start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=1 article-no= start-page=e70005 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=Lyme neuroborreliosis in Japan: Borrelia burgdorferi sensu lato as a cause of meningitis of previously undetermined etiology in hospitalized patients outside of the island of Hokkaido, 2010?2021 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Purpose: Clinical manifestations of Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl), include erythema migrans, Lyme neuroborreliosis (LNB), carditis, and arthritis. LB is a notifiable disease in Japan with <30 surveillance-reported LB cases annually, predominately from Hokkaido Prefecture. However, LB, including LNB, may be under-diagnosed in Japan since diagnostic tests are not readily available. We sought to determine if LNB could be a cause of previously undiagnosed encephalitis or meningitis in Japan.
Methods: Investigators at 15 hospitals in 10 prefectures throughout Japan retrieved serum and/or cerebrospinal fluid (CSF) samples collected in 2010?2021 from 517 patients hospitalized with encephalitis or meningitis which had an etiology that had not been determined. Samples were tested for Bbsl-specific antibodies using ELISA and Western blot tests. In alignment with the European Union LNB case definition, a confirmed LNB case had CSF pleocytosis and intrathecal production of Bbsl-specific antibodies and a probable LNB case had a CSF sample with pleocytosis and Bbsl-specific antibodies.
Results: LNB was identified in three hospitalized patients with meningitis of previously undetermined etiology: a male resident of Aomori Prefecture was a confirmed LNB case, and two female residents of Oita Prefecture were probable LNB cases. None of the patients with confirmed or probable LNB had traveled in the month prior to symptom onset and none had samples previously tested for LB.
Conclusion: The identification of previously undiagnosed LNB cases indicates a need for enhanced disease awareness in Japan, particularly beyond Hokkaido Island, and more readily available LB diagnostic testing. en-copyright= kn-copyright= en-aut-name=OhiraMasayuki en-aut-sei=Ohira en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakanoAi en-aut-sei=Takano en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshiKentaro en-aut-sei=Yoshi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AraiAkira en-aut-sei=Arai en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AsoYashuhiro en-aut-sei=Aso en-aut-mei=Yashuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FurutaniRikiya en-aut-sei=Furutani en-aut-mei=Rikiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamanoTadanori en-aut-sei=Hamano en-aut-mei=Tadanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Takahashi‐IwataIkuko en-aut-sei=Takahashi‐Iwata en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KanekoChikako en-aut-sei=Kaneko en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuuraTohru en-aut-sei=Matsuura en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaedaNorihisa en-aut-sei=Maeda en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakajimaHideto en-aut-sei=Nakajima en-aut-mei=Hideto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShindoKatsuro en-aut-sei=Shindo en-aut-mei=Katsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SuenagaToshihiko en-aut-sei=Suenaga en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= en-aut-name=SuzukiYasuhiro en-aut-sei=Suzuki en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=AnguloFrederick J. en-aut-sei=Angulo en-aut-mei=Frederick J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=EdwardsJuanita en-aut-sei=Edwards en-aut-mei=Juanita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=BenderCody Matthew en-aut-sei=Bender en-aut-mei=Cody Matthew kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HarperLisa R. en-aut-sei=Harper en-aut-mei=Lisa R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=NakayamaYoshikazu en-aut-sei=Nakayama en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=ItoShuhei en-aut-sei=Ito en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=PilzAndreas en-aut-sei=Pilz en-aut-mei=Andreas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=StarkJames H. en-aut-sei=Stark en-aut-mei=James H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=Mo?siJennifer C. en-aut-sei=Mo?si en-aut-mei=Jennifer C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=MizusawaHidehiro en-aut-sei=Mizusawa en-aut-mei=Hidehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=TakaoMasaki en-aut-sei=Takao en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Department of Clinical Laboratory and Internal Medicine, National Center of Neurology and Psychiatry kn-affil= affil-num=2 en-affil=Department of Veterinary Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University kn-affil= affil-num=3 en-affil=National Research Center for the Control and Prevention of Infectious Diseases, Nagasaki University kn-affil= affil-num=4 en-affil=Department of Neurology, Aomori Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Neurology, Oita Prefectural Hospital kn-affil= affil-num=6 en-affil=Department of Neurology, National Hospital Organization, Shinshu Ueda General Hospital kn-affil= affil-num=7 en-affil=Department of Neurology, University of Fukui Hospital kn-affil= affil-num=8 en-affil=Department of Neurology, Hokkaido University Hospital kn-affil= affil-num=9 en-affil=Department of Neurology, Southern Tohoku General Hospital kn-affil= affil-num=10 en-affil=Division of Neurology, Jichi Medical University kn-affil= affil-num=11 en-affil=Department of Neurology, National Hospital Organization Beppu Medical Center kn-affil= affil-num=12 en-affil=Department of Neurology, Nihon University Itabashi Hospital kn-affil= affil-num=13 en-affil=Department of Neurology, Kurashiki Central Hospital kn-affil= affil-num=14 en-affil=Department of Neurology, Tenri Hospital kn-affil= affil-num=15 en-affil=Department of Neurology, Nara Medical University Hospital kn-affil= affil-num=16 en-affil=Department of Neurology, National Hospital Organization Asahikawa Medical Center kn-affil= affil-num=17 en-affil=Department of Neurology, Okayama University Hospital kn-affil= affil-num=18 en-affil=Vaccines and Antivirals Medical Affairs, Pfizer Vaccines kn-affil= affil-num=19 en-affil=Vaccines and Antivirals Medical Affairs, Pfizer Vaccines kn-affil= affil-num=20 en-affil=Vaccines and Antivirals Medical Affairs, Pfizer Vaccines kn-affil= affil-num=21 en-affil=Vaccines and Antivirals Medical Affairs, Pfizer Vaccines kn-affil= affil-num=22 en-affil=Vaccines Medical Affairs, Pfizer Japan Inc kn-affil= affil-num=23 en-affil=Vaccines Medical Affairs, Pfizer Japan Inc kn-affil= affil-num=24 en-affil=Vaccines and Antivirals Medical Affairs, Pfizer Vaccines kn-affil= affil-num=25 en-affil=Vaccines and Antivirals Medical Affairs, Pfizer Vaccines kn-affil= affil-num=26 en-affil=Vaccines and Antivirals Medical Affairs, Pfizer Vaccines kn-affil= affil-num=27 en-affil=Department of Neurology, National Center of Neurology and Psychiatry kn-affil= affil-num=28 en-affil=Department of Clinical Laboratory and Internal Medicine, National Center of Neurology and Psychiatry kn-affil= en-keyword=epidemiology kn-keyword=epidemiology en-keyword=disease burden kn-keyword=disease burden en-keyword=Lyme neuroborreliosis kn-keyword=Lyme neuroborreliosis en-keyword=meningitis kn-keyword=meningitis en-keyword=tick-borne disease kn-keyword=tick-borne disease 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=2025 dt-pub=20250605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Determinants of residual myometrial thickness after cesarean delivery: Comparative analysis of barbed versus conventional sutures?A sub‐analysis from the SPIRAL trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: This sub-analysis aimed to determine whether conventional suture-associated risk factors for cesarean scar defect show similar outcomes with barbed continuous suturing, and to identify factors influencing residual myometrial thickness when using barbed continuous sutures.
Methods: This sub-analysis of a multicenter, parallel-group, randomized controlled trial across four Japanese obstetrics and gynecology departments included 1211 women who had their first cesarean delivery between May 2020 and March 2023. Among them, 298 women underwent a C-section, with 253 follow-up through July 2023. Singleton pregnancies were randomly assigned to receive either barbed or conventional double-layered continuous sutures in a 1:1 ratio; they were monitored from consent through their 6- to 7-month check-up. The effects of cervical ripening, facility characteristics, and surgeon experience were investigated using a two-way ANOVA.
