-num=2 en-affil=Research Center for Advanced Science and Technology, Graduate School of Science, The University of Tokyo kn-affil= affil-num=3 en-affil=National Oceanic and Atmospheric Administration kn-affil= affil-num=4 en-affil=Submarine Resources Research Center, Japan Agency for Marine-Earth Science Technology kn-affil= affil-num=5 en-affil=Department of Earth and Planetary Science, Graduate School of Science, The University of Tokyo 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=National Oceanic and Atmospheric Administration kn-affil= affil-num=8 en-affil=WiscSIMS, Department of Geoscience, University of Wisconsin-Madison kn-affil= END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=3 article-no= start-page=497 end-page=503 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Five-year outcomes with gefitinib induction and chemoradiotherapy in EGFR-mutant stage III non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background We previously showed the 2-year OS rate, the primary endpoint, of 90% in a phase II trial of gefitinib induction followed by chemoradiotherapy (CRT) in unresectable, stage III, EGFR-mutant, non-small-cell lung cancer (NSCLC). However, neither long-term survival data nor late-phase adverse event profiles have been presented.
Patients and methods Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy for 8 weeks. After confirming no disease progression during induction therapy, cisplatin and docetaxel on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy were subsequently administered.
Results In the enrolled twenty patients, the 5-year OS rate and median survival time were 70.0% [95% confidence interval: 45.1?85.3] and 5.5 years [4.91-NE], respectively, whereas 5-year PFS rate and median PFS time were 15.0% (3.7?33.5) and 1.4 years [0.69?2.29], respectively. Efficacy did not seem influenced even if radiation field was re-planed in response to the effect of gefitinib induction. As for late adverse events, pulmonary fibrosis occurred in 7 patients (35%). The median time from completion of CRT to the occurrence of the event was 245 days. All were grade 1, and there was no evidence of cavitation of the lesions or chronic infections such as Aspergillus infection during the course of the disease. One case of small cell lung cancer occurred during the period.
Conclusions With longer follow-up time, we demonstrated favorable efficacy with tolerable toxicity profiles in the EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III, NSCLC.
Trial registration numbers UMIN00005086. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000006047&type=summary&language=EjRCTs071180036. https://jrct.niph.go.jp/latest-detail/jRCTs071180036 en-copyright= kn-copyright= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaekiSho en-aut-sei=Saeki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakataShinya en-aut-sei=Sakata en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamaguchiMasafumi en-aut-sei=Yamaguchi en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaradaDaijiro en-aut-sei=Harada en-aut-mei=Daijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BesshoAkihiro en-aut-sei=Bessho en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaKentaro en-aut-sei=Tanaka en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InoueKoji en-aut-sei=Inoue en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=InoueKoji en-aut-sei=Inoue en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GembaKenichi en-aut-sei=Gemba en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SatoAkiko en-aut-sei=Sato en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=WatanabeHiromi en-aut-sei=Watanabe en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KishimotoJunji en-aut-sei=Kishimoto en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShioyamaYoshiyuki en-aut-sei=Shioyama en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KatsuiKuniaki en-aut-sei=Katsui en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SugioKenji en-aut-sei=Sugio en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Kumamoto University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Kumamoto University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic Oncology, NHO Kyushu Cancer Center kn-affil= affil-num=5 en-affil=Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Kyushu University Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Kitakyushu Municipal Medical Center kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Chugoku Central Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=16 en-affil=Radiation Oncology, Ion Beam Therapy Center, SAGA HIMAT Foundation kn-affil= affil-num=17 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=18 en-affil=Division of Radiation Oncology, Department of Thoracic and Breast Surgery, Oita University kn-affil= affil-num=19 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=Non-small-cell lung cancer kn-keyword=Non-small-cell lung cancer en-keyword=Locally advanced setting kn-keyword=Locally advanced setting en-keyword=Chemoradiation kn-keyword=Chemoradiation en-keyword=Epidermal growth factor receptor kn-keyword=Epidermal growth factor receptor END start-ver=1.4 cd-journal=joma no-vol= 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=208 cd-vols= no-issue=5 article-no= start-page=e00103-26 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=Knockout of tusA confers cationic antimicrobial resistance via fur and omp genes in Escherichia coli en-subtitle= kn-subtitle= en-abstract= kn-abstract=tRNA 2-thiouridine synthesizing protein A (TusA), a sulfur-carrier protein, plays a crucial role in tRNA sulfur modification. Several studies have reported that tusA deficiency affects iron?sulfur (Fe?S) homeostasis in addition to tRNA sulfur modification, resulting in pleiotropic phenotypes. In this study, we analyzed the phenotype of tusA-deficient Escherichia coli and its underlying mechanisms. Although the Keio tusA knockout strain showed increased swimming motility and flagellar biosynthesis, these phenotypes were not restored by tusA complementation. Genome resequencing of the original Keio tusA knockout strain identified an unintended secondary mutation in lrhA, a transcriptional regulator of flagellar and chemotaxis genes. This secondary mutation impaired lrhA function, contributing to enhanced flagellar synthesis and swimming motility, as well as altered global gene expression. A tusA knockout strain in which the secondary mutation was corrected (ĢtusA) exhibited reduced swimming motility compared with the wild-type strain, despite showing no abnormalities in flagellar formation. Furthermore, ĢtusA displayed increased resistance to cationic antibacterial agents, including cetyltrimethylammonium bromide, cetylpyridinium chloride, and protamine sulfate. The reduced motility caused by tusA deletion was observed independently of Fur, a global regulator of iron homeostasis, whereas resistance to cationic antibacterial agents was abolished in the fur knockout background. In addition, altered expression of outer membrane protein (omp) genes was observed in ĢtusA, and deletion of these omp genes abolished resistance to cationic antibacterial agents. Together, these results indicate that, by disentangling the phenotypic effects of tusA deletion from those of the unintended secondary mutation, loss of tusA confers resistance to cationic antibacterial agents through a Fur-dependent and Omp-dependent mechanism. en-copyright= kn-copyright= en-aut-name=IshikawaKazuya en-aut-sei=Ishikawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakataKiho en-aut-sei=Nakata en-aut-mei=Kiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaKoichiro en-aut-sei=Yamada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UnemeMio en-aut-sei=Uneme en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FurutaKazuyuki en-aut-sei=Furuta en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KaitoChikara en-aut-sei=Kaito en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=tusA kn-keyword=tusA en-keyword=fur kn-keyword=fur en-keyword=Escherichia coli kn-keyword=Escherichia coli en-keyword=cationic antimicrobial agents kn-keyword=cationic antimicrobial agents END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=2 article-no= start-page=215 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250218 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Review on the Magnetovolume Effect of the Full Heusler Alloys Ni2MnZ (Z = In, Sn, Sb) en-subtitle= kn-subtitle= en-abstract= kn-abstract=The full Heusler alloys Ni2MnZ (Z = In, Sn, Sb) exhibit ferromagnetic properties with a Curie temperature (TC) above room temperature. The magnetic properties of Ni2MnZ (Z = In, Sn, Sb) were studied through a combination of experiments and band calculations under ambient and elevated pressures. The main results of this study open up further prospects for controlling the magnetic properties of the multifunctional Heusler alloys Ni2Mn1+xZ1?x (Z = In, Sn, Sb) and their practical application. en-copyright= kn-copyright= en-aut-name=KanomataTakeshi en-aut-sei=Kanomata en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=XuXiao en-aut-sei=Xu en-aut-mei=Xiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakonTakuo en-aut-sei=Sakon en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagataYuki en-aut-sei=Nagata en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImadaShin en-aut-sei=Imada en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriToshihiro en-aut-sei=Omori en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KainumaRyosuke en-aut-sei=Kainuma en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=EtoTetsujiro en-aut-sei=Eto en-aut-mei=Tetsujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AdachiYoshiya en-aut-sei=Adachi en-aut-mei=Yoshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KiharaTakumi en-aut-sei=Kihara en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AmakoYasushi en-aut-sei=Amako en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DoiMasaaki en-aut-sei=Doi en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UwatokoYoshiya en-aut-sei=Uwatoko en-aut-mei=Yoshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Research Institute for Engineering and Technology, Tohoku Gakuin University kn-affil= affil-num=2 en-affil=Department of Materials Science, Graduate School of Engineering, Tohoku University kn-affil= affil-num=3 en-affil=Faculty of Advanced Science and Technology, Ryukoku University kn-affil= affil-num=4 en-affil=Faculty of Advanced Science and Technology, Ryukoku University kn-affil= affil-num=5 en-affil=College of Science and Engineering, Ritsumeikan University kn-affil= affil-num=6 en-affil=Department of Materials Science, Graduate School of Engineering, Tohoku University kn-affil= affil-num=7 en-affil=Department of Materials Science, Graduate School of Engineering, Tohoku University kn-affil= affil-num=8 en-affil=Kurume Institute of Technology kn-affil= affil-num=9 en-affil=Graduate School of Science and Technology, Yamagata University kn-affil= affil-num=10 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=11 en-affil=Faculty of Science, Shinshu University kn-affil= affil-num=12 en-affil=Research Institute for Engineering and Technology, Tohoku Gakuin University kn-affil= affil-num=13 en-affil=Institute for Solid State Physics, The University of Tokyo kn-affil= en-keyword=magnetovolume effect kn-keyword=magnetovolume effect en-keyword=magnetic properties kn-keyword=magnetic properties en-keyword=pressure effect kn-keyword=pressure effect en-keyword=itinerant electron magnets kn-keyword=itinerant electron magnets en-keyword=Heusler alloys kn-keyword=Heusler alloys END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=3239 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Low melt viscosity enables melt doublets above the 410-km discontinuity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Seismic and magnetotelluric studies suggest hydrous silicate melts atop the 410?km discontinuity form 30?100?km thick layers. Importantly, in some regions, two layers are observed. These stagnant layers are related to their comparable density to the surrounding mantle, but their formation mechanisms and detailed structures remain unclear. Here we report a large decrease of silicate melt viscosity at ~14?GPa, from 96(5) to 11.7(6) mPa?s, as water content increases from 15.5 to 31.8?mol% H?O. Such low viscosities facilitate rapid segregation of melt, which would typically prevent thick layer accumulation. Our 1D finite element simulations show that continuous dehydration melting of upwelling mantle material produces a primary melt layer above 410?km and a secondary layer at the depth of equal mantle-melt densities. These layers can merge into a single thick layer under low density contrasts or high upwelling rates, explaining both melt doublets and thick single layers. en-copyright= kn-copyright= en-aut-name=XieLongjian en-aut-sei=Xie en-aut-mei=Longjian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AndraultDenis en-aut-sei=Andrault en-aut-mei=Denis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=HanCunrui en-aut-sei=Han en-aut-mei=Cunrui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HammondJames O. S. en-aut-sei=Hammond en-aut-mei=James O. S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=XuFang en-aut-sei=Xu en-aut-mei=Fang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhaoBin en-aut-sei=Zhao en-aut-mei=Bin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LordOliver T. en-aut-sei=Lord en-aut-mei=Oliver T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=FalvardSimon en-aut-sei=Falvard en-aut-mei=Simon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KakizawaSho en-aut-sei=Kakizawa en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TsujinoNoriyoshi en-aut-sei=Tsujino en-aut-mei=Noriyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HigoYuji en-aut-sei=Higo en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HenryLaura en-aut-sei=Henry en-aut-mei=Laura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=GuignotNicolas en-aut-sei=Guignot en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=DobsonDavid P. en-aut-sei=Dobson en-aut-mei=David P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Center for High Pressure Science & Technology Advanced Research kn-affil= affil-num=2 en-affil=Universit? Clermont Auvergne, CNRS, IRD, OPGC, Laboratoire Magmas et Volcans kn-affil= affil-num=3 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=4 en-affil=School of Natural Sciences, Birkbeck, University of London kn-affil= affil-num=5 en-affil=School of Natural Sciences, Birkbeck, University of London kn-affil= affil-num=6 en-affil=School of Earth Sciences, Zhejiang University kn-affil= affil-num=7 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=8 en-affil=School of Earth Sciences, University of Bristol kn-affil= affil-num=9 en-affil=Earth & Planets Laboratory, Carnegie Institution for Science kn-affil= affil-num=10 en-affil=Universit? Clermont Auvergne, CNRS, IRD, OPGC, Laboratoire Magmas et Volcans kn-affil= affil-num=11 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=12 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=13 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=14 en-affil=Synchrotron SOLEIL kn-affil= affil-num=15 en-affil=Synchrotron SOLEIL kn-affil= affil-num=16 en-affil=Department of Earth Sciences, University College London kn-affil= END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=524 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250322 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-term outcomes of salvage high-dose-rate brachytherapy for localized recurrence of prostate cancer following definitive radiation therapy: a retrospective analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Salvage high-dose-rate brachytherapy (HDR-BT) is a potential treatment for localized recurrence of prostate cancer following definitive radiation therapy. This study aimed to evaluate the long-term safety and efficacy of HDR-BT alone, without androgen deprivation therapy (ADT), in this patient population.
Methods We conducted a retrospective analysis of patients with prostate cancer who developed pathologically confirmed local recurrence after definitive radiation therapy and were treated with salvage HDR-BT alone at Kawasaki Medical School Hospital between 2007 and 2021. The prescribed HDR-BT dose was 22 Gy in 2 fractions. Biochemical relapse-free survival (bRFS), cause-specific survival (CSS), and overall survival (OS) were assessed using the Kaplan?Meier method. Adverse events were evaluated based on the Common Terminology Criteria for Adverse Events.
Results Thirty-five patients were included, with a median follow-up of 66.0 months (range, 8.1?169.1). The 5-year bRFS, CSS, and OS rates were 29.7%, 100%, and 89.3%, respectively. Biochemical recurrence occurred in 21 patients (60.0%). Grade 2 adverse events were reported in eight patients (22.9%), while two (5.7%) experienced grade 3 adverse events. All grade 3 adverse events occurred in patients who had HDR-BT as their initial definitive radiation therapy.
Conclusions Salvage HDR-BT without ADT is a safe and effective treatment option for localized prostate cancer recurrence after definitive radiation therapy. It provides excellent CSS rates with acceptable toxicity while potentially reducing the need for ADT. Further prospective studies are warranted to confirm these findings. en-copyright= kn-copyright= en-aut-name=WatanabeKenta en-aut-sei=Watanabe en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KamitaniNobuhiko en-aut-sei=Kamitani en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkedaNaoki en-aut-sei=Ikeda en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawataYujiro en-aut-sei=Kawata en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TokiyaRyoji en-aut-sei=Tokiya en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HayashiTakafumi en-aut-sei=Hayashi en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyajiYoshiyuki en-aut-sei=Miyaji en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TamadaTsutomu en-aut-sei=Tamada en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatsuiKuniaki en-aut-sei=Katsui en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Urology, Kawasaki Medical School kn-affil= affil-num=8 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=9 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= en-keyword=Prostate cancer kn-keyword=Prostate cancer en-keyword=Radiation therapy kn-keyword=Radiation therapy en-keyword=High kn-keyword=High en-keyword=Dose kn-keyword=Dose en-keyword=Rate brachytherapy kn-keyword=Rate brachytherapy en-keyword=Salvage therapy kn-keyword=Salvage therapy en-keyword=Biochemical recurrence kn-keyword=Biochemical recurrence en-keyword=Local recurrence kn-keyword=Local recurrence en-keyword=Androgen deprivation therapy kn-keyword=Androgen deprivation therapy en-keyword=Long kn-keyword=Long en-keyword=Term outcomes kn-keyword=Term outcomes en-keyword=Toxicity kn-keyword=Toxicity en-keyword=Cause kn-keyword=Cause en-keyword=Specific survival kn-keyword=Specific survival END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=6 article-no= start-page=324 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250531 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Global Incidence Trend of Early-Onset Obesity-Related and Non-Obesity-Related Cancers en-subtitle= kn-subtitle= en-abstract= kn-abstract=The global rise in obesity prevalence and the incidence of early-onset cancer (diagnosed between 20 and 49 years of age) is a serious public health concern. We, therefore, evaluated the recent global trends in the incidence of early-onset obesity-related cancers and compared them to those of non-obesity-related cancers. We obtained age-standardized incidence rates of early-onset cancers diagnosed between 2000 and 2012 in 44 countries from the Cancer Incidence in Five Continents database. Using joinpoint regression models, we calculated the average annual percentage changes (AAPCs) and their corresponding 95% confidence intervals (95% CIs) for combined and individual categories of obesity-related cancers (11 and 9 cancer types in females and males, respectively) and non-obesity-related cancers (12 cancer types in both females and males). Differences in the AAPC were assessed by comparing 95% CIs, where nonoverlapping 95% CIs were considered statistically significantly different. We observed statistically significant positive AAPCs for early-onset obesity-related cancers in all available countries combined among females (global AAPC, 4.3%; 95% CI, 4.1?4.6%) and males (global AAPC, 1.4%; 95% CI, 1.2?1.7%). When analyzed by countries, we observed statistically significant positive AAPCs in 26 countries among females and 11 countries among males. AAPCs for early-onset obesity-related cancers were statistically significantly higher than those of non-obesity-related cancers in several regions, especially North America and Oceania. In conclusion, this study indicates that the incidence of early-onset obesity-related cancers exhibited a more pronounced increasing trend than non-obesity-related cancers among both sexes in many countries and regions. en-copyright= kn-copyright= en-aut-name=TerashimaMiyu en-aut-sei=Terashima en-aut-mei=Miyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakayamaKota en-aut-sei=Nakayama en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UgaiSatoko en-aut-sei=Ugai en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LeeHwa-Young en-aut-sei=Lee en-aut-mei=Hwa-Young kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsukumoYuta en-aut-sei=Tsukumo en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MizunoHiroki en-aut-sei=Mizuno en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SongMinkyo en-aut-sei=Song en-aut-mei=Minkyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SasamotoNaoko en-aut-sei=Sasamoto en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawachiIchiro en-aut-sei=Kawachi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UgaiTomotaka en-aut-sei=Ugai en-aut-mei=Tomotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Okayama University Medical School kn-affil= affil-num=2 en-affil=Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA kn-affil= affil-num=4 en-affil=Graduate School of Public Health and Healthcare Management, The Catholic University of Korea kn-affil= affil-num=5 en-affil=Department of Epidemiology, Harvard T.H. Chan School of Public Health kn-affil= affil-num=6 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Epidemiology, Harvard T.H. Chan School of Public Health kn-affil= affil-num=8 en-affil=Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health kn-affil= affil-num=9 en-affil=Public Health Sciences Division, Fred Hutchinson Cancer Center kn-affil= affil-num=10 en-affil=Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health kn-affil= affil-num=11 en-affil=Department of Epidemiology, Harvard T.H. Chan School of Public Health kn-affil= en-keyword=neoplasms kn-keyword=neoplasms en-keyword=etiology kn-keyword=etiology en-keyword=risk factors kn-keyword=risk factors en-keyword=global health kn-keyword=global health en-keyword=young adults kn-keyword=young adults END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=1 article-no= start-page=57 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Electrical conductivity measurements of rhyolitic glass at high pressure and high temperature en-subtitle= kn-subtitle= en-abstract= kn-abstract=We performed electrical conductivity measurements of rhyolite glasses across the glass transition temperature at 1 GPa. Our experimental data show that, in the Arrhenius plot, the conductivity of rhyolite with 0.2 wt% H2O has an inflection point between around 760 K, while for rhyolite with 4.9 wt% H2O the gradient changes between 685 and 825 K. These inflection points correlate with the glass transition temperature, and are compared with results of previous experiments. The degree of welding of clastic and hydrous rock can be constrained by estimating glass transition temperatures of volcanic rocks combined with measurements of electrical conductivity structures obtained from electromagnetic soundings beneath volcanic bodies. This, in turn, can be used to aid predictions of volcanic eruption. en-copyright= kn-copyright= en-aut-name=HaraguchiYusuke en-aut-sei=Haraguchi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Fuji-TaKiyoshi en-aut-sei=Fuji-Ta en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=NakamotoMasashi en-aut-sei=Nakamoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiMasanori en-aut-sei=Suzuki en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaToshihiro en-aut-sei=Tanaka en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Engineering, The University of Osaka kn-affil= affil-num=2 en-affil=Graduate School of Engineering, The University of Osaka kn-affil= affil-num=3 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Engineering, The University of Osaka kn-affil= affil-num=5 en-affil=Graduate School of Engineering, The University of Osaka kn-affil= affil-num=6 en-affil=Graduate School of Engineering, The University of Osaka kn-affil= en-keyword=Electrical conductivity kn-keyword=Electrical conductivity en-keyword=Glass transition temperature kn-keyword=Glass transition temperature en-keyword=melt kn-keyword=melt en-keyword=clastics kn-keyword=clastics END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=14404 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260217 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Boulder populations and orientation trends on asteroid Ryugu: implications for rubble-pile surface processes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Asteroid (162173) Ryugu is a spinning-top shaped, rubble-pile C-type asteroid with a surface dominated by boulders spanning a broad size-range. Using Hayabusa2 ONC-T mosaics for mapping, we present the most extensive global boulder dataset to date, representing an eleven-fold increase over the earliest survey and greater completeness than later AI-based estimates. Crucially, this work provides the first global boulder orientation dataset. The cumulative size-frequency distribution follows a power-law slope of ??2.665?}?0.066 (boulders???3 m), indicating its fragmented nature. Boulder density is lower along the equatorial ridge, consistent with regolith accumulation during earlier YORP-driven spin-up and poleward migration of blocks during the present spin-down phase. Orientation analyses reveal systematic hemispheric trends in what we define as slope-breaker zones (i.e., regions of high slope differentials), with NW?SE alignment in the northern hemisphere and NE?SW in the southern hemisphere, but absent at the equatorial ridge and poles. We interpret these as reorientations that developed during downslope boulder migration, as despite ongoing spin-down, the current spin rate remains high enough to drive such motion. In addition, fresh craters exhibit locally heightened boulder densities, recording ongoing resurfacing by impact events that exhume buried subsurface boulders and segregate them from finer regolith via seismic shaking induced granular convection. Together, these results yield new insights into rubble-pile surface evolution, rotational dynamics, and impact-driven resurfacing, with boulder orientations providing critical evidence of spin-related downslope transport and establish a framework for comparative asteroid studies. en-copyright= kn-copyright= en-aut-name=RayAditya en-aut-sei=Ray en-aut-mei=Aditya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RujTrishit en-aut-sei=Ruj en-aut-mei=Trishit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KomatsuGoro en-aut-sei=Komatsu en-aut-mei=Goro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=VincentLisa M. en-aut-sei=Vincent en-aut-mei=Lisa M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuchiHiroshi en-aut-sei=Kikuchi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HemmiRyodo en-aut-sei=Hemmi en-aut-mei=Ryodo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Orm?Jens en-aut-sei=Orm? en-aut-mei=Jens kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=International Research School of Planetary Sciences, Universit? G. deAnnunzio kn-affil= affil-num=4 en-affil=Department of Earth Sciences, Utrecht University kn-affil= affil-num=5 en-affil=Gakushuin University kn-affil= affil-num=6 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=7 en-affil=Centro de Astrobiolog?a (CAB), CSIC-INTA kn-affil= en-keyword=Asteroid Ryugu kn-keyword=Asteroid Ryugu en-keyword=Asteroidal surfaces kn-keyword=Asteroidal surfaces en-keyword=Regolith kn-keyword=Regolith en-keyword=Geological processes kn-keyword=Geological processes en-keyword=Impact processes kn-keyword=Impact processes END start-ver=1.4 cd-journal=joma no-vol=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 physiciansf 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 physiciansf 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 physiciansf 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=169 end-page=178 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Peripheral Blood T-Cell Receptor Repertoire and Host Immune Background in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=The association between peripheral blood T-cell receptor (TCR) repertoire and chemotherapy response remains unclear. We evaluated peripheral blood TCR repertoire and gut microbiota in 21 breast cancer patients receiving neoadjuvant chemotherapy (NAC) who were enrolled in the SBP-14 prospective cohort study between October 2019 and March 2022. We analyzed stool samples obtained pre-NAC and peripheral blood samples obtained pre- and post-NAC. The primary endpoint was the association between baseline peripheral blood TCR repertoire and treatment response. Eleven patients (52%) had hormone receptor-positive breast cancer. All patients received anthracyclines and taxanes, with anti-HER2 therapy for HER2-positive disease. TCR diversity (TCR alpha chain [TRA], p=0.095; TCR beta chain [TRB], p=0.051) and clonality (TRA, p=0.271; TRB, p=0.500) were not significantly associated with treatment response. Gut microbiota diversity was not correlated with TCR diversity (TRA: ƒÏ=0.046, p=0.845; TRB: ƒÏ=0.021, p=0.929); however, three bacterial orders (Erysipelotrichales, Bacillales, and Pasteurellales) were significantly associated with TCR repertoire. Baseline TCR repertoire was not associated with treatment response in this cohort of breast cancer patients. en-copyright= kn-copyright= en-aut-name=NakamuraYuki en-aut-sei=Nakamura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwamotoTakayuki en-aut-sei=Iwamoto en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KajiwaraYukiko en-aut-sei=Kajiwara en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HidaAkira en-aut-sei=Hida en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamotoShogo en-aut-sei=Nakamoto en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyoshiYuichiro en-aut-sei=Miyoshi en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IkedaMasahiko en-aut-sei=Ikeda en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OgataRyohei en-aut-sei=Ogata en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KoikeYoshikazu