Results: Of the remaining 253 patients, 33 were lost to follow-up and 220 completed follow-up (110 per group). One institution enrolled the largest proportion of participants (45.9%), whereas two other institutions had more experienced surgeons. Two-way ANOVA revealed that surgeon experience (P?=?0.020) and institutional factors (P? Conclusion: Institutional factors and surgeon experience represent significant determinants of residual myometrial thickness when using barbed sutures for cesarean closure, highlighting the importance of standardized surgical protocols and training across facilities. en-copyright= kn-copyright= en-aut-name=MakiJota en-aut-sei=Maki en-aut-mei=Jota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OobaHikaru en-aut-sei=Ooba en-aut-mei=Hikaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitomaTomohiro en-aut-sei=Mitoma en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakatoHikari en-aut-sei=Nakato en-aut-mei=Hikari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuemoriAyano en-aut-sei=Suemori en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuriyamaChiaki en-aut-sei=Kuriyama en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakataShujiro en-aut-sei=Sakata en-aut-mei=Shujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MishimaSakurako en-aut-sei=Mishima en-aut-mei=Sakurako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhiraAkiko en-aut-sei=Ohira en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=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 Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=barbed suture kn-keyword=barbed suture en-keyword=cervical ripening kn-keyword=cervical ripening en-keyword=cesarean scar defect kn-keyword=cesarean scar defect en-keyword=cesarean scar disorder kn-keyword=cesarean scar disorder en-keyword=niche kn-keyword=niche en-keyword=residual myometrial thickness kn-keyword=residual myometrial thickness en-keyword=risk factors kn-keyword=risk factors END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=30648 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250820 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of mechanical stretching stimulation on maturation of human iPS cell-derived cardiomyocytes co-cultured with human gingival fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the realm of regenerative medicine, despite the various techniques available for inducing the differentiation of induced pluripotent stem (iPS) cells into cardiomyocytes, there remains a need to enhance the maturation of the cardiomyocytes. This study aimed to improve the differentiation and subsequent maturation of iPS-derived cardiomyocytes (iPS-CMs) by incorporating mechanical stretching. Human iPS cells were co-cultured with human gingival fibroblasts (HGF) on a polydimethylsiloxane (PDMS) stretch chamber, where mechanical stretching stimulation was applied during the induction of cardiomyocyte differentiation. The maturation of iPS-CMs was assessed using qRT-PCR, immunocytochemistry, transmission electron microscopy, calcium imaging and contractility comparisons. Results indicated significantly elevated gene expression levels of cardiomyocyte markers (cTnT) and the mesodermal marker (Nkx2.5) in the stretch group compared to the control group. Fluorescent immunocytochemical staining revealed the presence of cardiac marker proteins (cTnT and MYL2) in both groups, with higher protein expression in the stretch group. Additionally, structural maturation of iPS-CMs in the stretch group was notably better than in the control group. A significant increase in the contractility and calcium cycle of iPS-CMs was observed in the stretch group. These findings demonstrate that mechanical stretching stimulation enhances the maturation of iPS-CMs co-cultured with HGF. en-copyright= kn-copyright= en-aut-name=WangMengxue en-aut-sei=Wang en-aut-mei=Mengxue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IdeiHarumi en-aut-sei=Idei en-aut-mei=Harumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangChen en-aut-sei=Wang en-aut-mei=Chen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiangYin en-aut-sei=Liang en-aut-mei=Yin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiuYun en-aut-sei=Liu en-aut-mei=Yun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsudaYusuke en-aut-sei=Matsuda en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiKen en-aut-sei=Takahashi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nursing, School of Life and Health Sciences, HuZhou College kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Human induced pluripotent stem cell kn-keyword=Human induced pluripotent stem cell en-keyword=Cardiomyocyte kn-keyword=Cardiomyocyte en-keyword=Human gingival fibroblast kn-keyword=Human gingival fibroblast en-keyword=Mechanical stretching kn-keyword=Mechanical stretching END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=16 article-no= start-page=7832 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synergistic Antimicrobial Activity of BrSPR20-P1 Peptide and Silver Nanoparticles Against Pathogenic Bacteria en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bacterial infection is a cause of life-threatening diseases. The emergence of antimicrobial-resistant bacteria exacerbates this situation, highlighting the need for the discovery of new antimicrobial agents. Our previous study identified a novel antimicrobial peptide, BrSPR20-P1 (P1), which showed potential activity against MRSA. Additionally, silver nanoparticles (AgNPs) exhibit broad-spectrum antibacterial activity, capable of killing multidrug-resistant bacteria. The combination of antimicrobial agents presents a novel strategy for combating these pathogens. This study aimed to evaluate the antibacterial activity of the combination of P1 and AgNPs. It revealed that the combinations showed synergy. The P1 and AgNP mixture at a concentration of 1 and 8 ?g/mL (1:8) doubled the activity against S. aureus and MRSA, while that combination of 64 and 64 ?g/mL (64:64) exhibited broad-spectrum activity, expanding to E. coli with a 32-fold increase. These combinations exhibited a bactericidal effect, showing the rapid killing of tested bacteria at 10× MIC, with killing rates during the first 3 h ranging from 4.04 ± 0.01 to 4.31 ± 0.03 h?1. The P1 and AgNP mixtures caused a low risk of antibacterial resistance up to 30 passages. It was demonstrated that the synergistic activity of P1 and AgNPs occurred through the disruption of cell walls and membranes, leakage of intracellular materials, and cell lysis. Additionally, the mixtures appeared to interact with bacterial genomic DNA, as indicated by a gel retardation assay. These activities of the combinations were concentration-dependent. The 1:8 ?g/mL mixture caused low hemolysis and cytotoxicity and did not impede the wound healing process. In contrast, although the 64:64 ?g/mL mixture showed excellent antibacterial efficacy, it was toxic to erythrocytes and mammalian cells. It implies that dose optimization is required to balance its efficacy and toxicity. Therefore, the P1 and AgNP combinations exhibit synergistic antimicrobial activity and have the potential to resolve bacterial infections. en-copyright= kn-copyright= en-aut-name=ThonginThanyamai en-aut-sei=Thongin en-aut-mei=Thanyamai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SawatdeeSomchai en-aut-sei=Sawatdee en-aut-mei=Somchai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SongnakaNuttapon en-aut-sei=Songnaka en-aut-mei=Nuttapon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=WiwasukuTheanchai en-aut-sei=Wiwasuku en-aut-mei=Theanchai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SrichanaTeerapol en-aut-sei=Srichana en-aut-mei=Teerapol kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakphengTitpawan en-aut-sei=Nakpheng en-aut-mei=Titpawan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AtipairinApichart en-aut-sei=Atipairin en-aut-mei=Apichart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil= School of Pharmacy, Walailak University kn-affil= affil-num=2 en-affil= School of Pharmacy, Walailak University kn-affil= affil-num=3 en-affil= School of Pharmacy, Walailak University kn-affil= affil-num=4 en-affil=Department of Bacteriology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=School of Science, Walailak University kn-affil= affil-num=6 en-affil=Drug Delivery System Excellence Center and Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University kn-affil= affil-num=7 en-affil=Drug Delivery System Excellence Center and Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University kn-affil= affil-num=8 en-affil= School of Pharmacy, Walailak University kn-affil= en-keyword=antimicrobial peptide kn-keyword=antimicrobial peptide en-keyword=Brevibacillus sp. SPR20 kn-keyword=Brevibacillus sp. SPR20 en-keyword=silver nanoparticle kn-keyword=silver nanoparticle en-keyword=synergistic effect kn-keyword=synergistic effect END start-ver=1.4 cd-journal=joma no-vol=104 cd-vols= no-issue=2 article-no= start-page=151495 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tri-culture model of intestinal epithelial cell, macrophage, and bacteria for the triggering of inflammatory bowel disease on a microfluidic device en-subtitle= kn-subtitle= en-abstract= kn-abstract=Inflammatory bowel disease (IBD) involves gastrointestinal inflammation, due to intestinal epithelial barrier destruction caused by excessive immune activation. Conventional cell culture systems do not provide a model system that can recapitulate the complex interactions between epithelial cells, immune cells, and intestinal bacteria. To address this, we developed a microfluidic device that mimics the inflammatory response associated with microbial invasion of the intestinal mucosa. The device consisted of two media channels, an upper and a lower channel, and a porous membrane between these channels on which C2BBe1 intestinal epithelial cells were seeded to form a tight junction layer. Each electrode was placed in contact with both channels to continuously monitor the tight junction state. Fresh medium flow allowed bacterial numbers to be controlled and bacterial toxins to be removed, allowing co-culture of mammalian cells and bacteria. In addition, RAW264 macrophage cells were attached to the bottom of the lower channel. By introducing E. coli into the lower channel, the RAW264 cells were activated and produced TNF-α, successfully recapitulating a culture model of inflammation in which the C2BBe1cell tight junction layer was destroyed. The main structure of the device was initially made of polydimethylsiloxane to facilitate its widespread use, but with a view to introducing anaerobic bacteria in the future, a similar phenomenon was successfully reproduced using polystyrene. When TPCA-1, an IκB kinase 2 inhibitor was added into this IBD culture model, the tight junction destruction was significantly suppressed. The results suggest that this IBD culture model also is useful as a screening system for anti-IBD drugs. en-copyright= kn-copyright= en-aut-name=TamuraShiori en-aut-sei=Tamura en-aut-mei=Shiori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PasangClarissa Ellice Talitha en-aut-sei=Pasang en-aut-mei=Clarissa Ellice Talitha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsudaMinami en-aut-sei=Tsuda en-aut-mei=Minami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaShilan en-aut-sei=Ma en-aut-mei=Shilan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShindoHiromasa en-aut-sei=Shindo en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=OhkuboTomoki en-aut-sei=Ohkubo en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiyamaYoichi en-aut-sei=Fujiyama en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TamaiMiho en-aut-sei=Tamai en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TagawaYoh-ichi en-aut-sei=Tagawa en-aut-mei=Yoh-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=2 en-affil=School of Life Science and Technology, Tokyo Institute of Technology kn-affil= affil-num=3 en-affil=School of Life Science and Technology, Tokyo Institute of Technology kn-affil= affil-num=4 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=School of Life Science and Technology, Tokyo Institute of Technology kn-affil= affil-num=6 en-affil=Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Biology-Chemistry Unit, Technology Research Laboratory, Shimadzu Corporation kn-affil= affil-num=8 en-affil=Biology-Chemistry Unit, Technology Research Laboratory, Shimadzu Corporation kn-affil= affil-num=9 en-affil=School of Life Science and Technology, Tokyo Institute of Technology kn-affil= affil-num=10 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= en-keyword=Intestine chip kn-keyword=Intestine chip en-keyword=Inflammatory bowel disease kn-keyword=Inflammatory bowel disease en-keyword=Co-culture kn-keyword=Co-culture en-keyword=Tri-culture kn-keyword=Tri-culture en-keyword=Fluidic device kn-keyword=Fluidic device en-keyword=Disease model kn-keyword=Disease model en-keyword=Macrophage kn-keyword=Macrophage en-keyword=Inflammation kn-keyword=Inflammation END start-ver=1.4 cd-journal=joma no-vol=272 cd-vols= no-issue=1 article-no= start-page=36 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genetic and functional analyses of SPTLC1 in juvenile amyotrophic lateral sclerosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of the motor system. Pathogenic variants in SPTLC1, encoding a subunit of serine palmitoyltransferase, cause hereditary sensory and autonomic neuropathy type 1 (HSAN1), and have recently been associated with juvenile ALS. SPTLC1 variants associated with ALS cause elevated levels of sphinganines and ceramides. Reports on ALS associated with SPTLC1 remain limited. This study aimed to investigate the frequency of SPTLC1 variants in ALS and relevant clinical characteristics.
Methods We analyzed whole-exome and whole-genome sequence data from 40 probands with familial ALS and 413 patients with sporadic ALS without previously identified causative variants. Reverse transcription polymerase chain reaction (RT-PCR) analysis and droplet digital PCR (ddPCR) were used to assess splicing and mosaicism, respectively. Plasma sphingolipid levels were quantified to analyze biochemical consequences.
Results The heterozygous c.58G>A, p.Ala20Thr variant was identified in a 21-year-old Japanese female patient presenting with symmetric weakness which slowly progressed over 15 years. RT-PCR analysis showed no splice defects. Plasma sphingolipid levels in the patient were significantly increased compared to her asymptomatic parents. ddPCR revealed that the asymptomatic father harbored a mosaic variant with 17% relative mutant allele abundance in peripheral blood leukocytes.
Conclusions We identified a pathogenic c.58G>A, p.Ala20Thr SPTLC1 variant in a patient with juvenile ALS, likely inherited from an asymptomatic parent with mosaicism. Lipid analysis results are consistent with previous findings on SPTLC1-associated ALS. Further studies are necessary to determine the clinical effect of mosaic variants of SPTLC1. en-copyright= kn-copyright= en-aut-name=OkuboSo en-aut-sei=Okubo en-aut-mei=So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SudoAtsushi en-aut-sei=Sudo en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EsakiKayoko en-aut-sei=Esaki en-aut-mei=Kayoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatakeWataru en-aut-sei=Satake en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=GreimelPeter en-aut-sei=Greimel en-aut-mei=Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShingaiNanoka en-aut-sei=Shingai en-aut-mei=Nanoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OyaYasushi en-aut-sei=Oya en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YoshikawaTakeo en-aut-sei=Yoshikawa en-aut-mei=Takeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Biotechnology and Life Sciences, Faculty of Biotechnology and Life Sciences, Sojo University kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Laboratory for Cell Function Dynamics, RIKEN Centre for Brain Sciences kn-affil= affil-num=10 en-affil=Division of Applied Life Science, Graduate School of Engineering, Sojo University kn-affil= affil-num=11 en-affil=Department of Neurology, National Center of Neurology and Psychiatry kn-affil= affil-num=12 en-affil=Laboratory of Molecular Psychiatry, RIKEN Center for Brain Science kn-affil= affil-num=13 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=Juvenile amyotrophic lateral sclerosis kn-keyword=Juvenile amyotrophic lateral sclerosis en-keyword=SPTLC1 kn-keyword=SPTLC1 en-keyword=Sphingolipids kn-keyword=Sphingolipids en-keyword=Mosaicism kn-keyword=Mosaicism END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=15 article-no= start-page=e71098 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real‐World Data of Comprehensive Cancer Genomic Profiling Tests Performed in the Routine Clinical Setting in Sarcoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Next-generation sequencing-based comprehensive cancer genomic profiling (CGP) tests are beneficial for refining diagnosis and personalized treatment of various cancers. However, the clinical impact of CGP, as covered by public health insurance in the management of sarcomas, remains unknown. Especially, the data on the utility of the newly emerging dual DNA?RNA panel compared to the conventional DNA-only panel in clinical settings is lacking. Therefore, we evaluated the utility of CGP in routine clinical practice for sarcoma treatment.