en-aut-sei=Koike en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NomuraTsunehisa en-aut-sei=Nomura en-aut-mei=Tsunehisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TanakaKatsuhiro en-aut-sei=Tanaka en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakashimaKazutaka en-aut-sei=Nakashima en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamatsujiTomoki en-aut-sei=Yamatsuji en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TairaNaruto en-aut-sei=Taira en-aut-mei=Naruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=2 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=3 en-affil=Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=4 en-affil=Department of Pathology, Matsuyama Shimin Hospital kn-affil= affil-num=5 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Breast Endocrine Surgery, Kagawa Prefectural Center Hospital kn-affil= affil-num=7 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Breast and Thyroid Surgery, Fukuyama City Hospital kn-affil= affil-num=9 en-affil=Department of General Surgery, Kawasaki Medical School General Medical Center kn-affil= affil-num=10 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=11 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=12 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=13 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=14 en-affil=Department of General Surgery, Kawasaki Medical School General Medical Center kn-affil= affil-num=15 en-affil=Department of General Surgery, Kawasaki Medical School General Medical Center kn-affil= affil-num=16 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital kn-affil= en-keyword=TCR repertoire kn-keyword=TCR repertoire en-keyword=gut microbiota kn-keyword=gut microbiota en-keyword=neoadjuvant chemotherapy kn-keyword=neoadjuvant chemotherapy en-keyword=breast cancer kn-keyword=breast cancer END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=3 article-no= start-page=159 end-page=168 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Self-Reported Adolescent Menstrual Symptoms and Delayed Gynecologic Consultation among Japanese Women with Endometriosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Endometriosis symptoms often first appear during adolescence, yet delays in seeking gynecologic consultation remain a persistent challenge worldwide. Despite growing international evidence, the specific patterns of symptom recognition and consultation delay among Japanese women ? particularly in relation to self-monitoring behaviors and cultural barriers ? remain poorly understood. This study aimed to provide foundational data to guide menstrual education and preconception care strategies by conducting a cross-sectional online survey with retrospective recall among women with endometriosis to assess menstrual characteristics and symptom patterns from adolescence to initial care seeking. The survey was conducted in Japan in January 2024 and enrolled 166 women with endometriosis and 200 controls. Participants reported current and adolescent menstrual characteristics, symptom recognition, analgesic and low-dose estrogen?progestin use, school/work impact, and age at first gynecologic consultation for menstrual problems. Women with endometriosis reported heavier bleeding, stronger pain, and greater school/work absence than controls, both currently and retrospectively. The median age at first recognition of heavy bleeding or school/work absence was 16 years, whereas consultation occurred at approximately 21-23 years, indicating a consultation delay of 5-6 years. Notably, while self-monitoring of symptoms was more frequent among women with endometriosis, it only modestly shortened consultation delays. This study provides evidence from Japan that consultation delay persists despite active self-monitoring of symptoms, highlighting the influence of educational and cultural barriers on health-seeking behavior. These findings underscore the importance of integrating menstrual education with clinical guidance to promote timely gynecologic consultation. en-copyright= kn-copyright= en-aut-name=IkedaTomoko en-aut-sei=Ikeda en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakatsukaMikiya en-aut-sei=Nakatsuka en-aut-mei=Mikiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Health Sciences, Okayama University kn-affil= en-keyword=endometriosis kn-keyword=endometriosis en-keyword=adolescence kn-keyword=adolescence en-keyword=menstrual disorders kn-keyword=menstrual disorders en-keyword=consultation delay kn-keyword=consultation delay en-keyword=health-seeking behavior kn-keyword=health-seeking behavior END start-ver=1.4 cd-journal=joma no-vol= 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? 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=15 cd-vols= no-issue=4 article-no= start-page=e0087625 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=Draft genome sequence of blaIMP-1-carrying Phytobacter ursingii OUH-01, isolated from the feces of an acute lymphoblastic leukemia patient en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report the 5.7 Mbp draft genome of carbapenem-resistant Phytobacter ursingii strain OUH-01, recovered from the feces of a patient with acute lymphoblastic leukemia. The genome comprises a chromosome (G+C content of 53.5%), three plasmids, and four linear contigs, including the 222 kb plasmid pOUH-phyto-IMP-01 carrying blaIMP-1. Nanopore/Illumina sequencing achieved 235~ coverage. en-copyright= kn-copyright= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UrakamiIori en-aut-sei=Urakami en-aut-mei=Iori 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= affil-num=1 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of 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 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= en-keyword=Enterobacteriaceae kn-keyword=Enterobacteriaceae en-keyword=carbapenems kn-keyword=carbapenems 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=17 cd-vols= no-issue=1 article-no= start-page=4963 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural insights into YheS-mediated release of SecM-arrested ribosome en-subtitle= kn-subtitle= en-abstract= kn-abstract=ATP-binding cassette subfamily F (ABCF) proteins interact with the ribosome to resolve translation defects near the peptidyl transferase center (PTC). In Escherichia coli, four ABCF proteins (EttA, Uup, YbiT, and YheS) selectively promote translation of distinct problematic nascent peptide sequences, but their molecular mechanisms remain unclear. Here, we present a 2.8?? cryo-EM structure of the ribosome in complex with an ATPase-deficient mutant of YheS and investigate how it releases ribosomes arrested by the SecM nascent chain. YheS binds to the ribosomal E-site via the L1 stalk, and its P-site tRNA-interaction motif (PtIM) extends toward the PTC, displacing the CCA end of the P-site tRNA. Notably, the cryo-EM density corresponding to the SecM nascent chain within the exit tunnel is largely lost upon YheS binding. These observations suggest that YheS relieves peptide sequence-dependent stalling by perturbing nascent chain-tunnel interactions through P-site tRNA relocation. Steered molecular dynamics simulations provide qualitative support for this model. Together, our findings provide mechanistic insight into a mode of arrest release distinct from the translocon-mediated release mechanism. en-copyright= kn-copyright= en-aut-name=IsoKaishi en-aut-sei=Iso en-aut-mei=Kaishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaToma en-aut-sei=Ikeda en-aut-mei=Toma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamasakiKohei en-aut-sei=Yamasaki en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AndoYushin en-aut-sei=Ando en-aut-mei=Yushin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SanoFumiya K. en-aut-sei=Sano en-aut-mei=Fumiya K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FurutaTadaomi en-aut-sei=Furuta en-aut-mei=Tadaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TaguchiHideki en-aut-sei=Taguchi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NurekiOsamu en-aut-sei=Nureki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ChadaniYuhei en-aut-sei=Chadani en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItohYuzuru en-aut-sei=Itoh en-aut-mei=Yuzuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=2 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=6 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=7 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=8 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=9 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=6 article-no= start-page=1053 end-page=1061 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260423 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Two-dimensional metal?organic frameworks offer all-in-one cocatalysts for photocatalytic overall water splitting en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photocatalytic overall water splitting holds great promise for sustainable hydrogen production. For overall water splitting performed by one-step excitation, both the hydrogen evolution and oxygen evolution reactions are hindered kinetically; hence, it is necessary to employ site-selective modification of photocatalysts with hydrogen-evolving and oxygen-evolving cocatalysts. However, critical challenges remain, including the need for cumbersome, multi-step photodeposition processes and durable blocking layers to inhibit the reverse reactions. Here we find a conductive, two-dimensional metal?organic framework to serve as a simple, multifunctional cocatalyst. We loaded this framework on SrTiO3:Al, an overall water-splitting photocatalyst, using a one-step self-assembly method. The framework cocatalyst promoted steady photocatalysis with an apparent quantum efficiency of 31.5% at 350?nm, free from the reverse reaction even without blocking layers. We proposed the operational principles for the cocatalyst activity using spectroscopic, electrochemical and theoretical analyses. This two-dimensional metal?organic framework offers an all-in-one approach for designing efficient and practical one-step excitation overall water-splitting systems. en-copyright= kn-copyright= en-aut-name=GuanJingyan en-aut-sei=Guan en-aut-mei=Jingyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiHajime en-aut-sei=Suzuki en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KamiyaKazuhide en-aut-sei=Kamiya en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaradaTakashi en-aut-sei=Harada en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AdachiRintaro en-aut-sei=Adachi en-aut-mei=Rintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TomitaOsamu en-aut-sei=Tomita en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurokawaHirofumi en-aut-sei=Kurokawa en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UnabaraDaisuke en-aut-sei=Unabara en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YonekuraKoji en-aut-sei=Yonekura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukuiNaoya en-aut-sei=Fukui en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaedaHiroaki en-aut-sei=Maeda en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SugimotoKunihisa en-aut-sei=Sugimoto en-aut-mei=Kunihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamaguchiYuichi en-aut-sei=Yamaguchi en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SaekiAkinori en-aut-sei=Saeki en-aut-mei=Akinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamakataAkira en-aut-sei=Yamakata en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KudoAkihiko en-aut-sei=Kudo en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AbeRyu en-aut-sei=Abe en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SakamotoRyota en-aut-sei=Sakamoto en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University kn-affil= affil-num=2 en-affil=Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University kn-affil= affil-num=3 en-affil=Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=4 en-affil=Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University kn-affil= affil-num=7 en-affil=Institute of Multidisciplinary Research for Advanced Materials, Tohoku University kn-affil= affil-num=8 en-affil=Institute of Multidisciplinary Research for Advanced Materials, Tohoku University kn-affil= affil-num=9 en-affil=Institute of Multidisciplinary Research for Advanced Materials, Tohoku University kn-affil= affil-num=10 en-affil=Research Institute for Science and Technology, Tokyo University of Science kn-affil= affil-num=11 en-affil=Research Institute for Science and Technology, Tokyo University of Science kn-affil= affil-num=12 en-affil=Department of Chemistry, Kindai University kn-affil= affil-num=13 en-affil=Department of Applied Chemistry, Faculty of Science, Tokyo University of Science kn-affil= affil-num=14 en-affil=Innovative Catalysis Science Division, Institute for Open and Transdisciplinary Research Initiatives, The University of Osaka kn-affil= affil-num=15 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=16 en-affil=Department of Applied Chemistry, Faculty of Science, Tokyo University of Science kn-affil= affil-num=17 en-affil=Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University kn-affil= affil-num=18 en-affil=Department of Chemistry, Graduate School of Science, Tohoku University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=1 end-page=17 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Afatinib Overcomes Osimertinib Resistance via Egfr V804F Mutation in a Syngeneic Egfr-Mutant Lung Cancer Mouse Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osimertinib is the standard first-line treatment for advanced EGFR-mutant non-small cell lung cancer. However, acquired resistance invariably develops, and identifying novel resistance pathways is clinically important as a substantial portion remains undefined. We used an immunocompetent syngeneic lung cancer mouse model harboring an Egfr exon 19 deletion (mDEL tumors) to establish acquired resistance. Osimertinib-resistant tumors were generated in vivo using a drug-holiday/re-challenge protocol. The resistance mechanism was identified using Sanger sequencing, receptor tyrosine kinase arrays, and western blotting. Egfr V804F knock-in cells were generated using CRISPR/Cas9, and their sensitivity to osimertinib and afatinib was assessed in vitro and in vivo. We established two distinct osimertinib-resistant tumor lines in a syngeneic lung cancer mouse model (mDEL OsiR #1/#3). The analysis revealed an on-target secondary Egfr V804F mutation (corresponding to human EGFR V802F) in both tumor lines. Importantly, Egfr V804F knock-in cells demonstrated significant osimertinib resistance, with a 5.7?10.5-fold increase in in vitro IC50 (mean, 8.2-fold), but remained highly sensitive to afatinib. Furthermore, afatinib effectively overcame osimertinib resistance in the V804F knock-in cell-derived mouse model. Consistently, afatinib treatment resulted in marked tumor shrinkage and suppression of EGFR signaling in the established mDEL OsiR #1/#3 in vivo. These findings establish secondary Egfr V804F/EGFR V802F as an on-target osimertinib resistance mechanism, providing a preclinical rationale for evaluating afatinib in biomarker-selected patients harboring this alteration. en-copyright= kn-copyright= en-aut-name=TanakaTakaaki en-aut-sei=Tanaka en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujitaniMasato en-aut-sei=Fujitani en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaokaMasataka en-aut-sei=Taoka en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShimomuraIwao en-aut-sei=Shimomura en-aut-mei=Iwao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkawaSachi en-aut-sei=Okawa en-aut-mei=Sachi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriShunta en-aut-sei=Mori en-aut-mei=Shunta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishimuraJun en-aut-sei=Nishimura en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishimuraTomoka en-aut-sei=Nishimura en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MoritaAyako en-aut-sei=Morita en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HaraNaofumi en-aut-sei=Hara en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KatayamaRyohei en-aut-sei=Katayama en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= affil-num=12 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= affil-num=14 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= affil-num=15 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= affil-num=16 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= affil-num=17 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=19 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= affil-num=20 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= affil-num=22 en-affil=Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research kn-affil= affil-num=23 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University kn-affil= en-keyword=afatinib kn-keyword=afatinib en-keyword=EGFR-mutant NSCLC kn-keyword=EGFR-mutant NSCLC en-keyword=exon 19 deletion kn-keyword=exon 19 deletion en-keyword=osimertinib resistance kn-keyword=osimertinib resistance en-keyword=V802F (human EGFR)/V804F (murine Egfr) kn-keyword=V802F (human EGFR)/V804F (murine Egfr) END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=2 article-no= start-page=e1012045 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260217 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Octopamine signaling from clock neurons plays dual roles in Drosophila long-term memory en-subtitle= kn-subtitle= en-abstract= kn-abstract=Circadian clock genes are best known for regulating circadian rhythms, but they also play crucial roles in memory processes. This suggests that memory is modulated by neural networks containing clock neurons, although the underlying mechanisms remain unclear. In Drosophila melanogaster, approximately 240 clock neurons are grouped into at least eight distinct clusters. Among them, the dorsal?lateral neurons (LNds) are required for maintaining long-term memory (LTM). In contrast, the neuropeptide Pigment-dispersing factor (Pdf), expressed in both small and large ventral?lateral neurons (s-LNvs and l-LNvs, respectively), functions as a circadian output signal and is also essential for maintaining LTM. In addition, Pdf-expressing neurons (hereafter, Pdf neurons) release neurotransmitters other than Pdf, which are involved in LTM consolidation. However, the specific transmitters used by LNds and Pdf neurons in LTM processing have remained unknown. Here, we show that octopamine signaling from LNds is essential for LTM maintenance, whereas octopamine in Pdf neurons is essential for LTM consolidation. Temporally restricted knockdown of Tyramine ƒÀ hydroxylase (Tbh), the gene encoding the enzyme required for octopamine synthesis, disrupted LTM maintenance when targeted in LNds, whereas it impaired LTM consolidation when targeted in Pdf neurons. Notably, Tbh knockdown in LNds or Pdf neurons had minimal effects on circadian behavioral rhythms or sleep. These findings reveal that octopamine released from specific subtypes of clock neurons independently regulates distinct phases of LTM in Drosophila. en-copyright= kn-copyright= en-aut-name=KurataYuto en-aut-sei=Kurata en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=SakaiTakaomi en-aut-sei=Sakai en-aut-mei=Takaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Biological Sciences, Tokyo Metropolitan 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=Department of Biological Sciences, Tokyo Metropolitan University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=11 article-no= start-page=4730 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260524 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genomic Basis of Lifestyle Divergence in Rice-Associated Burkholderia: From Pathogenesis to Plant Growth Promotion en-subtitle= kn-subtitle= en-abstract= kn-abstract=The genus Burkholderia encompasses both plant pathogenic and beneficial species, yet the genomic determinants underlying this lifestyle divergence remain poorly understood. Using 16S rRNA sequencing of 100 rice cultivars, our companion study demonstrated that resistant varieties are enriched in beneficial Burkholderiaceae, leading to the isolation of three phenotypically contrasting strains. Here, we present comparative genomic analyses of non-pathogenic biocontrol strain Burkholderia vietnamiensis J14EpLeaf2 and pathogenic strains Burkholderia gladioli A1EpSeed5 and Burkholderia cepacia J14Eple. Pathogenic strains possess significantly larger genomes (8.36?8.46 Mb) enriched in mobile genetic elements compared to the streamlined 6.95 Mb genome of B. vietnamiensis. CAZyme analysis revealed broader repertoires of glycoside hydrolases and polysaccharide lyases in pathogens, consistent with enhanced plant cell wall degradation. B. gladioli possesses a complete T3SS and expanded T6SS with 301 predicted effectors, while B. cepacia lacks structural T3SS genes but harbors 271 candidate effectors predicted to be secreted via alternative secretion pathways, compared to 180 in B. vietnamiensis. Notably, B. cepacia harbors cystic fibrosis-associated markers (cable pili, ZmpA/ZmpB), raising significant biosafety concerns that preclude its agricultural application. LC-MS validated IAA, ornibactin, and AHL production in B. vietnamiensis, supporting its plant growth-promoting and biocontrol functions. Computational PPI networks predicted distinct interaction landscapes requiring experimental validation. This study provides a genomic framework for distinguishing pathogenic from beneficial Burkholderia and supports B. vietnamiensis as a safe biocontrol agent while cautioning against B. cepacia J14Eple. en-copyright= kn-copyright= en-aut-name=OforiAndrews Danso en-aut-sei=Ofori en-aut-mei=Andrews Danso kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NasimiZohreh en-aut-sei=Nasimi en-aut-mei=Zohreh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AckahFrank Kwekucher en-aut-sei=Ackah en-aut-mei=Frank Kwekucher kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AhmedMuhammad Irfan en-aut-sei=Ahmed en-aut-mei=Muhammad Irfan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanYaoting en-aut-sei=Yan en-aut-mei=Yaoting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LiWang en-aut-sei=Li en-aut-mei=Wang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KandroAbdul Ghani en-aut-sei=Kandro en-aut-mei=Abdul Ghani kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkadaKazunori en-aut-sei=Okada en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 ORCID= en-aut-name=ZhengAiping en-aut-sei=Zheng en-aut-mei=Aiping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University kn-affil= affil-num=2 en-affil=State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University kn-affil= affil-num=3 en-affil=Department of Crop Science, School of Agriculture and Natural Sciences, University of Cape Coast kn-affil= affil-num=4 en-affil=State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University kn-affil= affil-num=5 en-affil=State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University kn-affil= affil-num=6 en-affil=State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University kn-affil= affil-num=7 en-affil=State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University kn-affil= affil-num=8 en-affil=Agro-Biotechnology Research Center, The University of Tokyo kn-affil= affil-num=9 en-affil=Bioproductivity Informatics Research Team, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=10 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=11 en-affil=State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University kn-affil= en-keyword=Burkholderia kn-keyword=Burkholderia en-keyword=comparative genomics kn-keyword=comparative genomics en-keyword=virulence factors kn-keyword=virulence factors en-keyword=secretion systems kn-keyword=secretion systems en-keyword=CAZymes kn-keyword=CAZymes en-keyword=plant-microbe interactions kn-keyword=plant-microbe interactions en-keyword=biocontrol kn-keyword=biocontrol en-keyword=pathogenicity kn-keyword=pathogenicity en-keyword=protein?protein interaction networks kn-keyword=protein?protein interaction networks en-keyword=rice sheath blight kn-keyword=rice sheath blight 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 ( 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=18 cd-vols= no-issue=7 article-no= start-page=1181 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260407 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Predictive Nomogram for Recurrence After Upfront Surgery for Resectable Pancreatic Ductal Adenocarcinoma: A Multicenter Study (OS-HBP-2) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Postoperative recurrence is a critical issue in the treatment of resectable pancreatic ductal adenocarcinoma (rPDAC). Moreover, the prognosis after early recurrence is extremely poor. This study aimed to develop a recurrence prediction model and to define early recurrence after upfront surgery (UFS) for rPDAC. Methods: This multicenter retrospective study included patients who underwent UFS for anatomically rPDAC between January 2013 and December 2017. Multivariate analyses were conducted to identify the risk factors for recurrence-free survival and to construct a recurrence prediction model. Subsequently, a minimum p value approach was used to determine the optimal cutoff values for early and late recurrence. Results: The cohort included 603 patients (325 men and 278 women). During the median follow-up period of 25 months (interquartile range, 15?38 months), 381 patients (63.2%) experienced a recurrence. Multivariate analyses revealed carbohydrate antigen 19-9 ?37 U/mL (hazard ratio [HR], 1.58; p < 0.001), tumor size ? 2.2 cm (HR, 1.59; p < 0.001), lymph node metastasis (HR, 1.86; p < 0.001), R1 resection (HR, 1.56; p = 0.002), and no adjuvant chemotherapy (HR, 1.54; p < 0.001) as independent predictors. The recurrence prediction model demonstrated an area under the curve of 0.72?0.75. The optimal threshold for early and late recurrences was a recurrence-free interval of five months. Carbohydrate antigen 19-9 ? 156 U/mL was a significant predictor of early recurrence (OR, 3.28; p < 0.001). Conclusions: This study identified the prognostic risk factors for recurrence and developed a recurrence prediction model for patients undergoing UFS for rPDAC. Moreover, a recurrence-free interval of five months was identified as the optimal threshold for distinguishing between early and late recurrences. en-copyright= kn-copyright= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiokiMasayoshi en-aut-sei=Hioki en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkabayashiTakehiro en-aut-sei=Okabayashi en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KojimaToru en-aut-sei=Kojima en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EndoYoshikatsu en-aut-sei=Endo en-aut-mei=Yoshikatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NobuokaDaisuke en-aut-sei=Nobuoka en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SuiKenta en-aut-sei=Sui en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=InagakiMasaru en-aut-sei=Inagaki en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShinouraSusumu en-aut-sei=Shinoura en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KimuraMasashi en-aut-sei=Kimura en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsudaTatsuo en-aut-sei=Matsuda en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AokiHideki en-aut-sei=Aoki en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Surgery, Fukuyama City Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Surgery, Okayama Saiseikai General Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Himeji Red Cross Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, Fukuyama City Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, Kagawa Prefectural Hospital kn-affil= affil-num=10 en-affil=Department of Surgery, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=11 en-affil=Department of Surgery, Tsuyama Chuo Hospital kn-affil= affil-num=12 en-affil=Department of Surgery, Matsuyama Shimin Hospital kn-affil= affil-num=13 en-affil=Department of Surgery, Tenwakai Matsuda Hospital kn-affil= affil-num=14 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=pancreatic cancer kn-keyword=pancreatic cancer en-keyword=resectable kn-keyword=resectable en-keyword=upfront surgery kn-keyword=upfront surgery en-keyword=recurrence kn-keyword=recurrence en-keyword=nomogram kn-keyword=nomogram END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=4 article-no= start-page=602 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Outcomes After Robot-Assisted Versus Open Pancreatoduodenectomy: A Propensity Score-Matching Analysis in a High-Volume Center (TAKUMI-7) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Although the safety and feasibility of robot-assisted pancreatoduodenectomy (RPD) compared to open pancreatoduodenectomy (OPD) have been reported, studies investigating the advantages of RPD remain limited. Moreover, only a few studies have investigated the effects of robotic surgery on textbook outcomes (TO). Methods: This single-center retrospective study included 400 patients who underwent RPD and OPD at our institution between January 2017 and December 2025. Outcomes were compared between the RPD (n = 162) and OPD (n = 238) groups using propensity score-matching (PSM) analysis. The factors associated with TO were examined. Results: Before PSM, significant differences were observed between the groups. PSM yielded RPD (n = 117) and OPD (n = 117) with equal preoperative factors. The RPD group demonstrated a significantly shorter operative time (402 vs. 444 min, p < 0.001), lesser blood loss (75 vs. 270 mL, p < 0.001), shorter postoperative hospital stays (13 vs. 22 days, p < 0.001), and fewer major complications (17.1 vs. 44.4%, p < 0.001), resulting in a higher TO achievement rate (76.9 vs. 52.1%, p = 0.001). Adjusted multivariate analyses identified robotic surgery (odds ratio 3.04, p < 0.001) as an independent predictor of TO. Conclusions: This study demonstrated that RPD was potentially superior to OPD in terms of short-term outcomes. Robotic surgery was significantly associated with TO after pancreatoduodenectomy at the expertfs hand. 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=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=YamadaMotohiko en-aut-sei=Yamada en-aut-mei=Motohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=9 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=10 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=11 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=12 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 Hepatobiliary Pancreatic Surgery, Ehime University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=pancreatoduodenectomy kn-keyword=pancreatoduodenectomy en-keyword=robotic surgery kn-keyword=robotic surgery en-keyword=open surgery kn-keyword=open surgery en-keyword=textbook outcome kn-keyword=textbook outcome 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=33 cd-vols= no-issue=7 article-no= start-page=6296 end-page=6305 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=Association of Preoperative Inspiratory Muscle Weakness and Respiratory Sarcopenia with Postoperative Pneumonia Following Esophagectomy: A Multicenter Retrospective Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Esophagectomy is associated with a high rate of postoperative pneumonia, which significantly impacts patient outcomes, including survival and quality of life. While some modifiable risk factors have been identified, the specific role of preoperative respiratory muscle function remains to be fully elucidated. Therefore, this study was designed to investigate the association of preoperative inspiratory muscle weakness (IMW) and respiratory sarcopenia (RS) with postoperative pneumonia in patients with esophageal cancer who underwent esophagectomy.