Patients and Methods: In this study, three types of DNA panel and one DNA?RNA panel, reimbursed by Japanese public health insurance, were utilized. We detected oncogenic and druggable gene mutations and genotype-matched therapies.
Results: One hundred and thirty-six patients were included in this study. Based on the detection of highly histology-specific translocations in the sequencing results, 2.2% of patients were re-classified. In patients with translocation-related sarcomas, a DNA?RNA panel identified more histology-specific fusion genes than DNA panels (p?=?0.0035). Specifically, 86.8% and 39.0% of patients had oncogenic and druggable genomic alterations, respectively. Of these, 9.6% underwent genotype-matched therapy, with a 36.3% response rate and an 81.8% disease control rate. Patients who were administered genomically matched therapy had better overall survival (OS) than those who did not in patients with metastatic or advanced sarcoma with no prior chemotherapy (3-year OS: 83.3% vs. 48.0%, p?=?0.42). Patients with TP53 and RB1 mutations had worse OS than those without. Germline findings were detected in 11.0% of the patients, one of whom had a truly germline origin.
Conclusions: This study suggests that publicly reimbursed CGP tests, particularly the dual DNA?RNA panel, could be beneficial for refining diagnostic precision in selected sarcoma subtypes, treatment decisions, detecting the germline findings, and prognosis prediction in routine clinical settings for sarcoma. The implementation of genotype-matched therapies showed favorable clinical outcomes and improved the prognosis. en-copyright= kn-copyright= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OsoneTatsunori en-aut-sei=Osone en-aut-mei=Tatsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=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=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FutagawaMashu en-aut-sei=Futagawa en-aut-mei=Mashu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShimoiTatsunori en-aut-sei=Shimoi en-aut-mei=Tatsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 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=15 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 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=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Center for Comprehensive Genomic Medicine, 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= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Medical Oncology, National Cancer Center Hospital kn-affil= affil-num=13 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Center for Clinical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=genotype-matched therapy kn-keyword=genotype-matched therapy en-keyword=multiplex gene panel test kn-keyword=multiplex gene panel test en-keyword=sarcoma kn-keyword=sarcoma END start-ver=1.4 cd-journal=joma no-vol=638 cd-vols= no-issue=8049 article-no= start-page=225 end-page=236 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immune evasion through mitochondrial transfer in the tumour microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T?cell attack1. For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumour immune responses2,3,4. However, detailed mechanisms of such processes remain unclear. Here we analyse clinical specimens and identify mitochondrial DNA (mtDNA) mutations in TILs that are shared with cancer cells. Moreover, mitochondria with mtDNA mutations from cancer cells are able to transfer to TILs. Typically, mitochondria in TILs readily undergo mitophagy through reactive oxygen species. However, mitochondria transferred from cancer cells do not undergo mitophagy, which we find is due to mitophagy-inhibitory molecules. These molecules attach to mitochondria and together are transferred to TILs, which results in homoplasmic replacement. T?cells that acquire mtDNA mutations from cancer cells exhibit metabolic abnormalities and senescence, with defects in effector functions and memory formation. This in turn leads to impaired antitumour immunity both in vitro and in vivo. Accordingly, the presence of an mtDNA mutation in tumour tissue is a poor prognostic factor for immune checkpoint inhibitors in patients with melanoma or non-small-cell lung cancer. These findings reveal a previously unknown mechanism of cancer immune evasion through mitochondrial transfer and can contribute to the development of future cancer immunotherapies. en-copyright= kn-copyright= en-aut-name=IkedaHideki en-aut-sei=Ikeda en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaseKatsushige en-aut-sei=Kawase en-aut-mei=Katsushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiTatsuya en-aut-sei=Nishi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=TakenagaKeizo en-aut-sei=Takenaga en-aut-mei=Keizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AkiSho en-aut-sei=Aki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=LinJason en-aut-sei=Lin en-aut-mei=Jason kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawashimaShusuke en-aut-sei=Kawashima en-aut-mei=Shusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SuzukiShinichiro en-aut-sei=Suzuki en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MakinoshimaHideki en-aut-sei=Makinoshima en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ItamiMakiko en-aut-sei=Itami en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NakamuraYuki en-aut-sei=Nakamura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TatsumiYasutoshi en-aut-sei=Tatsumi en-aut-mei=Yasutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SuenagaYusuke en-aut-sei=Suenaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MorinagaTakao en-aut-sei=Morinaga en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=Honobe-TabuchiAkiko en-aut-sei=Honobe-Tabuchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=OhnumaTakehiro en-aut-sei=Ohnuma en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KawamuraTatsuyoshi en-aut-sei=Kawamura en-aut-mei=Tatsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=UmedaYoshiyasu en-aut-sei=Umeda en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=NakamuraYasuhiro en-aut-sei=Nakamura en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KiniwaYukiko en-aut-sei=Kiniwa en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 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=26 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=27 ORCID= en-aut-name=IkedaJun-ichiro en-aut-sei=Ikeda en-aut-mei=Jun-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=HanazawaToyoyuki en-aut-sei=Hanazawa en-aut-mei=Toyoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 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=30 ORCID= en-aut-name=ManoHiroyuki en-aut-sei=Mano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 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=32 ORCID= en-aut-name=OsawaTsuyoshi en-aut-sei=Osawa en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=KawazuMasahito en-aut-sei=Kawazu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 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=35 ORCID= affil-num=1 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=2 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=3 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Division of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute kn-affil= affil-num=6 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=7 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Division of Nutriomics and Oncology, RCAST, The University of Tokyo kn-affil= affil-num=9 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=10 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan Department of Dermatology, Graduate School of Medicine, Chiba University kn-affil= affil-num=11 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Tsuruoka Metabolomics Laboratory, National Cancer Center kn-affil= affil-num=15 en-affil=Department of Surgical Pathology, Chiba Cancer Center kn-affil= affil-num=16 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=17 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=18 en-affil=Laboratory of Evolutionary Oncology, Chiba Cancer Center Research Institute kn-affil= affil-num=19 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=20 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=21 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=22 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=23 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=24 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=25 en-affil=Department of Dermatology, Shinshu University School of Medicine kn-affil= affil-num=26 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=27 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=28 en-affil=Department of Diagnostic Pathology, Graduate School of Medicine, Chiba University kn-affil= affil-num=29 en-affil=Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine kn-affil= affil-num=30 en-affil=Department of General Thoracic Surgery and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=31 en-affil=Division of Cellular Signalling, National Cancer Center Research Institute kn-affil= affil-num=32 en-affil=Department of Respirology, Graduate School of Medicine, Chiba University kn-affil= affil-num=33 en-affil=Division of Nutriomics and Oncology, RCAST, The University of Tokyo kn-affil= affil-num=34 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=35 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue= article-no= start-page=1477 end-page=1486 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250719 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Predictive Value of Tumor ERCC1 Expression for Treatment Outcomes After Adjuvant Chemotherapy in Patients with Completely Resected Non-Small Cell Lung Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: To evaluate the predictive value of tumor expression of the excision repair cross-complementation group 1 gene (ERCC1) for the treatment outcomes after platinum-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC).
Methods: In this study, we conducted immunohistochemical analysis using a mouse monoclonal anti-ERCC1 antibody (clone 8F1) of operative specimens obtained from 238 patients enrolled in the SLCG0401 study which compared paclitaxel plus carboplatin (CBDCA+PTX) with uracil-tegafur (UFT) as adjuvant chemotherapy for stage IB-IIIA NSCLC. The overall survival (OS) of the patients was compared according to the ERCC1 expression status and adjuvant chemotherapy employed.
Results: Of the 238 specimens, 102 (42.9%) showed a positive result for ERCC1 expression. There were no significant differences in the patient characteristics or OS between the tumor ERCC1-positive and -negative patient groups. Among the patients with ERCC1-negative tumors, there was no significant difference in the survival between patient groups treated with CBDCA+PTX and UFT (HR=0.932, 95% CI: 0.52? 1.67, p=0.814). However, among the patients with ERCC1-positive tumors, CBDCA+PTX treatment tended to yield an inferior outcome, in terms of the OS, as compared with UFT treatment (HR=1.852, 95% CI: 0.92? 3.73, p=0.080). Multivariate analysis showed that ERCC1 expression was not an independent predictor of the OS following CBDCA+PTX treatment in completely resected NSCLC patients.
Conclusion: In completely resected NSCLC patients with positive tumor ERCC1 expression, adjuvant CBDCA+PTX treatment tended to yield an inferior outcome as compared with UFT treatment in terms of the OS. However, immunohistochemical analysis with the 8F1 antibody cannot be used for clinical decision making at this point. en-copyright= kn-copyright= en-aut-name=NakataMasao en-aut-sei=Nakata en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaishoShinsuke en-aut-sei=Saisho en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkumuraNorihito en-aut-sei=Okumura en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraHiroshige en-aut-sei=Nakamura en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=DateHiroshi en-aut-sei=Date en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery, Kawasaki Medical School kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, Kurashiki Central Hospital kn-affil= affil-num=5 en-affil=Division of General Thoracic Surgery and Breast and Endocrine Surgery, Department of Surgery, Faculty of Medicine, Tottori University kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Thoracic Surgery, Kyoto University Graduate School of Medicine kn-affil= en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=postoperative adjuvant chemotherapy kn-keyword=postoperative adjuvant chemotherapy en-keyword=platinum-based chemotherapy kn-keyword=platinum-based chemotherapy en-keyword=excision repair crosscomplementation group 1 gene kn-keyword=excision repair crosscomplementation group 1 gene en-keyword=survival kn-keyword=survival END start-ver=1.4 cd-journal=joma no-vol=409 cd-vols= no-issue=1 article-no= start-page=356 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241125 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Subjective global assessment for nutritional screening and its impact on surgical outcomes: A prospective study in older patients with colorectal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Our perioperative management center provides preoperative intervention and functional and nutritional assessments for colorectal cancer patients aged over 75 years. This study evaluated the associations of preoperative nutritional status with postoperative outcomes and prognosis in colorectal cancer patients aged 75 years or older.