Methods Patients with esophageal cancer who underwent esophagectomy between July 2021 and June 2023 were enrolled in this multicenter, retrospective, cohort study. The primary outcome was postoperative pneumonia, while preoperative IMW and RS were the main exposures. Respiratory sarcopenia was defined as the presence of both IMW and low skeletal muscle mass, which is assessed by using bioelectrical impedance analysis. Associations were analyzed by using G-computation within a Bayesian framework.
Results A total of 213 patients were enrolled in this study. Postoperative pneumonia occurred in 42 patients (19.7%). Preoperative IMW was strongly associated with an increased risk of pneumonia, with a mean risk difference (RD) of 18.1% (95% credible interval [CrI] 5?33.6). The posterior probability that the RD exceeds 5% was >?98%. Respiratory sarcopenia also showed a potential association, although with greater uncertainty (mean RD, 11.2%; 95% CrI ??3.8 to 27.9). The posterior probability that the RD exceeds 5% was 76.7%.
Conclusions Preoperative IMW is a notable risk factor for postoperative pneumonia following esophagectomy. While a potential link with RS was found, its role remains uncertain and requires further investigation. en-copyright= kn-copyright= en-aut-name=OkuraKazuki en-aut-sei=Okura en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaTomohiro en-aut-sei=Ikeda en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoHiroki en-aut-sei=Sato en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatayamaSho en-aut-sei=Katayama en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiYusuke en-aut-sei=Takahashi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagakiYushi en-aut-sei=Nagaki en-aut-mei=Yushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WakitaAkiyuki en-aut-sei=Wakita en-aut-mei=Akiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= en-aut-name=FujiwaraYoshinori en-aut-sei=Fujiwara en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SatoYusuke en-aut-sei=Sato en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KasukawaYuji en-aut-sei=Kasukawa en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MiyakoshiNaohisa en-aut-sei=Miyakoshi en-aut-mei=Naohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Rehabilitation Medicine, Akita University Hospital kn-affil= affil-num=2 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Rehabilitation, Kawasaki University of Medical Welfare kn-affil= affil-num=4 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Rehabilitation Medicine, Akita University Hospital kn-affil= affil-num=6 en-affil=Department of Esophageal Surgery, Akita University Hospital kn-affil= affil-num=7 en-affil=Department of Esophageal Surgery, Akita University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Digestive Surgery, Kawasaki Medical School kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Esophageal Surgery, Akita University Hospital kn-affil= affil-num=13 en-affil=Department of Rehabilitation Medicine, Akita University Hospital kn-affil= affil-num=14 en-affil=Department of Rehabilitation Medicine, Akita University Hospital kn-affil= en-keyword=Inspiratory muscle kn-keyword=Inspiratory muscle en-keyword=Respiratory sarcopenia kn-keyword=Respiratory sarcopenia en-keyword=Postoperative pneumonia kn-keyword=Postoperative pneumonia en-keyword=Perioperative rehabilitation kn-keyword=Perioperative rehabilitation en-keyword=Esophagectomy kn-keyword=Esophagectomy en-keyword=Esophageal cancer kn-keyword=Esophageal cancer END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=1 end-page=13 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260514 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Atezolizumab + Chemotherapy in Older Patients With Lung Cancer in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pivotal phase 3 trials leading to the approvals of atezolizumab„Ÿchemotherapy combinations for non-small cell and extensive-stage small cell lung cancer (NSCLC and ES-SCLC) had strict eligibility criteria. J-TAIL-2 was a prospective, observational study in Japan that evaluated atezolizumab regimens for advanced NSCLC/ES-SCLC, including patients ineligible for global trials. The primary endpoint was 12-month overall survival (OS); safety and efficacy in subgroups defined by age, ECOG PS and/or G8 score, and creatinine clearance were key secondary endpoints. As of February 3, 2023, 1217 patients were treated in clinical practice based on Japanese labeling/treatment guidelines. Patients received atezolizumab with either carboplatin and nab-paclitaxel (atezo + CnP), carboplatin/cisplatin and pemetrexed (atezo + PP), or bevacizumab and carboplatin and paclitaxel (atezo + bev?+?CP) in the NSCLC cohort (n?=?814) or with carboplatin and etoposide (atezo + CE) in the ES-SCLC cohort (n?=?403). Overall, 53.5% were ??70?years old, and 11.8% had ECOG PS ??2; median G8 scores were 13 (NSCLC cohort) and 12 (ES-SCLC). Patients ?0.5 log2 fold change) and linked to clinical outcomes reported in J-TAIL-2. IL-6, MUC-16, and KRT-19 were associated with shorter progression-free survival across multiple regimens. Granzyme A and B, immune activation markers, were elevated in responders who received atezolizumab + CnP and atezolizumab + bev?+?CP. High levels of baseline immune stimulation proteins were associated with irAEs across regimens. Protein expression changes were varied and regimen-dependent in subgroup analyses including older patients and those with EGFR-mutant tumors. These data warrant further investigation across different cancer types and atezolizumab-containing regimens to determine their relevance to efficacy and irAE occurrence of atezolizumab combination therapy. en-copyright= kn-copyright= en-aut-name=GotoYasushi en-aut-sei=Goto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishioMakoto en-aut-sei=Nishio en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OsoegawaAtsushi en-aut-sei=Osoegawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuchiEiki en-aut-sei=Kikuchi en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KimuraHideharu en-aut-sei=Kimura en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimizuJunichi en-aut-sei=Shimizu en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyauchiEisaku en-aut-sei=Miyauchi en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshinoIchiro en-aut-sei=Yoshino en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MisumiToshihiro en-aut-sei=Misumi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WatanabeYasutaka en-aut-sei=Watanabe en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KatakamiNobuyuki en-aut-sei=Katakami en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KisoharaAkira en-aut-sei=Kisohara en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamaguchiMasafumi en-aut-sei=Yamaguchi en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KurokiHirotaka en-aut-sei=Kuroki en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SugimotoMasamichi en-aut-sei=Sugimoto en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=AshimuraHisao en-aut-sei=Ashimura en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TanakaMisa en-aut-sei=Tanaka en-aut-mei=Misa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=GemmaAkihiko en-aut-sei=Gemma en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Kanazawa University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Tohoku University Hospital kn-affil= affil-num=9 en-affil=Department of Thoracic Oncology, Kansai Medical University kn-affil= affil-num=10 en-affil=Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital kn-affil= affil-num=11 en-affil=Department of Data Science, National Cancer Center Hospital East kn-affil= affil-num=12 en-affil=Department of Thoracic Oncology, Saitama Cancer Center kn-affil= affil-num=13 en-affil=Department of Pulmonary Medicine and Medical Oncology Takarazuka City Hospital Takarazuka Japan kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Kasukabe Medical Center kn-affil= affil-num=15 en-affil=Department of Thoracic Oncology, NHO Kyushu Cancer Center kn-affil= affil-num=16 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=17 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=18 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=19 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=20 en-affil=Nippon Medical School kn-affil= en-keyword=atezolizumab kn-keyword=atezolizumab en-keyword=biomarker kn-keyword=biomarker en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=plasma protein kn-keyword=plasma protein en-keyword=small cell lung cancer kn-keyword=small cell lung cancer END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=4-5 article-no= start-page=e70061 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=Computer]Aided Sperm Analysis Protocol for Evaluating Sperm Motility in Japanese Medaka en-subtitle= kn-subtitle= en-abstract= kn-abstract=Changes in sperm motility can serve as an early indicator of reproductive effects caused by environmental chemicals or genetic perturbations. However, sperm motility is highly sensitive to external factors such as osmolarity, ionic composition, and the timing of measurement after activation, making it challenging to obtain consistent and reproducible measurements. Here, we present a standardized protocol for assessing sperm motility in Japanese medaka (Oryzias latipes) using a sperm motility analysis system (SMAS), an application for computer-aided sperm motility analysis (CASA). This protocol details the procedures for sperm collection, activation, and quantitative motility assessment, with particular focus on changes in the percentage of motile sperm post activation and the effects of sperm cryopreservation. We demonstrate time-dependent declines in sperm motility and velocity, and highlight the importance of early post-activation measurements to accurately capture peak motility. Notably, cryopreservation significantly accelerated the decline in sperm motility rate without affecting the initial proportion of motile sperm. To enable reliable comparisons among experimental groups, we recommend standardizing the initiation time after sperm activation by using CASA, and show that measurements should be initiated within 1?min after activation to obtain consistent and reliable data. This standardized SMAS-based protocol provides a robust and reproducible framework for sperm motility analysis in medaka and will be valuable not only for studies in reproductive biology, toxicology, and environmental risk assessment but also for applied research, such as breeding of aquacultural fishes. en-copyright= kn-copyright= en-aut-name=KuroyanagiMiwa en-aut-sei=Kuroyanagi en-aut-mei=Miwa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=OkamotoKeigo en-aut-sei=Okamoto en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatoAi en-aut-sei=Kato en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamazakiTouko en-aut-sei=Yamazaki en-aut-mei=Touko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KameiYasuhiro en-aut-sei=Kamei en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeEiji en-aut-sei=Watanabe en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NaruseKiyoshi en-aut-sei=Naruse en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OginoYukiko en-aut-sei=Ogino en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Advanced Aquaculture Science, Faculty of Marine Bioscience and Technology, Fukui Prefectural University kn-affil= affil-num=2 en-affil=Ushimado Marine Institute, Faculty of Science, Okayama University kn-affil= affil-num=3 en-affil=Laboratory of Aquatic Molecular Developmental Biology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University kn-affil= affil-num=4 en-affil=Interuniversity Bio-Backup Project Center, National Institute for Basic Biology (NIBB) kn-affil= affil-num=5 en-affil=Laboratory of Bioresources, National Institutes of Natural Sciences kn-affil= affil-num=6 en-affil=Optics and Bioimaging Facility, NIBB kn-affil= affil-num=7 en-affil=Basic Biology Program, Graduate University for Advanced Studies (SOKENDAI) kn-affil= affil-num=8 en-affil=Laboratory of Bioresources, National Institutes of Natural Sciences kn-affil= affil-num=9 en-affil=Laboratory of Aquatic Molecular Developmental Biology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University kn-affil= en-keyword=computer-aided sperm motility analysis (CASA) kn-keyword=computer-aided sperm motility analysis (CASA) en-keyword=medaka kn-keyword=medaka en-keyword=sperm motility kn-keyword=sperm motility en-keyword=sperm motility analysis system (SMAS) kn-keyword=sperm motility analysis system (SMAS) 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 (ƒÏ = ?0.125, p < 0.05) and TSH (ƒÏ = ?0.202, p < 0.01) and positive correlations with albumin (ƒÏ = 0.227, p < 0.01) and FT4 (ƒÏ = 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= 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? Conclusions In HM following TLE, chorioretinal spikes and preoperative BCVA are significantly associated with the 3-month BCVA. In HM, a thin subfoveal choroid ( Methods: We conducted a retrospective multicenter study on 46 patients with advanced or metastatic sRCC receiving first-line ICI-based combination therapy between January 2018 and December 2024 (IO-IO: n =?18; IO-TKI: n =?28). In a comparative survival analysis, three favorable-risk patients in the IO-TKI group were excluded to align risk profiles, focusing on intermediate/poor-risk groups (n =?43). The primary endpoint was overall survival (OS).
Results: In the entire cohort (n =?46), the objective response rate was numerically higher in the IO-TKI group (64.3%) than in the IO-IO group (50.0%) (p =?0.37). In the comparative analysis of intermediate/poor-risk patients (n =?43), progression-free survival (PFS) was slightly longer (p =?0.071), and OS was significantly longer (p =?0.016) in the IO-TKI group than in the IO-IO group. A multivariable analysis adjusted for IMDC risk categories showed favorable survival with the IO-TKI regimen (HR 0.37, p =?0.061).
Conclusions: The present study indicates that first-line IO-TKI combination therapy represents a promising treatment option with a potential survival advantage over IO-IO therapy for Japanese patients with sRCC. However, due to the retrospective design and small sample size, reliably determining the comparative efficacy of these regimens remains challenging, and further validation is warranted. en-copyright= kn-copyright= en-aut-name=TamuraKeita en-aut-sei=Tamura en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsushitaYuto en-aut-sei=Matsushita en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeHiromitsu en-aut-sei=Watanabe en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorinakaHirofumi en-aut-sei=Morinaka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ToyodaShingo en-aut-sei=Toyoda en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NukayaTakuhisa en-aut-sei=Nukaya en-aut-mei=Takuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MaenosonoRyoichi en-aut-sei=Maenosono en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KomuraKazumasa en-aut-sei=Komura en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujitaKazutoshi en-aut-sei=Fujita en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakaharaKiyoshi en-aut-sei=Takahara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AzumaHaruhito en-aut-sei=Azuma en-aut-mei=Haruhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=InamotoTeruo en-aut-sei=Inamoto en-aut-mei=Teruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Urology, Hamamatsu University School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, Hamamatsu University School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Hamamatsu University School of Medicine kn-affil= affil-num=4 en-affil=Department of Urology, Jikei University School of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, Jikei University School of Medicine kn-affil= affil-num=6 en-affil=Department of Urology, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=9 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= affil-num=10 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=11 en-affil=Department of Urology, Kawasaki Medical School kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= affil-num=15 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=16 en-affil=Department of Urology, Hamamatsu University School of Medicine kn-affil= en-keyword=dual immunotherapy kn-keyword=dual immunotherapy en-keyword=immune checkpoint inhibitor kn-keyword=immune checkpoint inhibitor en-keyword=immunotherapy plus tyrosine kinase inhibitor kn-keyword=immunotherapy plus tyrosine kinase inhibitor en-keyword=sarcomatoid renal cell carcinoma kn-keyword=sarcomatoid renal cell carcinoma END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=1 end-page=9 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260426 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=What Is the Pterygomandibular Raphe? A Confluence of Fasciae Rather Than a Discrete Structure en-subtitle= kn-subtitle= en-abstract= kn-abstract=The pterygomandibular raphe (PMR) has traditionally been described as a fibrous or tendinous band connecting the bucinator (BM) and superior pharyngeal constrictor (SPCM) muscles. However, recent evidence has questioned its existence. This study aimed to reevaluate the anatomy of the pterygomandibular region by preserving fascial continuity and examining the relationships among adjacent muscles and connective tissues. Twenty-five sides from formalin-fixed cadaveric heads were examined. Twenty sides underwent macroscopic dissection under a surgical microscope, and five sides were sectioned axially and analyzed histologically using Masson's trichrome staining to assess muscle?fascia continuity. The buccopharyngeal fascia (BpF) adhered tightly to the posterolateral surface of the BM. A ligament-like bundle observed between the BM and medial pterygoid muscle corresponded to an artificial continuation of the BpF created by dissection. Axial sections revealed that the BpF, masseteric, and temporalis fasciae converged anteriorly on the lateral surface of the BM, while posteriorly, the BpF and temporalis fascia also merged, forming a confluence of fasciae. No discrete tendinous or ligamentous PMR was identified. The so-called PMR represents a dissection artifact rather than a true anatomical structure. These findings emphasize the importance of preserving fascial relationships and using precise terminology in anatomical and clinical contexts. en-copyright= kn-copyright= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamaShion en-aut-sei=Hama en-aut-mei=Shion kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukinoKeiko en-aut-sei=Fukino en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KikutaShogo en-aut-sei=Kikuta en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HurMi]Sun en-aut-sei=Hur en-aut-mei=Mi]Sun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=CespedesMaria Cristina Manzanares en-aut-sei=Cespedes en-aut-mei=Maria Cristina Manzanares kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhyamaYoshio en-aut-sei=Ohyama en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=KomuneNoritaka en-aut-sei=Komune en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KamochiHideaki en-aut-sei=Kamochi en-aut-mei=Hideaki 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= affil-num=1 en-affil=Department of Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine kn-affil= affil-num=2 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=3 en-affil=Department of Oral and Maxillofacial Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University kn-affil= affil-num=4 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=5 en-affil=Department of Anatomy, Daegu Catholic University School of Medicine kn-affil= affil-num=6 en-affil=Human Anatomy and Embryology Unit. Experimental Pathology and Therapeutics Department, Faculty of Medicine and Health Sciences, University of Barcelona kn-affil= affil-num=7 en-affil=Oral and Maxillofacial Surgery, Shizuoka City Shizuoka Hospital kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=10 en-affil=Department of Maxillofacial Surgery, Institute of Science Tokyo kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=anatomy kn-keyword=anatomy en-keyword=bucinator kn-keyword=bucinator en-keyword=connective tissue kn-keyword=connective tissue en-keyword=dentistry kn-keyword=dentistry en-keyword=fascia kn-keyword=fascia en-keyword=masticatory muscles kn-keyword=masticatory muscles en-keyword=oral surgery kn-keyword=oral surgery en-keyword=pharynx kn-keyword=pharynx END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=5671446 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Arthroscopically Confirmed Complete Healing of Anterior Cruciate Ligament Avulsion Fracture Following Four]Corner Pullout Repair Using Ultrahigh]Molecular]Weight Polyethylene Tapes: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a case of tibial insertion avulsion fracture of the anterior cruciate ligament (ACL). A 10-year-old boy who fell from a skateboard was diagnosed with a tibial insertion avulsion fracture of the ACL and was treated arthroscopically. The avulsed fragment was provisionally fixed with guide pins inserted into its four corners, and the lateral view was checked to avoid penetration of the growth plate. Two ultrahigh-molecular-weight polyethylene tapes were passed through the ACL just above its tibial insertion, pulled through the four-corner bone tunnels in an X-shaped configuration, and tightened. The patient was immobilized for 3 weeks, and partial weight bearing was initiated at 4 weeks. Bone union was confirmed at 6 months using plain radiographs, and second-look arthroscopy and implant removal were performed 8 months postoperatively. During arthroscopy, complete union with smooth continuity of the articular cartilage at the fracture site and a stable ACL were observed. The patient had a full knee range of motion and no pain at the final follow-up. en-copyright= kn-copyright= en-aut-name=KoharaToshiki en-aut-sei=Kohara en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkazakiYuki en-aut-sei=Okazaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyazawaShinichi en-aut-sei=Miyazawa en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FurumatsuTakayuki en-aut-sei=Furumatsu en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YokoyamaYusuke en-aut-sei=Yokoyama en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TamuraMasanori en-aut-sei=Tamura en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawadaKoki en-aut-sei=Kawada en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HasegawaTsubasa en-aut-sei=Hasegawa en-aut-mei=Tsubasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TetsunagaTomonori en-aut-sei=Tetsunaga en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaKazuki en-aut-sei=Yamada en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery , NHO Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery , Japanese Red Cross Okayama Hospital kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=3 article-no= start-page=491 end-page=498 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260317 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful management and 10-year survival of a rectal neuroendocrine tumor with rare systemic metastases via a non-portal venous pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metastatic neuroendocrine tumors (NETs) typically involve the liver and lymph nodes. Metastases in the orbit, heart, and ovary are rare and present unique clinical challenges. We report a woman who was 70 years old at the time of initial presentation with liver metastases from a rectal neuroendocrine tumor. Following a right hepatectomy for liver metastases, she remained free of hepatic recurrence for 10 years. Notably, four years after the right hepatectomy, she developed new metastases in the left orbit, right ventricle, and left ovary, with diplopia as the sole clinical symptom. This clinical course suggests a distinct metastatic pathway associated with the lower rectum that bypasses the portal circulation, consistent with the dual drainage system of the rectal region. Management involved a strategic multimodal approach that includes systemic therapy with everolimus and lanreotide as well as targeted surgical resectioning of the cardiac and ovarian lesions. The orbital lesion achieved a complete response through systemic therapy alone, preserving visual function. Currently, 10 years after the initial treatment, the patient maintains an excellent performance status (ECOG PS 0) while receiving peptide receptor radionuclide therapy (PRRT). This case demonstrates that recognizing atypical metastatic pathways and employing strategic multimodal therapies can achieve long-term survival and functional preservation in rectal NETs. en-copyright= kn-copyright= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TerasawaHiroyuki en-aut-sei=Terasawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KuiseTakashi en-aut-sei=Kuise en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama Red Cross Hospital kn-affil= affil-num=9 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=Rectal neuroendocrine tumor kn-keyword=Rectal neuroendocrine tumor en-keyword=Rare metastases kn-keyword=Rare metastases en-keyword=Multimodal treatment kn-keyword=Multimodal treatment END start-ver=1.4 cd-journal=joma no-vol=2026 cd-vols= no-issue=1 article-no= start-page=8863202 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Selective ARID1A Loss Restricted to the Undifferentiated Component of a Mismatch Repair]Deficient Gastric Carcinoma: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mismatch repair-deficient (dMMR) gastric carcinomas often harbor ARID1A alteration, but a sharply demarcated undifferentiated/rhabdoid component with selective ARID1A loss is uncommon and may create a diagnostic dilemma. An 80-year-old man underwent esophagogastroduodenoscopy for anemia, which revealed a circumferential Borrmann Type 3 lesion in the gastric body, and distal gastrectomy was performed. Histologically, the tumor was composed predominantly of undifferentiated carcinoma with focal rhabdoid features and a minute well-differentiated adenocarcinoma component, with an abrupt transition between the two. Immunohistochemistry showed loss of nuclear MLH1 and PMS2 in both components, whereas loss of ARID1A expression was confined to the undifferentiated component; SMARCB1 (INI1), SMARCA2 (BRM), and SMARCA4 (BRG1) were retained. EBER in situ hybridization was negative. Because gene-level testing, MSI testing, and MLH1 promoter methylation analysis were not performed, the molecular basis of the dMMR phenotype and ARID1A loss could not be determined. The restricted scope of molecular testing limits the ability to draw broad or generalizable conclusions and to fully establish clinicopathological correlations. The value of this report is, therefore, not mechanistic proof but recognition of a practical morphologic-immunophenotypic observation: When a gastric carcinoma shows a sharply demarcated shift from differentiated to undifferentiated/rhabdoid morphology, dMMR should be considered, and selective ARID1A loss in the undifferentiated component may be associated with dedifferentiation. These findings should be interpreted with caution as preliminary, hypothesis-generating observations that require validation in larger studies with more extensive molecular profiling. en-copyright= kn-copyright= en-aut-name=OmoteRika en-aut-sei=Omote en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamanoRyosuke en-aut-sei=Hamano en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaShinya en-aut-sei=Otsuka en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Diagnostic Pathology, NHO Fukuyama Medical Center kn-affil= affil-num=2 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=3 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pathology, Okayama University Hospital kn-affil= en-keyword=ARID1A kn-keyword=ARID1A en-keyword=carcinoma kn-keyword=carcinoma en-keyword=DNA mismatch repair deficiency kn-keyword=DNA mismatch repair deficiency en-keyword=rhabdoid features kn-keyword=rhabdoid features en-keyword=stomach neoplasms kn-keyword=stomach neoplasms en-keyword=SWI/SNF complex kn-keyword=SWI/SNF complex en-keyword=undifferentiated kn-keyword=undifferentiated END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=4 article-no= start-page=829 end-page=838 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Differences in drug efficacy and prognosis between primary and metastatic sites for de novo stage IV breast cancer: an exploratory analysis of a phase III trial, JCOG1017 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Breast cancer is a highly heterogeneous disease, with biological factors like estrogen receptor, progesterone receptor, and HER2 receptor differing between primary and metastatic sites, potentially affecting treatment response.