Methods This was a prospective, observational study of 71 colorectal cancer patients aged 75 years or older who underwent surgery between July 2020 and September 2022. The Subjective Global Assessment (SGA) was evaluated as a nutritional index. The patients were classified into three groups: SGA-A (well nourished), B (moderately malnourished), and C (severely malnourished), and the correlations with postoperative outcomes and prognosis were examined.
Results The median age of the 71 patients (34 males, 37 females) was 78 (75?92) years, and their median body mass index (BMI) was 22.3 (13.4?31.9) kg/m2. Forty-eight patients had colon cancer, and 23 had rectal cancer. On the SGA, 28 patients were SGA-A, 25 SGA-B, and 18 SGA-C. The SGA-B/C group had significantly higher BMI (p? Conclusion The SGA is a promising nutritional index associated with short-term outcomes in older patients undergoing colorectal cancer surgery. The SGA can be assessed in a few minutes during an outpatient visit, making it useful for routine clinical use. 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=YoshidaYusuke en-aut-sei=Yoshida en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KondoYoshitaka en-aut-sei=Kondo en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TamuraRie en-aut-sei=Tamura en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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= affil-num=9 en-affil=Perioperative Management Center, Okayama University Hospital kn-affil= affil-num=10 en-affil=Perioperative Management Center, Okayama University Hospital kn-affil= affil-num=11 en-affil=Perioperative Management Center, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Subjective global assessment kn-keyword=Subjective global assessment en-keyword=Colorectal cancer kn-keyword=Colorectal cancer en-keyword=Older patients kn-keyword=Older patients en-keyword=Surgical outcome kn-keyword=Surgical outcome END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=6 article-no= start-page=1008 end-page=1016 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240422 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High risk of multiple gastric cancers in Japanese individuals with Lynch syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim: Lynch syndrome (LS) is a dominantly inherited syndrome characterized by an increased risk for LS associated tumors such as colorectal cancer (CRC) and gastric cancer (GC). However, the clinical benefit of surveillance for GC remains unclear while it has already been recommended for CRC. This study aimed to elucidate the clinical features of GC in Japanese individuals with LS, and the risk of developing multiple GCs to build regional-tailored surveillance programs in LS patients with GC.
Methods: Data on Japanese individuals with LS were retrospectively collected from a single institution. The clinical features of GC, including the cumulative risk of multiple GCs, were analyzed.
Results: Among 96 individuals with LS (MLH1/MSH2/MSH6, 75:20:1), 32 GC lesions were detected in 15 individuals with LS (male/female, 11:4). The median age at initial GC diagnosis was 52.7?y (range: 28?71). Histological examination revealed a predominance of intestinal type (19/24: 87.5%). Moreover, the majority of the GC lesions (82%) were determined to have high-frequency of microsatellite instability. The cumulative risk of individuals with LS developing GC at 70?y was 31.3% (MLH1 36.1%, MSH2 18.0%). Notably, the cumulative risk of individuals with LS developing metachronous and/or synchronous GCs at 0, 10 and 20?y after initial diagnosis of GC was 26.7%, 40.7%, and 59.4%, respectively.
Conclusion: Due to a higher risk of developing multiple GCs, intensive surveillance might be especially recommended for Japanese individuals with LS associated initial GC. 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=van SchaikThijs A. en-aut-sei=van Schaik en-aut-mei=Thijs A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=SatoYumiko en-aut-sei=Sato en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuganoKokichi en-aut-sei=Sugano en-aut-mei=Kokichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=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= 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 Neurosurgery, Brigham and Women's Hospital, Harvard Medical School kn-affil= affil-num=3 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=4 en-affil=Department of Pathology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=5 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center 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 Genetic Medicine, Kyoundo Hospital, SSasaki Foundation kn-affil= affil-num=8 en-affil=Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center kn-affil= affil-num=9 en-affil=Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=10 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= en-keyword=cumulative risk kn-keyword=cumulative risk en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=Japanese individuals kn-keyword=Japanese individuals en-keyword=Lynch syndrome kn-keyword=Lynch syndrome en-keyword=multiple gastric cancers kn-keyword=multiple gastric cancers END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=5 article-no= start-page=271 end-page=277 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240329 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Japan MSA registry: A multicenter cohort study of multiple system atrophy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure and various motor symptoms. While MSA-C (cerebellar type) predominates in East Asia, MSA-P (parkinsonian type) predominates in Europe and North America. This nationwide patient registry aimed to (1) conduct a prospective natural history study of MSA in Japan, (2) facilitate patient recruitment for clinical trials, and (3) deposit bioresources and clinical information in a biobank.
Methods: Thirteen institutions participated in this study. Clinical information was obtained by neurologists from the patients visiting the hospital every 12?months to assess the UMSARS Part 2 scores and by telephone interviews by nurses every 6?months to assess UMSARS Part 1 scores and to determine whether clinical events had occurred.
Results: Demographic data from 329 MSA patients (216 MSA-C and 113 MSA-P) were analyzed. The mean age at symptom onset was 58.2?years (standard deviation, 8.9); the mean duration of symptoms at enrollment was 3.5?years (standard deviation, 2.2). The mean 12-month changes in the UMSARS Part 1 and Part 2 scores were 7.9 (standard deviation, 5.6) and 6.4 (standard deviation, 5.9), respectively. The patient registry proved useful in recruiting participants for clinical trials, including those with gene variants. Clinical information and biospecimens were deposited in a biobank.
Discussion: The study highlighted the importance of telephone interviews in minimizing drop-out rates in natural history studies and demonstrated similar MSA progression rates across populations. The deposited bioresources are available to researchers upon request, aiming to contribute to future MSA researches. en-copyright= kn-copyright= en-aut-name=ChikadaAyaka en-aut-sei=Chikada en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OrimoKenta en-aut-sei=Orimo en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MizusawaHidehiro en-aut-sei=Mizusawa en-aut-mei=Hidehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakahashiYuji en-aut-sei=Takahashi en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatsunoMasahisa en-aut-sei=Katsuno en-aut-mei=Masahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaraKazuhiro en-aut-sei=Hara en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OnoderaOsamu en-aut-sei=Onodera en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IshiharaTomohiko en-aut-sei=Ishihara en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TadaMasayoshi en-aut-sei=Tada en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KuwabaraSatoshi en-aut-sei=Kuwabara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= en-aut-name=YamanakaYoshitaka en-aut-sei=Yamanaka en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakahashiRyosuke en-aut-sei=Takahashi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SawamotoNobukatsu en-aut-sei=Sawamoto en-aut-mei=Nobukatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SakatoYusuke en-aut-sei=Sakato en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IshimotoTomoyuki en-aut-sei=Ishimoto en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HanajimaRitsuko en-aut-sei=Hanajima en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=WatanabeYasuhiro en-aut-sei=Watanabe en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TakigawaHiroshi en-aut-sei=Takigawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=AdachiTadashi en-aut-sei=Adachi en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TakashimaHiroshi en-aut-sei=Takashima en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=HigashiKeiko en-aut-sei=Higashi en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KiraJunichi en-aut-sei=Kira en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=YabeIchiro en-aut-sei=Yabe en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=MatsushimaMasaaki en-aut-sei=Matsushima en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=OgataKatsuhisa en-aut-sei=Ogata en-aut-mei=Katsuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=IshikawaKinya en-aut-sei=Ishikawa en-aut-mei=Kinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=NishidaYoichiro en-aut-sei=Nishida en-aut-mei=Yoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=IshiguroTaro en-aut-sei=Ishiguro en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=OzakiKokoro en-aut-sei=Ozaki en-aut-mei=Kokoro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=NagataTetsuya en-aut-sei=Nagata en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Neurology, Nagoya University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Neurology, Nagoya University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=12 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=13 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=15 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=16 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=17 en-affil=Department of Neurology, Kyoto University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Human Health Sciences, Kyoto University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Neurology, Kyoto University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Neurology, Kyoto University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University kn-affil= affil-num=22 en-affil=Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University kn-affil= affil-num=23 en-affil=Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University kn-affil= affil-num=24 en-affil=Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University kn-affil= affil-num=25 en-affil=Department of Neurology, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=26 en-affil=Department of Neurology, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=27 en-affil=Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=28 en-affil=Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=29 en-affil=Department of Neurology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=30 en-affil=Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=31 en-affil=Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=32 en-affil=Department of Neurology, Higashi-Saitama National Hospital kn-affil= affil-num=33 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=34 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=35 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=36 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=37 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=38 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=multicenter cohort study kn-keyword=multicenter cohort study en-keyword=multiple system atrophy kn-keyword=multiple system atrophy en-keyword=natural history kn-keyword=natural history en-keyword=patient registry kn-keyword=patient registry END start-ver=1.4 cd-journal=joma no-vol=508 cd-vols= no-issue= article-no= start-page=111242 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enhanced aboveground biomass density estimation in Central Vietnamese forests en-subtitle= kn-subtitle= en-abstract= kn-abstract=Accurate estimation of spatially explicit forest aboveground biomass density (AGBD) is essential for supporting climate change mitigation strategies. Recent studies have demonstrated the predictive effectiveness of the random forest (RF) algorithm in forest AGBD estimation utilizing multi-source remote sensing (RS) data. However, the RF-based estimates may be further enhanced by integrating RF with kriging techniques that account for spatial autocorrelation in model residuals. Therefore, we investigated the performance of random forest ordinary kriging (RFOK) and random forest co-kriging (RFCK) for estimating AGBD in Central Vietnamese forests using Advanced Land Observing Satellite-2 Phased Array L-band Synthetic Aperture Radar-2 (ALOS-2 PALSAR-2), Sentinel-1 (S1), and Sentinel-2 (S2) imageries. 277 predictors, including spectral bands, radar backscatter coefficients, vegetation indices, biophysical variables, and texture metrics, were derived from these RS datasets and statistically linked to field measurements from 104 geo-referenced forest inventory plots. The results showed that textures, modified chlorophyll absorption ratio index (MCARI), and radar backscatters were key contributors to AGBD variability. The fusion of ALOS-2 PALSAR-2 and S2 data yielded the highest RF performance, with coefficient of determination (R2), root mean square error (RMSE), and mean absolute error (MAE) achieving 0.75, 39.15 t.ha-1, and 32.20 t.ha-1, respectively. Incorporating interpolated residuals by ordinary kriging and co-kriging into RF predictions enhanced estimation accuracy, with relative improvements of 5.74?7.04 % in R2, 8.73?10.91 % in RMSE, and 13.62?15.27 % in MAE, yet these gains remained limited. Although RFOK achieved marginally better accuracy (R2 = 0.80, RMSE = 34.88 t.ha-1, MAE = 27.28 t.ha-1) compared to RFCK (R2 = 0.79, RMSE = 35.73 t.ha-1, MAE = 27.81 t.ha-1), the latter reduced estimation bias more effectively, likely due to the inclusion of elevation as a covariate in the co-kriging process. These findings underscore the potential of the hybrid RF-kriging frameworks for improving spatial AGBD estimation, offering a robust approach for carbon accounting in tropical ecosystems. en-copyright= kn-copyright= en-aut-name=HoViet Hoang en-aut-sei=Ho en-aut-mei=Viet Hoang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoritaHidenori en-aut-sei=Morita en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BachoferFelix en-aut-sei=Bachofer en-aut-mei=Felix kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HoThanh Ha en-aut-sei=Ho en-aut-mei=Thanh Ha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=German Aerospace Center (DLR), Earth Observation Center kn-affil= affil-num=4 en-affil=University of Agriculture and Forestry, Hue University kn-affil= en-keyword=Forest aboveground biomass density kn-keyword=Forest aboveground biomass density en-keyword=Random forest kn-keyword=Random forest en-keyword=Ordinary kriging kn-keyword=Ordinary kriging en-keyword=Co-kriging kn-keyword=Co-kriging en-keyword=Multispectral kn-keyword=Multispectral en-keyword=Multi-frequency synthetic aperture radar kn-keyword=Multi-frequency synthetic aperture radar END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=5 article-no= start-page=1554 end-page=1577 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250405 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of geostatistics, machine learning algorithms, and their hybrid approaches for modeling soil organic carbon density in tropical forests en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Understanding the spatial variability of soil organic carbon density (SOCD) in tropical forests is necessary for efficient climate change mitigation initiatives. However, accurately modeling SOCD in these landscapes is challenging due to low-density sampling efforts and the limited availability of in-situ data caused by constrained accessibility. In this study, we aimed to explore the most suitable modeling technique for SOCD estimation in the context of tropical forest ecosystems.