This exploratory analysis aims to differentiate drug efficacy and long-term prognosis between these sites in stage IV breast cancer.
Methods Patients from JCOG1017, a phase III trial evaluating the role of primary tumor resection, who received primary systemic therapy (PST) were evaluated at three months. In this analysis, treatment response was assessed separately in primary and metastatic sites. Patients were categorized into four groups: discordant I (primary non-PD, metastatic PD), concordant I (both PD), discordant II (primary PD, metastatic non-PD), and concordant II (both non-PD).
Results Among 271 patients, overall discordance proportion of treatment response between primary and metastatic sites was 25.1%. Group distribution was 24.7% (discordant I), 9.6% (concordant I), 0.4% (discordant II), and 65.3% (concordant II). Discordance was more frequent in luminal (28.9%), triple-negative (25.0%), and luminal-HER2 (22.0%) subtypes than in HER2-enriched (11.1%). Survival analysis showed prognostic differences: concordant II, with both sites non-PD, demonstrated the most favorable outcome compared with discordant I (HR 0.556; 95% confidence interval, 0.396?0.782).
Conclusions One-fourth of patients exhibited discordant responses between primary and metastatic sites in early treatment phases. These discrepancies were associated with survival differences, emphasizing the importance of evaluating both primary and metastatic lesions when assessing efficacy and determining treatment strategies in de novo stage IV breast cancer. en-copyright= kn-copyright= en-aut-name=TanakaKiyo en-aut-sei=Tanaka en-aut-mei=Kiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimomuraAkihiko en-aut-sei=Shimomura en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshitobiMakoto en-aut-sei=Ishitobi en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamanakaTakashi en-aut-sei=Yamanaka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsukiokiTakahiro en-aut-sei=Tsukioki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwataHiroji en-aut-sei=Iwata en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujisawaTomomi en-aut-sei=Fujisawa en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SasakiKeita en-aut-sei=Sasaki en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SadachiRyo en-aut-sei=Sadachi en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KajikawaRiku en-aut-sei=Kajikawa en-aut-mei=Riku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SakaiTakehiko en-aut-sei=Sakai en-aut-mei=Takehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SagaraYasuaki en-aut-sei=Sagara en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShigematsuHideo en-aut-sei=Shigematsu en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OzakiYukinori en-aut-sei=Ozaki en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NozawaKazuki en-aut-sei=Nozawa en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SudoKazuki en-aut-sei=Sudo en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NaitoYoichi en-aut-sei=Naito en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TerataKaori en-aut-sei=Terata en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IshibaToshiyuki en-aut-sei=Ishiba en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=FukudaHaruhiko en-aut-sei=Fukuda en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Breast Surgery, Toranomon Hospital kn-affil= affil-num=2 en-affil=Department of Breast and Medical Oncology, National Center for Global Health and Medicine kn-affil= affil-num=3 en-affil=Department of Breast Surgery, Osaka Habikino Medical Center kn-affil= affil-num=4 en-affil=Department of Breast Surgery, Kanagawa Cancer Center kn-affil= affil-num=5 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=7 en-affil=Department of Breast Oncology, Aichi Cancer Center kn-affil= affil-num=8 en-affil=Department of Breast Oncology, Gunma Prefectural Cancer Center kn-affil= affil-num=9 en-affil=Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=10 en-affil=Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=11 en-affil=Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=12 en-affil=Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=13 en-affil=Department of Breast Surgery, Sagara Hospital kn-affil= affil-num=14 en-affil=Department of Breast Surgery, Hiroshima University Hospital kn-affil= affil-num=15 en-affil=Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=16 en-affil=Department of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=17 en-affil=Department of Medical Oncology, National Cancer Center Hospital kn-affil= affil-num=18 en-affil=Department of General Internal Medicine, National Cancer Center Hospital East kn-affil= affil-num=19 en-affil=Department of Breast and Endocrine Surgery, Akita University Hospital kn-affil= affil-num=20 en-affil=Department of Breast Surgery, Institute of Science Tokyo Hospital kn-affil= affil-num=21 en-affil=Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=22 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=Discordance of treatment response between primary and metastatic sites kn-keyword=Discordance of treatment response between primary and metastatic sites en-keyword=De novo stage IV breast cancer kn-keyword=De novo stage IV breast cancer en-keyword=Primary systemic therapy kn-keyword=Primary systemic therapy en-keyword=Overall survival kn-keyword=Overall survival END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=3 article-no= start-page=528 end-page=536 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical complete response and predictive factors in HER2-positive early breast cancer treated with neoadjuvant chemotherapy aimed at omission of surgery: an exploratory analysis of the JCOG1806 trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose The JCOG1806 trial (jRCTs031190129) is underway to evaluate the omission of surgery in patients with human epidermal growth factor receptor (HER2)-positive early breast cancer who have a clinical complete response (cCR) after primary systemic therapy (PST). We aimed to assess the cCR rate in this trial and identify predictive factors.
Methods HER2-positivity was defined as an immunohistochemistry (IHC) score of 3?+?or in situ hybridization-positivity. A cCR was defined as the absence of detectable lesions upon palpation, contrast-enhanced magnetic resonance imaging, and ultrasonography; biopsy-based confirmation was optional in hormone receptor (HR)-negative cases and mandatory in HR-positive cases. Multivariate logistic regression analyses were used to identify predictors of a cCR.
Results The cCR rate was 57.6% (196/340 patients; 95% confidence interval [CI]: 52.2?63.0%). Strongly estrogen-receptor (ER)-positive tumors (??10%) were significantly less likely to have a cCR than ER-negative tumors (odds ratio [OR], 0.41; 95% CI: 0.20?0.81). IHC 3?+?tumors had higher cCR rates than IHC 1?+?or 2?+?tumors (OR, 2.19; 95% CI: 1.01?4.74). Compared with histological grade I tumors, cCR odds were higher in grade II (OR: 2.92; 95% CI: 1.07?7.93) and III (OR: 4.90; 95% CI: 1.76?13.7) tumors. Among patients without a cCR patients undergoing surgery, 22.2% were diagnosed with ypT0 tumors upon analysis of surgical specimens.
Conclusion ER-negativity, an IHC score of 3?+?, and a higher histological grade were independent predictors of a cCR. Identifying these features may improve the feasibility and safety of surgery omission for patients with HER2-positive early breast cancer. en-copyright= kn-copyright= en-aut-name=ShigematsuHideo en-aut-sei=Shigematsu en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujisawaTomomi en-aut-sei=Fujisawa en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwataHiroji en-aut-sei=Iwata en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshibaToshiyuki en-aut-sei=Ishiba en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OzakiYukinori en-aut-sei=Ozaki en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakaiTakehiko en-aut-sei=Sakai en-aut-mei=Takehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SagaraYasuaki en-aut-sei=Sagara en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimomuraAkihiko en-aut-sei=Shimomura en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SudoKazuki en-aut-sei=Sudo en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TerataKaori en-aut-sei=Terata en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NaitoYoichi en-aut-sei=Naito en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NozawaKazuki en-aut-sei=Nozawa en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SasakiKeita en-aut-sei=Sasaki en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MitomeNoriko en-aut-sei=Mitome en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SadachiRyo en-aut-sei=Sadachi en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ShibataTaro en-aut-sei=Shibata en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University Hospital kn-affil= affil-num=2 en-affil=Gunma Prefectural Cancer Center kn-affil= affil-num=3 en-affil=Aichi Cancer Center kn-affil= affil-num=4 en-affil=Graduate School of Medical Sciences, Nagoya City University kn-affil= affil-num=5 en-affil=Institute of Science Tokyo Hospital kn-affil= affil-num=6 en-affil=Cancer Institute Hospital of the Japanese Foundation for Cancer Research kn-affil= affil-num=7 en-affil=Cancer Institute Hospital of the Japanese Foundation for Cancer Research kn-affil= affil-num=8 en-affil=Hakuaikai Sagara Hospital kn-affil= affil-num=9 en-affil=National Center for Global Health and Medicine kn-affil= affil-num=10 en-affil=National Cancer Center Hospital kn-affil= affil-num=11 en-affil=Akita University Hospital kn-affil= affil-num=12 en-affil=National Cancer Center Hospital East kn-affil= affil-num=13 en-affil=Graduate School of Medical Sciences, Nagoya City University kn-affil= affil-num=14 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=15 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=16 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=17 en-affil=Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=18 en-affil=Okayama University Hospital kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Primary systemic therapy kn-keyword=Primary systemic therapy en-keyword=HER2 kn-keyword=HER2 en-keyword=cCR kn-keyword=cCR en-keyword=Omission of surgery kn-keyword=Omission of surgery END start-ver=1.4 cd-journal=joma no-vol=208 cd-vols= no-issue=6 article-no= start-page=2124 end-page=2133 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260415 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Decreased renal function predicts severe cytokine release syndrome after CAR-T-cell therapy for large B-cell lymphoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cytokine release syndrome (CRS) remains a major toxicity of chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL), and robust pre-infusion predictors are needed for risk-adapted management. We retrospectively analysed LBCL patients in the Japanese nationwide registry who underwent CD19 CAR-T-cell therapy between 2019 and 2024. Among 900 patients (median age 62?years), cumulative incidences of CRS within 30?days after infusion were 75.0% for any grade, 20.8% for grade???2 and 14.0% for grade???3. In multivariable analysis, lower estimated glomerular filtration rate (eGFR) (adjusted hazard ratio [aHR] 1.108 per 10?mL/min per 1.73?m2 decrease; 95% confidence interval [CI] 1.015?1.209; p?=?0.022), higher ferritin (aHR 1.006 per 100?ng/mL; 95% CI 1.001?1.010; p?=?0.016), C-reactive protein (CRP) (aHR 1.142 per mg/dL; 95% CI 1.091?1.195; p? Methods Two questionnaire surveys were conducted to investigate potential needs and barriers regarding online genetic care: one involving 858 medical professionals (738 physicians and 120 genetic counselors or nurses), and the other involving 443 clients who received in-person genetic counseling.