Methods To support the research, thirty predictor covariates derived from remote sensing data, topographic attributes, climatic factors, and geographic positions were utilized, along with 104 soil samples collected from the top 30 cm of soil in Central Vietnamese tropical forests. We compared the effectiveness of geostatistics (ordinary kriging, universal kriging, and kriging with external drift), machine learning (ML) algorithms (random forest and boosted regression tree), and their hybrid approaches (random forest regression kriging and boosted regression tree regression kriging) for the prediction of SOCD. Prediction accuracy was evaluated using the coefficient of determination (R2), the root mean squared error (RMSE), and the mean absolute error (MAE) obtained from leave-one-out cross-validation.
Results The study results indicated that hybrid approaches performed best in predicting forest SOCD with the greatest values of R2 and the lowest values of MAE and RMSE, and the ML algorithms were more accurate than geostatistics. Additionally, the prediction maps produced by the hybridization showed the most realistic SOCD pattern, whereas the kriged maps were prone to have smoother patterns, and ML-based maps were inclined to possess more detailed patterns. The result also revealed the superiority of the ML plus residual kriging approaches over the ML models in reducing the underestimation of large SOCD values in high-altitude mountain areas and the overestimation of low SOCD values in low-lying terrain areas.
Conclusion Our findings suggest that the hybrid approaches of geostatistics and ML models are most suitable for modeling SOCD in tropical forests. en-copyright= kn-copyright= en-aut-name=HoViet Hoang en-aut-sei=Ho en-aut-mei=Viet Hoang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoritaHidenori en-aut-sei=Morita en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HoThanh Ha en-aut-sei=Ho en-aut-mei=Thanh Ha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BachoferFelix en-aut-sei=Bachofer en-aut-mei=Felix kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NguyenThi Thuong en-aut-sei=Nguyen en-aut-mei=Thi Thuong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=University of Agriculture and Forestry, Hue University kn-affil= affil-num=4 en-affil=German Aerospace Center (DLR), Earth Observation Center kn-affil= affil-num=5 en-affil=University of Agriculture and Forestry, Hue University kn-affil= en-keyword=Digital soil mapping kn-keyword=Digital soil mapping en-keyword=Hybrid approaches kn-keyword=Hybrid approaches en-keyword=Kriging kn-keyword=Kriging en-keyword=Machine learning kn-keyword=Machine learning en-keyword=Soil organic carbon density kn-keyword=Soil organic carbon density en-keyword=Tropical forests kn-keyword=Tropical forests END start-ver=1.4 cd-journal=joma no-vol=88 cd-vols= no-issue=9 article-no= start-page=1398 end-page=1405 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240823 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Morphological Features of Patent Foramen Ovale Compared Between Older and Young Patients With Cryptogenic Ischemic Stroke en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The morphology of a patent foramen ovale (PFO) with a high-risk for cryptogenic ischemic stroke (CS) is an important factor in the selection of patients for transcatheter closure, but the morphological features of PFO in older patients with a history of CS are less known because the most data are obtained from younger patients.
Methods and Results: The study included 169 patients who had a history of CS and PFO. The prevalence of high-risk morphologies of PFO assessed by transesophageal echocardiography was compared between patients aged ?60 years and patients aged <60 years. We also assessed the presence of septal malalignment of PFO on the aortic wall. The probability of CS due to PFO was evaluated using the PFO-Associated Stroke Causal Likelihood classification system. Patients aged ?60 years had a significantly higher prevalence of atrial septal aneurysm than patients aged <60 years. The prevalence of large right-to-left shunt, long-tunnel of PFO, or Eustachian valve or Chiari’s network was similar between patients aged ?60 years and <60 years. Septal malalignment was observed more frequently in patients aged ?60 years than in those <60 years old. Nearly 90% of patients aged ?60 years were classified as ‘possible’ in the PFO-Associated Stroke Causal Likelihood classification system.
Conclusions: High-risk morphologies of PFO are common in older patients with a history of CS, as well as in younger patients. en-copyright= kn-copyright= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakayaYoichi en-aut-sei=Takaya en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakayamaRie en-aut-sei=Nakayama en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsujiMasahiro en-aut-sei=Tsuji en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkagiTeiji en-aut-sei=Akagi en-aut-mei=Teiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MikiTakashi en-aut-sei=Miki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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 Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Cryptogenic ischemic stroke kn-keyword=Cryptogenic ischemic stroke en-keyword=Older patients kn-keyword=Older patients en-keyword=Patent foramen ovale kn-keyword=Patent foramen ovale END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=3 article-no= start-page=79 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association of the expression of 5?FU biomarkers with aging and prognosis in elderly patients with lung cancer treated with S?1 adjuvant chemotherapy: Follow?up results of the Setouchi Lung Cancer Group Study 1201 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Managing elderly patients presents several challenges because of age?related declines; however, age should not be the sole determinant for adjuvant treatment decisions in patients with non?small cell lung cancer (NSCLC). Moreover, age may affect the expression of 5?fluorouracil (5?FU) biomarkers. The present study assessed: i) The effect of age on the expression levels of 5?FU biomarkers by analyzing a public database; and ii) the ability of these biomarkers to predict clinical outcomes in elderly patients with NSCLC who underwent complete resection in the Setouchi Lung Cancer Group Study 1201 (SCLG1201) followed by S?1 adjuvant chemotherapy. Changes in gene expression levels across age groups were assessed by analyzing The Cancer Genome Atlas (TCGA) database. The expression of 5?FU biomarkers, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, epidermal growth factor receptor (EGFR) and excision repair cross?complementation group 1 (ERCC1), were assessed via quantitative reverse?transcription PCR assays in 89 elderly patients (?75 years) with NSCLC who received adjuvant chemotherapy with oral fluoropyrimidine prodrug S?1 in the SLCG1201 trial. TCGA database analysis (n=955) showed that TS expression decreased significantly with aging, especially in the age group ?75. In the SCLG1201 trial, univariate analysis revealed that EGFR upregulation and TS downregulation were correlated with favorable recurrence?free survival (RFS) and overall survival (OS), respectively. Multivariate analysis demonstrated that pathological stage was an independent prognostic factor for both RFS and OS. EGFR mutations were associated with upregulation of DPD and EGFR, and downregulation of TS and ERCC1. In conclusion, although pathological stage is an independent prognostic factor for survival, EGFR upregulation and TS downregulation may be a greater predictor of clinical outcomes in elderly patients with NSCLC treated with S?1 adjuvant chemotherapy. The age?related decrease in TS expression supports the potential benefit of 5?FU therapies in elderly patients. Nonetheless, further research is warranted to validate these results. en-copyright= kn-copyright= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkumuraNorihito en-aut-sei=Okumura en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiHiroyuki en-aut-sei=Suzuki en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakataMasao en-aut-sei=Nakata en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GembaKenicehi en-aut-sei=Gemba en-aut-mei=Kenicehi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SanoIsao en-aut-sei=Sano en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujinagaTakuji en-aut-sei=Fujinaga en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KataokaMasafumi en-aut-sei=Kataoka en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TerasakiYasuhiro en-aut-sei=Terasaki en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KataokaKazuhiko en-aut-sei=Kataoka en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KosakaShinji en-aut-sei=Kosaka en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=InokawaHidetoshi en-aut-sei=Inokawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= en-aut-name=NakamuraHiroshige en-aut-sei=Nakamura en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamashitaYoshinori en-aut-sei=Yamashita en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakahashiYuta en-aut-sei=Takahashi en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TorigoeHidejiro en-aut-sei=Torigoe en-aut-mei=Hidejiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 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=22 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=23 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=24 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=25 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=26 ORCID= en-aut-name=MatsuoKeitaro en-aut-sei=Matsuo en-aut-mei=Keitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=SakamotoJunichi en-aut-sei=Sakamoto en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=DateHiroshi en-aut-sei=Date en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 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=30 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Chest Surgery, Fukushima Medical University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Hiroshima 720?0001, Japan; 8Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, National Hospital Organization Nagara Medical Center kn-affil= affil-num=10 en-affil=Department of Surgery and Respiratory Center, Okayama Saiseikai General Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Surgery, Saga Medical Center Koseikan kn-affil= affil-num=12 en-affil=Department of Medical Oncology and Respiratory Medicine, Okayama Rosai Hospital kn-affil= affil-num=13 en-affil=Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=14 en-affil=Department of Thoracic Surgery, Shimane Prefectural Central Hospital kn-affil= affil-num=15 en-affil=Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=16 en-affil=Department of Thoracic Surgery, National Hospital Organization Yamaguchi?Ube Medical Center kn-affil= affil-num=17 en-affil=Department of Thoracic Surgery, Shimonoseki City Hospital kn-affil= affil-num=18 en-affil=Division of General Thoracic Surgery, Tottori University Hospital kn-affil= affil-num=19 en-affil=Department of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center kn-affil= affil-num=20 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=22 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=23 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=24 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=25 en-affil=Department of Thoracic Oncology, Kansai Medical University Hospital kn-affil= affil-num=26 en-affil=Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine kn-affil= affil-num=27 en-affil=Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute kn-affil= affil-num=28 en-affil=Tokai Central Hospital kn-affil= affil-num=29 en-affil=Department of Thoracic Surgery, Kyoto University Hospital kn-affil= affil-num=30 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=non?small cell lung cancer kn-keyword=non?small cell lung cancer en-keyword=elderly patients kn-keyword=elderly patients en-keyword=adjuvant chemotherapy kn-keyword=adjuvant chemotherapy en-keyword=S?1 kn-keyword=S?1 en-keyword=EGFR kn-keyword=EGFR en-keyword=TP kn-keyword=TP en-keyword=TS kn-keyword=TS en-keyword=OPRT kn-keyword=OPRT en-keyword=ERCC1 kn-keyword=ERCC1 en-keyword=DPD kn-keyword=DPD END start-ver=1.4 cd-journal=joma no-vol=120 cd-vols= no-issue=1 article-no= start-page=87 end-page=98 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparable Clinical Outcomes Between Segmentectomy and Lobectomy for NSCLC With Unsuspected N1/N2: A Multicenter Real-World Data Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Segmentectomy for lung cancer has been increasingly performed. However, evidence regarding the necessity of additional surgical resection after the diagnosis of unsuspected N1 or N2 lymph node metastasis is limited.
Methods We conducted a multicenter, real-world data study of patients with any clinical T and N0 non-small cell lung cancer (NSCLC) who underwent lobectomy or segmentectomy between 2012 and 2021 and who subsequently received a diagnosis of pathologic N1 or N2 lymph node metastasis. Patients were categorized into lobectomy and segmentectomy groups. We analyzed overall survival (OS), recurrence-free survival (RFS), cumulative recurrence rates, and recurrence patterns using both unadjusted and propensity score?adjusted cohorts.
Results A total of 736 patients were in the lobectomy group, and 70 were in the segmentectomy group. In the unadjusted cohort, segmentectomy-treated patients were older, had a lower preoperative percentage of vital capacity, had smaller tumors, and received less postoperative adjuvant chemotherapy. The 5-year OS was significantly worse in the segmentectomy group (P = .011), with no significant differences in 5-year RFS or cumulative recurrence rates. In the propensity score?adjusted cohort, there were no significant differences in OS, RFS, or recurrence rates; however, the segmentectomy group had a higher rate of local recurrence.
Conclusions In patients with unsuspected N1 or N2 NSCLC, analysis using a cohort adjusted for patient background with propensity scores revealed no differences in OS, RFS, or cumulative recurrence rates between segmentectomy and lobectomy. This finding suggests that additional resection of the remaining segments may not be necessary for these patients. However, the higher rate of local recurrence in the segmentectomy group warrants careful consideration. en-copyright= kn-copyright= en-aut-name=RyukoTsuyoshi en-aut-sei=Ryuko en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UenoTsuyoshi en-aut-sei=Ueno en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeMototsugu en-aut-sei=Watanabe en-aut-mei=Mototsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=InokawaHidetoshi en-aut-sei=Inokawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MisaoTakahiko en-aut-sei=Misao en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TorigoeHidejiro en-aut-sei=Torigoe en-aut-mei=Hidejiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WashioKazuhiro en-aut-sei=Washio en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TaoHiroyuki en-aut-sei=Tao en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OkutaniDaisuke en-aut-sei=Okutani en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HayamaMakio en-aut-sei=Hayama en-aut-mei=Makio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=UomotoMasashi en-aut-sei=Uomoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamadaEiji en-aut-sei=Yamada en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OtaniShinji en-aut-sei=Otani en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KurosakiTakeshi en-aut-sei=Kurosaki en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YaginumaYuji en-aut-sei=Yaginuma en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NimanEito en-aut-sei=Niman en-aut-mei=Eito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KawamataOsamu en-aut-sei=Kawamata en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=NishikawaHitoshi en-aut-sei=Nishikawa en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OtsukaTomoaki en-aut-sei=Otsuka en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YoshikawaTakeshi en-aut-sei=Yoshikawa en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=HayashiTatsuro en-aut-sei=Hayashi en-aut-mei=Tatsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 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=27 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=7 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=8 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=9 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=10 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=11 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=12 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=13 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=14 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=15 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=16 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=17 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=18 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=19 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=20 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=21 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=22 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=23 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=24 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=25 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=26 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=27 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=10 article-no= start-page=1215 end-page=1227 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=Enhanced design of pCMViR-TSC plasmid vector for sustainably high cargo gene expression in mammalian cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=The first-generation pCMViR-TSC, implemented through the promoter sandwich rule, yields 10- to 100-fold higher gene expression than the standard plasmid used with the CMV (cytomegalovirus) or CAG promoter. However, the vector’s shortcomings limit its utility to transient expression only, as it is not suitable for establishing stable transformants in mammalian cells. To overcome this weakness, we here introduce the improved plasmid vector pSAKA-4B, derived from pCMViR-TSC as a second-generation chromosome-insertable vector. This vector facilitates the linear entry of the expression unit into the TTAA site of DNA universally with transposase assistance. The vector is helpful for the indefinite expression of our target gene. The new vector system is proven here to be efficient in establishing stable transformants with a high likelihood of positive clones that exhibit significantly elevated expression levels of the delivered foreign gene. This system, alongside the first-generation vector, is therefore instrumental for diverse basic research endeavors concerning genes, proteins, cells, and animals, and potentially for clinical applications such as gene therapy. en-copyright= kn-copyright= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakaguchiYoshihiko en-aut-sei=Sakaguchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=YamauchiAkira en-aut-sei=Yamauchi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MurataHitoshi en-aut-sei=Murata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoKen-ichi en-aut-sei=Yamamoto en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakahashiTetta en-aut-sei=Takahashi en-aut-mei=Tetta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GoharaYuma en-aut-sei=Gohara en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OchiToshiki en-aut-sei=Ochi en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=JiangFan en-aut-sei=Jiang en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KomalasariNi Luh Gede Yoni en-aut-sei=Komalasari en-aut-mei=Ni Luh Gede Yoni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ChenYouyi en-aut-sei=Chen en-aut-mei=Youyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=RumaI Made Winarsa en-aut-sei=Ruma en-aut-mei=I Made Winarsa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SumardikaI Wayan en-aut-sei=Sumardika en-aut-mei=I Wayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ZhouJin en-aut-sei=Zhou en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 ORCID= en-aut-name=KuribayashiFutoshi en-aut-sei=Kuribayashi en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SagayamaKazumi en-aut-sei=Sagayama en-aut-mei=Kazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 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=21 ORCID= en-aut-name=KondoEisaku en-aut-sei=Kondo en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=InoueYusuke en-aut-sei=Inoue en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Microbiology, Tokushima Bunri University kn-affil= affil-num=5 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=14 en-affil=Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=15 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=16 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=17 en-affil=Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology kn-affil= affil-num=18 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=19 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=20 en-affil=Organization for Research and Innovation Strategy, Okayama University kn-affil= affil-num=21 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=22 en-affil=Division of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical University kn-affil= affil-num=23 en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= en-keyword=Plasmid kn-keyword=Plasmid en-keyword=Gene engineering kn-keyword=Gene engineering en-keyword=Cancer kn-keyword=Cancer en-keyword=Cell culture kn-keyword=Cell culture 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=2025 dt-pub=20250718 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Advances in liquid biopsy for bone and soft-tissue sarcomas en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bone and soft-tissue sarcomas are a heterogeneous group of malignant tumors originating from mesenchymal tissues, accounting for approximately 1% of adult solid malignancies and 20% of pediatric solid malignancies. While blood-based tumor markers are available in major types of cancers, evidence demonstrating useful circulating biomarkers is limited in bone and soft-tissue sarcomas. Despite the development of combined modality treatments, a significant proportion of sarcoma patients respond poorly to chemotherapy or radiotherapy, leading to local relapse or distant metastasis. However, imaging methods, such as X-ray, computed tomography, positron emission tomography, magnetic resonance imaging, and scintigraphy, are mostly used to detect or monitor tumor development. Liquid biopsy is an emerging minimally invasive diagnostic technique that detects tumor-derived molecules in body fluids, including circulating tumor cells, circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA), and circulating extracellular vesicles. This method offers new possibilities for early tumor detection, prognostic evaluation, and therapeutic monitoring and may serve as a benchmark for treatment modification. This review focuses on the current technological advances in liquid biopsy for bone and soft-tissue sarcoma and explores its potential role in guiding personalized treatments. If these modalities could determine resistance to ongoing therapy or the presence of minimal residual disease at the end of the treatment protocol, the obtained data would be important for determining whether to change treatment approaches or add adjuvant therapies. en-copyright= kn-copyright= en-aut-name=WangYilang en-aut-sei=Wang en-aut-mei=Yilang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurozumiTakanao en-aut-sei=Kurozumi en-aut-mei=Takanao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AndoTeruhiko en-aut-sei=Ando en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshimaruTakahiko en-aut-sei=Ishimaru en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KondoHiroya en-aut-sei=Kondo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, 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= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Liquid biopsy kn-keyword=Liquid biopsy en-keyword=Bone sarcoma kn-keyword=Bone sarcoma en-keyword=Soft-tissue sarcoma kn-keyword=Soft-tissue sarcoma en-keyword=Circulating tumor cells kn-keyword=Circulating tumor cells en-keyword=Circulating nucleic acids kn-keyword=Circulating nucleic acids en-keyword=Circulating microvesicles kn-keyword=Circulating microvesicles END start-ver=1.4 cd-journal=joma no-vol=86 cd-vols= no-issue= article-no= start-page=103389 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Global trends in mortality related to pulmonary embolism: an epidemiological analysis of data from the World Health Organization mortality database from 2001 to 2023 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaradaKo en-aut-sei=Harada en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoMaki en-aut-sei=Yamamoto en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimuraSayoko en-aut-sei=Nishimura en-aut-mei=Sayoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoMichio en-aut-sei=Yamamoto en-aut-mei=Michio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NiimuraTakahiro en-aut-sei=Niimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OsakiYuka en-aut-sei=Osaki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=FujiiMariko en-aut-sei=Fujii en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakoNanami en-aut-sei=Sako en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 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=14 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=15 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=2 en-affil=Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=3 en-affil=Division of Hematology and Oncology, Mayo Clinic kn-affil= affil-num=4 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Human Sciences, Osaka University kn-affil= affil-num=7 en-affil=Department of Clinical Pharmacology and Therapeutics, Institute of Biomedical Sciences, Tokushima University Graduate School kn-affil= affil-num=8 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Center for Education in Medicine and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Pharmacy, Medical Development Field, Okayama University kn-affil= affil-num=14 en-affil=Department of Pharmacy, Medical Development Field, Okayama University kn-affil= affil-num=15 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Pulmonary embolism kn-keyword=Pulmonary embolism en-keyword=Mortality kn-keyword=Mortality en-keyword=WHO kn-keyword=WHO en-keyword=Global trends kn-keyword=Global trends END start-ver=1.4 cd-journal=joma no-vol=150 cd-vols= no-issue=1 article-no= start-page=19 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biallelic variants in DNAJC7 cause familial amyotrophic lateral sclerosis with the TDP-43 pathology en-subtitle= kn-subtitle= en-abstract= kn-abstract=Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. ALS pathology primarily involves the failure of protein quality control mechanisms, leading to the accumulation of misfolded proteins, particularly TAR DNA-binding protein 43 (TDP-43). TDP-43 aggregation is a central pathological feature of ALS. Maintaining protein homeostasis is critical and facilitated by heat shock proteins (HSPs), particularly the HSP40 family, which includes co-chaperones such as DNAJC7. Here, we report a family with three siblings affected by ALS who carry a homozygous c.518dupC frameshift variant in DNAJC7, a member of the HSP40 family. All three patients exhibited progressive muscle weakness, limb atrophy, bulbar palsy, and respiratory failure. Pathological examination revealed degeneration of both upper and lower motor neurons, with phosphorylated TDP-43-positive neuronal cytoplasmic inclusions in the frontal and temporal cortices. Immunoblot analysis were consistent with a type B pattern of phosphorylated TDP-43 in the precentral gyrus. Immunohistochemistry and RNA sequencing analyses demonstrated a substantial reduction in DNAJC7 expression at both the protein and RNA levels in affected brain regions. In a TDP-43 cell model, DNAJC7 knockdown impaired the disassembly of TDP-43 following arsenite-induced stress, whereas DNAJC7 overexpression suppressed