Results Only 14.0% of the medical professionals had experience with online genetic care, although 85.9% of the professionals engaged in cancer genetics were willing to consider providing it in the future. Notably, a discrepancy was found regarding hospital selection: clients prioritized access to specialized medical care, whereas professionals assumed clients valued accessibility for family members. Professionals expressed greater concerns about adequacy of online communication, client environments and internet security. Among clients, 89.1% estimated they would sufficiently understand and accept total content of counseling session if were conducted online. Older age and infrequent internet use were associated with lower acceptance and higher anxiety regarding online methods. Concerns about ability to use the necessary technology affected clientsf willingness to encourage online care for their relatives.
Conclusion Online genetic care shows high potential for client acceptance and can effectively address regional disparities in Japan. To bridge the gap between client needs and professional perceptions and to overcome the digital divide, it is necessary to develop secure, accessible systems and provide education for both patients and healthcare providers. en-copyright= kn-copyright= en-aut-name=UenoSayaka en-aut-sei=Ueno en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UrakawaYusaku en-aut-sei=Urakawa en-aut-mei=Yusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatoFumino en-aut-sei=Kato en-aut-mei=Fumino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UekiArisa en-aut-sei=Ueki en-aut-mei=Arisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanekoKeika en-aut-sei=Kaneko en-aut-mei=Keika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoKoji en-aut-sei=Matsumoto en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugawaraHiromi en-aut-sei=Sugawara en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiSayoko en-aut-sei=Takeuchi en-aut-mei=Sayoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshidaReiko en-aut-sei=Yoshida en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KakutaMiho en-aut-sei=Kakuta en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AkagiKiwamu en-aut-sei=Akagi en-aut-mei=Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TamuraKazuo en-aut-sei=Tamura en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= affil-num=1 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil= kn-affil= affil-num=4 en-affil=Division of Clinical Genetic Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research kn-affil= affil-num=5 en-affil=Division of Clinical Genetic Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research kn-affil= affil-num=6 en-affil=Division of Clinical Genetics, Hyogo Cancer Center kn-affil= affil-num=7 en-affil=Division of Clinical Genetics, Hyogo Cancer Center kn-affil= affil-num=8 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Medical Genetics and Genomics, Saitama Cancer Center kn-affil= affil-num=10 en-affil=Center for Genomic Diagnosis, International University of Health and Welfare (IUHW) Narita Hospital kn-affil= affil-num=11 en-affil=Center for Genomic Diagnosis, International University of Health and Welfare (IUHW) Narita Hospital kn-affil= affil-num=12 en-affil=Center for Genomic Diagnosis, International University of Health and Welfare (IUHW) Narita Hospital kn-affil= affil-num=13 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Hereditary cancer kn-keyword=Hereditary cancer en-keyword=Remote medical care kn-keyword=Remote medical care en-keyword=Barriers to online genetic care kn-keyword=Barriers to online genetic care en-keyword=Facilitators for online genetic care kn-keyword=Facilitators for online genetic care 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= cd-vols= no-issue= article-no= start-page= 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=A novel robot for CT-guided bone needle insertion with a rotational drilling and force-feedback speed control mechanism: preliminary evaluation in swine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose To evaluate the feasibility and accuracy of computed tomography (CT)-guided needle insertion into swine bones by using a novel robotic system capable of rotational drilling.
Materials and methods This was an animal experiment using three swine. A remote-controlled robot equipped with a rotational drilling and force-feedback insertion speed control mechanism was developed for bone needle insertion. Using the robot, CT-guided insertion of a 10-gauge bone access needle was attempted in the lumbar vertebrae, ilia, and femora six times each. Needle insertion accuracy was evaluated using the angle error, which is defined as the difference between the predetermined and post-insertion needle angles on axial and sagittal CT images. The time required for needle insertion was measured. The angle error and time required for needle insertion were compared among the bones using the Kruskal?Wallis test. Adverse events were also evaluated.
Results Robotic bone needle insertion was successful in all attempts. The median axial and sagittal angle errors were 0.21 and 0.21‹ for the lumbar vertebrae, 0.32 and 0.13‹ for the ilia, and 0.65 and 0.25‹ for the femora, respectively. Axial angle errors were significantly different among the bone types (p?=?0.038). The time required for needle insertion was 23.6, 21.3, and 59.7 s for the lumbar vertebrae, ilia, and femora, respectively. Time was significantly different among bone types (p?=?0.017). No adverse events were observed.
Conclusion CT-guided bone needle insertion using a robot equipped with a rotational drilling and force-feedback insertion speed control mechanism was feasible and accurate in swine. en-copyright= kn-copyright= en-aut-name=MatsuiYusuke en-aut-sei=Matsui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KimuraYuta en-aut-sei=Kimura en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasakiTakanori en-aut-sei=Sasaki en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuuraRyutaro en-aut-sei=Matsuura en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TomitaKoji en-aut-sei=Tomita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UmakoshiNoriyuki en-aut-sei=Umakoshi en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=MunetomoKazuaki en-aut-sei=Munetomo en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=SakuraiJun en-aut-sei=Sakurai en-aut-mei=Jun 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=NakazawaAtsushi en-aut-sei=Nakazawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MatsumiyaKiyoshi en-aut-sei=Matsumiya en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MatsunoTakayuki en-aut-sei=Matsuno en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KamegawaTetsushi en-aut-sei=Kamegawa en-aut-mei=Tetsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Collaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiology, Medical Development Field, 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 Radiology, Medical Development Field, Okayama University kn-affil= affil-num=9 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=10 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=11 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=13 en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=14 en-affil=Department of Medical Technology, Faculty of Life Science, Okayama University of Science kn-affil= affil-num=15 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=16 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Robot kn-keyword=Robot en-keyword=Needle kn-keyword=Needle en-keyword=Bone kn-keyword=Bone en-keyword=CT-guided kn-keyword=CT-guided en-keyword=Intervention kn-keyword=Intervention END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=10 article-no= start-page=1527 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Activation of TAS2R Signaling by Diphenidol Suppresses Tumor Growth and Remodels the Tumor Immune Microenvironment in Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Oral squamous cell carcinoma (OSCC) remains a clinically challenging malignancy characterized by aggressive behavior and limited therapeutic options. Bitter taste receptors (TAS2Rs), expressed across multiple tissues and cancer types, have recently emerged as regulators of tumor biology and immune responses; however, their functional significance in OSCC remains poorly understood. Methods: Immunohistochemical analysis was performed using surgically resected human tongue OSCC specimens and a tissue microarray (TMA) cohort. In parallel, four TAS2R agonists were evaluated in SCC7 cells to assess intracellular calcium responses. RNA sequencing was conducted to analyze transcriptional changes following diphenidol treatment, and functional assays, including proliferation, migration, and apoptosis analyses, were performed in vitro. Antitumor effects were further evaluated in a syngeneic SCC7 mouse model, followed by TUNEL staining and flow cytometry to assess apoptosis and immune cell infiltration. Results: TAS2R38 expression was markedly upregulated in dysplastic and invasive OSCC lesions with predominant nuclear localization and was associated with histological grade and clinical stage, indicating an early and sustained alteration during tumor progression. Among the agonists tested, diphenidol most strongly induced IP3-dependent intracellular Ca2+ elevation. RNA sequencing revealed upregulation of Il1rl1 and Lzts2. Functionally, diphenidol significantly suppressed SCC7 cell proliferation and migration and induced apoptosis in vitro. In vivo, diphenidol reduced tumor volume and weight and increased apoptotic activity. Flow cytometry demonstrated a marked reduction in tumor-infiltrating CD4+CD25+Foxp3+ regulatory T cells, indicating modulation of the tumor immune microenvironment. Conclusions: TAS2R activation by diphenidol suppresses tumor growth through both tumor-intrinsic mechanisms and modulation of the tumor immune microenvironment in OSCC. These findings define TAS2R-mediated calcium signaling as a novel axis linking tumor progression and immunoregulation. Given that diphenidol is a clinically approved drug with an established safety profile, our results provide a strong rationale for TAS2R-targeted drug repurposing strategies in cancer therapy. en-copyright= kn-copyright= en-aut-name=NasrunNisrina Ekayani en-aut-sei=Nasrun en-aut-mei=Nisrina Ekayani kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanimuraAkihiko en-aut-sei=Tanimura en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaKoki en-aut-sei=Yoshida en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UeharaOsamu en-aut-sei=Uehara en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HosoyaAkihiro en-aut-sei=Hosoya en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakebeHiroaki en-aut-sei=Takebe en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AbikoYoshihiro en-aut-sei=Abiko en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=RuslinMuhammad en-aut-sei=Ruslin en-aut-mei=Muhammad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShimoTsuyoshi en-aut-sei=Shimo en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=2 en-affil=Division of Pharmacology, Department of Oral Biology, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=3 en-affil=Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=4 en-affil=Division of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Division of Craniofacial Development and Tissue Biology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=8 en-affil=Division of Histology, Department of Oral Biology, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Hasanuddin University kn-affil= affil-num=12 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido kn-affil= en-keyword=bitter taste receptor kn-keyword=bitter taste receptor en-keyword=diphenidol kn-keyword=diphenidol en-keyword=immunometabolism kn-keyword=immunometabolism en-keyword=oral squamous cellcarcinoma kn-keyword=oral squamous cellcarcinoma en-keyword=TAS2R signaling kn-keyword=TAS2R signaling en-keyword=tumor immune microenvironment kn-keyword=tumor immune microenvironment END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=46 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Revised taxonomy reveals sustained introgression and secondary contact in ancient lake ricefishes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Biotic diversification in ancient lakes is shaped by complex geological histories and genetic exchange among populations. The Malili Lake system on Sulawesi Island represents a classic natural laboratory for studying freshwater fish evolution and harbors multiple endemic Oryzias species that diversified under repeated hydrological reorganizations. Previous genomic analyses inferred that two sympatric species in Lake Towuti (O. profundicola and O. loxolepis) experienced a single ancient introgression event from a gghost lineageh 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 gghost lineageh 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