the assembly and promoted the disassembly of arsenite-induced TDP-43 condensates. Furthermore, in a zebrafish ALS model, dnajc7 knockdown resulted in increased TDP-43 aggregation in motor neurons and reduced survival. To the best of our knowledge, this study provides the first evidence linking biallelic loss-of-function variants in DNAJC7 to familial ALS with TDP-43 pathology. en-copyright= kn-copyright= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokotaOsamu en-aut-sei=Yokota en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OusakaDaiki en-aut-sei=Ousaka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SunHongming en-aut-sei=Sun en-aut-mei=Hongming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiTakashi en-aut-sei=Haraguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Ota-ElliottRicardo Satoshi en-aut-sei=Ota-Elliott en-aut-mei=Ricardo Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuokaChika en-aut-sei=Matsuoka en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawanoTomohito en-aut-sei=Kawano en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Nakashima-YasudaHanae en-aut-sei=Nakashima-Yasuda en-aut-mei=Hanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukuiYusuke en-aut-sei=Fukui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakanoYumiko en-aut-sei=Nakano en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=HosonoYasuyuki en-aut-sei=Hosono en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TeradaSeishi en-aut-sei=Terada en-aut-mei=Seishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurology, National Hospital Organisation Minami-Okayama Medical Centre kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Psychiatry, Zikei Hospital kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Brain and Neurosciences, Tokyo Metropolitan Institute of Medical Science kn-affil= affil-num=14 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Amyotrophic lateral sclerosis kn-keyword=Amyotrophic lateral sclerosis en-keyword=Heat shock protein kn-keyword=Heat shock protein en-keyword=DNAJC7 kn-keyword=DNAJC7 en-keyword=TDP-43 kn-keyword=TDP-43 en-keyword=Live-cell imaging kn-keyword=Live-cell imaging en-keyword=Zebrafish disease model kn-keyword=Zebrafish disease model END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=27502 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Autoantibody spark response predicts treatment outcome in patients receiving chemoradiation followed by durvalumab therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=The PACIFIC regimen, comprising chemoradiotherapy (CRT) followed by maintenance with the immune checkpoint inhibitor (ICI) durvalumab, has become the standard of care for patients with unresectable non-small cell lung cancer (NSCLC). Although ICI is used to prevent recurrence by targeting residual microtumors, biomarkers capable of monitoring immune activity during this phase remain lacking. Here, we evaluated whether temporal changes in serum autoantibody levels can predict treatment efficacy. This retrospective study included 20 patients with unresectable stage II or III NSCLC who received the PACIFIC regimen. Serum autoantibodies against 130 antigens were quantified before CRT, after CRT, and two weeks after the first ICI dose. The primary outcome was progression-free survival (PFS), and its association with autoantibody dynamics was examined. We observed an immediate and strong autoantibody response (spark response [SR]) after ICI initiation in patients with favorable treatment outcomes. Patients with SR and programmed death ligand 1 (PD-L1) expression???50% showed better PFS (two-year PFS; 72.9% vs. 18.2%, p?=?0.0021). These findings suggest that serial monitoring of serum autoantibodies can provide a noninvasive approach to assess immune activity and predict treatment outcomes in patients receiving CRT or ICI therapy. en-copyright= kn-copyright= en-aut-name=MoriTakeru en-aut-sei=Mori en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitagawaMio en-aut-sei=Kitagawa en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasegawaTomokazu en-aut-sei=Hasegawa en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SomeyaMasanori en-aut-sei=Someya en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuchiyaTakaaki en-aut-sei=Tsuchiya en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GochoToshio en-aut-sei=Gocho en-aut-mei=Toshio 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=DateMirei en-aut-sei=Date en-aut-mei=Mirei 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=MiyamotoAi en-aut-sei=Miyamoto en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=Department of Radiology, Sapporo Medical University School of Medicine kn-affil= affil-num=3 en-affil=Department of Radiology, Sapporo Medical University School of Medicine kn-affil= affil-num=4 en-affil=Department of Radiology, Sapporo Medical University School of Medicine kn-affil= affil-num=5 en-affil=Department of Radiology, Sapporo Medical University School of Medicine kn-affil= affil-num=6 en-affil=Department of Radiology, Sapporo Medical University School of Medicine 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=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University 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=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=Autoantibodies kn-keyword=Autoantibodies en-keyword=PACIFIC regimen kn-keyword=PACIFIC regimen en-keyword=ICIs kn-keyword=ICIs en-keyword=Immune monitoring kn-keyword=Immune monitoring END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=6 article-no= start-page=e00110-25 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mycobacterium tuberculosis bacillus induces pyroptosis in human lung fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=We previously reported that live, but not dead, virulent Mycobacterium tuberculosis (Mtb) H37Rv bacilli induce cell death in human lung fibroblast cell lines, MRC-5, MRC-9, and TIG-1. Here, using two distinct Mtb strains from two different lineages (HN878 lineage 2 and H37Rv lineage 4), we confirmed cell death at day 2 after infection with a device that measures cell growth/cytotoxicity in real time (Maestro-Z [AXION]). Mtb bacilli uptake by the fibroblast was confirmed with a transmission electron microscope on day 2. Expressions of inflammatory cytokines and interleukin (IL)?1β, IL-6, and IL-8 were observed when exposed to live, but not dead bacteria. The cell death of fibroblasts induced by both Mtb strains tested was prevented by caspase-1/4 and NLRP3 inflammasome inhibitors, but not by caspase-3 and caspase-9 inhibitors. Therefore, we classified the fibroblast cell death by Mtb infection as pyroptosis. To investigate the biological and pathological relevance of fibroblast cell death by Mtb infection, we performed dual RNA-Seq analysis on Mtb within fibroblasts and Mtb-infected fibroblasts at day 2. In Mtb bacilli tcrR, secE2, ahpD, and mazF8 genes were highly induced during infection. These genes play roles in survival in a hypoxic environment, production of a calcium-binding protein-inducing cytokine, and regulation of transcription in a toxin-antitoxin system. The gene expressions of IL-1β, IL-6, and IL-8, caspase-4, and NLRP3, but not of caspase-3 and caspase-9, were augmented in Mtb bacilli-infected fibroblasts. Taken together, our study suggests that Mtb bacilli attempt to survive in lung fibroblasts and that pyroptosis of the host fibroblasts activates the immune system against the infection. 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=YamadaHiroyuki en-aut-sei=Yamada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotozonoChihiro en-aut-sei=Motozono en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamasakiSho en-aut-sei=Yamasaki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TorrellesJordi B. en-aut-sei=Torrelles en-aut-mei=Jordi B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TurnerJoanne en-aut-sei=Turner en-aut-mei=Joanne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HidaShigeaki en-aut-sei=Hida en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=OnozakiKikuo en-aut-sei=Onozaki en-aut-mei=Kikuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=3 en-affil=Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka kn-affil= affil-num=4 en-affil=Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka kn-affil= affil-num=5 en-affil=Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I?CARE) kn-affil= affil-num=6 en-affil=Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I?CARE) kn-affil= affil-num=7 en-affil=Laboratory of Applied Microbial Chemistry, ?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=8 en-affil=Laboratory of Applied Microbial Chemistry, ?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=9 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=11 en-affil=Department of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=12 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= en-keyword=Mycobacterium tuberculosis kn-keyword=Mycobacterium tuberculosis en-keyword=pyroptosis kn-keyword=pyroptosis en-keyword=caspase kn-keyword=caspase en-keyword=RNA-Seq kn-keyword=RNA-Seq en-keyword=cytokine kn-keyword=cytokine en-keyword=fibroblasts kn-keyword=fibroblasts 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=2025 dt-pub=20250811 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Study of the Mechanical Properties of Al?Mg ADC6 Aluminum Alloy Produced by Unidirectional Casting Under Various Cooling Rates en-subtitle= kn-subtitle= en-abstract= kn-abstract=To create the high strength and high ductility of Al?Mg-based aluminum alloy (JIS?ADC6), ADC6 samples were produced by the unidirectional continuous casting (HMC). The HMC process was conducted with direct water cooling to melt ADC6, which can make fine microstructures and control crystal orientation. The cast samples were prepared under various cooling rates (CRs): 6.3, 34, and 62 K/s. The microstructure and crystal orientation of the samples were altered with CR. At CRs of 34 K/s and 62 K/s, the α-Al phases and intermetallic compounds, e.g., Mg2Si and Al15(Fe, Mn)3Si2, became finer and more spherical. The secondary dendrite arm spacing for the sample at 62 K/s was 8.7 ?m?more than 70% smaller than the ADC6 sample (ingot) made by a gravity casting process. Notably, at a CR of 34 K/s, the crystal orientation was predominantly arranged with the (101) plane. Tensile properties?ultimate tensile strength (σUTS), 0.2% proof stress (σ0.2), and failure strain (εf)?varied with the CR. The tensile strength (σUTS and σ0.2) consistently increased with increasing the CR. The improvement in the tensile strength resulted from the refined microstructures, such as the α-Al phase and intermetallic compounds. Similarly, the failure strain also increased with increasing CR, which was severely affected by the finer and more spherical intermetallic compounds. In this case, the εf value of the sample at 34 K/s was, however, slightly higher than that at 62 K/s, due to more uniformly organized crystal orientation, while their ductility was much higher than that of the gravity cast sample. The tensile properties in detail were further analyzed using their failure characteristics. en-copyright= kn-copyright= en-aut-name=TakeuchiS. en-aut-sei=Takeuchi en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkayasuM. en-aut-sei=Okayasu en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= en-keyword=Al-Mg alloy kn-keyword=Al-Mg 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=crystal orientation kn-keyword=crystal orientation en-keyword=fractography kn-keyword=fractography END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=11 article-no= start-page=348 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Coronal Cementum and Reduced Enamel Epithelium on Occlusal Surface of Impacted Wisdom Tooth in a Human en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: There is only limited research on the coronal cementum of a tooth, and the mechanisms of its forming process are not well-defined. This report presents a coronal cementum on the occlusal surfaces of enamel in an impacted wisdom tooth in a human, which is not nearly the cervical portion. Materials and Methods: The tooth (Tooth #1) was derived from a 46-year-old female. Histological analysis, including hematoxylin and eosin (HE) and toluidine blue (TB) staining, and Scanning Electron Microscopy and Energy Dispersive X-ray Spectrometer (SEM-EDS) analysis of the extracted tooth were conducted. Radiographic examination showed that Tooth #1 was horizontally impacted in the maxilla and had the apex of a single root placed between the buccal and palatal roots of Tooth #2. Results: Coronal cementum was distributed widely on the enamel, and reduced enamel epithelium was also found with enamel matrix proteins histologically. The formation of acellular cementum was observed to be more predominant than that of the cellular cementum in Tooth #1. SEM showed that the occlusal cementum connected directly with enamel. Calcium mapping revealed an almost similar occlusal cementum and enamel. In addition, the spectrum of elements in coronal cementum resembled the primary cementum according to SEM-EDS. Discussion: Thus, coronal cementogenesis in impacted human teeth might be related to the existence of reduced enamel epithelium. en-copyright= kn-copyright= en-aut-name=HorieNaohiro en-aut-sei=Horie en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MurataMasaru en-aut-sei=Murata en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MinamidaYasuhito en-aut-sei=Minamida en-aut-mei=Yasuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagayasuHiroki en-aut-sei=Nagayasu en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=AkazawaToshiyuki en-aut-sei=Akazawa en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujigiwaHidetsugu en-aut-sei=Tsujigiwa en-aut-mei=Hidetsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaikelYoussef en-aut-sei=Haikel en-aut-mei=Youssef 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= affil-num=1 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=2 en-affil=Division of Regenerative Medicine, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=3 en-affil=Division of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=4 en-affil=Division of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=5 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=6 en-affil=Industrial Technology and Environment Research Development, Hokkaido Research Organization kn-affil= affil-num=7 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= affil-num=8 en-affil=Department of Biomaterials and Bioengineering, Institut National de la Sant? et de la Recherche m?dicale Unit? Mixte de Recherche (INSERM UMR) _S 1121, University of Strasbourg kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=coronal cementum kn-keyword=coronal cementum en-keyword=human kn-keyword=human en-keyword=reduced epithelium kn-keyword=reduced epithelium en-keyword=impacted tooth kn-keyword=impacted tooth END start-ver=1.4 cd-journal=joma no-vol=156 cd-vols= no-issue= article-no= start-page=107913 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recurrent diffuse panbronchiolitis after lung transplantation: Off-label use of inhaled tobramycin for Pseudomonas aeruginosa control in a transplant recipient en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: This report highlights a clinical case of recurrent diffuse panbronchiolitis (DPB) after bilateral lung transplantation (LTx), with a focus on the therapeutic impact of off-label inhaled tobramycin solution for inhalation (TSI) in managing Pseudomonas aeruginosa colonization.
Methods: A Japanese woman with a history of DPB experienced disease recurrence following bilateral LTx. Persistent colonization by P. aeruginosa and recurrent respiratory symptoms were observed. Off-label TSI therapy, commonly used in cystic fibrosis, was introduced. Clinical response was assessed through radiologic imaging, bronchoscopy, and microbiological cultures.
Results: TSI administration led to significant clinical and radiological improvement. P. aeruginosa was eradicated from sputum cultures within one month and remained absent throughout six months of follow-up. No hospitalizations or adverse events were reported during therapy.
Conclusion: This case suggests the potential of TSI as a therapeutic approach for managing recurrent DPB and indicates its role in stabilizing post-transplant outcomes. Further studies may clarify its efficacy and expand its application in broader DPB management strategies. en-copyright= kn-copyright= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RyukoTuyoshi en-aut-sei=Ryuko en-aut-mei=Tuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Inhaled tobramycin kn-keyword=Inhaled tobramycin en-keyword=Lung transplantation kn-keyword=Lung transplantation en-keyword=Pseudomonas aeruginosa kn-keyword=Pseudomonas aeruginosa en-keyword=Recurrent diffuse panbronchiolitis kn-keyword=Recurrent diffuse panbronchiolitis END start-ver=1.4 cd-journal=joma no-vol=779 cd-vols= no-issue= article-no= start-page=152453 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250912 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=1,2-naphthoquinone enhances IFN-γ-induced MHC-I expression in dendritic cells, thereby inducing CD8 T cell activation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dendritic cells play a crucial role in immune responses by capturing pathogens and presenting antigens to T cells via major histocompatibility complex (MHC) molecules, thus triggering adaptive immune responses. 1,2-naphthoquinone (1,2-NQ), a quinone found in diesel exhaust and cigarette smoke, has various physiological functions. In this study, we investigated the effect of 1,2-NQ on the expression of antigen presentation-related molecules in the dendritic cell line DC2.4. The results revealed that 1,2-NQ enhanced the IFN-γ-induced upregulation of MHC-I expression at the transcriptional level. Moreover, it upregulated the expression of NLRC5, a transcriptional activator of MHC-I. 1,2-NQ is a reactive oxygen species (ROS) producing reagent. The 1,2-NQ-induced upregulation of MHC-I expression and downregulation of MHC-II expression were abolished by the ROS scavenger N-acetylcysteine. Similar effects on MHC expression were also observed with ROS-inducing reagents, such as paraquat and diethyl maleate. In addition, dendritic cells stimulated with 1,2-NQ exhibited enhanced efficacy in CD8 T cell activation, which was accompanied by increased IFN-γ production by T cells. These findings demonstrate that 1,2-NQ enhances the IFN-γ-induced activation of dendritic cells and promotes the activation of CD8 T cells. en-copyright= kn-copyright= en-aut-name=FurutaKazuyuki en-aut-sei=Furuta en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazatoKanon en-aut-sei=Miyazato en-aut-mei=Kanon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobataKai en-aut-sei=Kobata en-aut-mei=Kai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=KaitoChikara en-aut-sei=Kaito en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=1,2-Napthoquinone kn-keyword=1,2-Napthoquinone en-keyword=Dendritic cell kn-keyword=Dendritic cell en-keyword=IFN-γ kn-keyword=IFN-γ en-keyword=MHC-I kn-keyword=MHC-I en-keyword=CD8 T cell kn-keyword=CD8 T cell END start-ver=1.4 cd-journal=joma no-vol=122 cd-vols= no-issue=32 article-no= start-page=e2501933122 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250805 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural insights into a citrate transporter that mediates aluminum tolerance in barley en-subtitle= kn-subtitle= en-abstract= kn-abstract=HvAACT1 is a major aluminum (Al)-tolerance gene in barley, encoding a citrate transporter that belongs to the multidrug and toxic compound extrusion (MATE) family. This transporter facilitates citrate secretion from the roots, thereby detoxifying external Al ions?a major constraint of crop production on acidic soils. In this study, we present the outward-facing crystal structure of HvAACT1, providing insights into a citrate transport mechanism. The putative citrate binding site consists of three basic residues?K126 in transmembrane helix 2 (TM2), R358 in TM7, and R535 in TM12?creating substantial positive charges in the C-lobe cavity. Proton coupling for substrate transport may involve two pairs of aspartate residues in the N-lobe cavity, one of which corresponds to the essential Asp pair found in prokaryotic H+-coupled MATE transporters belonging to the DinF subfamily. Structural coupling between proton uptake in the N-lobe and citrate extrusion in the C-lobe can be enabled by an extensive, unique hydrogen-bonding network at the extracellular half of the N-lobe. Mutation-based functional analysis, structural comparisons, molecular dynamics simulation, and phylogenic analysis suggest an evolutionary link between citrate MATE transporters and the DinF MATE subfamily. Our findings provide a solid structural basis for citrate transport by HvAACT1 in barley and contribute to a broader understanding of citrate transporter structures in other plant species. en-copyright= kn-copyright= en-aut-name=Nguyen ThaoTran en-aut-sei=Nguyen Thao en-aut-mei=Tran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Mitani-UenoNamiki en-aut-sei=Mitani-Ueno en-aut-mei=Namiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UranoRyo en-aut-sei=Urano en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitohYasunori en-aut-sei=Saitoh en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangPeitong en-aut-sei=Wang en-aut-mei=Peitong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamajiNaoki en-aut-sei=Yamaji en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShinodaWataru en-aut-sei=Shinoda en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=SugaMichihiro en-aut-sei=Suga en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Division of Superconducting and Functional Materials, Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=5 en-affil=Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=8 en-affil=Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=9 en-affil=Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=10 en-affil=Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= en-keyword=barley kn-keyword=barley en-keyword=aluminum resistance kn-keyword=aluminum resistance en-keyword=membrane protein structure kn-keyword=membrane protein structure en-keyword=citrate transporter kn-keyword=citrate transporter en-keyword=MATE transporter kn-keyword=MATE transporter END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=8 article-no= start-page=3474 end-page=3475 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250806 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gene replacement therapy for centronuclear myopathy: A breakthrough in complex genetic muscle disease en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TakedaTetsuya en-aut-sei=Takeda en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=154 cd-vols= no-issue= article-no= start-page=107863 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Secondary pneumothorax due to Aspergillus welwitschiae in a lung transplant recipient en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=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=BanSayaka en-aut-sei=Ban en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YaguchiTakashi en-aut-sei=Yaguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeAkira en-aut-sei=Watanabe en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Medical Mycology Research Center, Chiba University kn-affil= affil-num=4 en-affil=Medical Mycology Research Center, Chiba University kn-affil= affil-num=5 en-affil=Medical Mycology Research Center, Chiba University kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= en-keyword=Aspergillus section Nigri kn-keyword=Aspergillus section Nigri en-keyword=Aspergillus tracheobronchitis kn-keyword=Aspergillus tracheobronchitis en-keyword=Invasive pulmonary aspergillosis kn-keyword=Invasive pulmonary aspergillosis en-keyword=Pneumothorax kn-keyword=Pneumothorax END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=8 article-no= start-page=522 end-page=532 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240625 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis and biochemical characterization of naphthoquinone derivatives targeting bacterial histidine kinases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Waldiomycin is an inhibitor of histidine kinases (HKs). Although most HK inhibitors target the ATP-binding region, waldiomycin binds to the intracellular dimerization domain (DHp domain) with its naphthoquinone moiety presumed to interact with the conserved H-box region. To further develop inhibitors targeting the H-box, various 2-aminonaphthoquinones with cyclic, aliphatic, or aromatic amino groups and naphtho [2,3-d] isoxazole-4,9-diones were synthesized. These compounds were tested for their inhibitory activity (IC50) against WalK, an essential HK for Bacillus subtilis growth, and their minimum inhibitory concentrations (MIC) against B. subtilis. As a result, 11 novel HK inhibitors were obtained as naphthoquinone derivatives (IC50: 12.6?305??M, MIC: 0.5?128??g?ml?1). The effect of representative compounds on the expression of WalK/WalR regulated genes in B. subtilis was investigated. Four naphthoquinone derivatives induced the expression of iseA (formerly yoeB), whose expression is negatively regulated by the WalK/WalR system. This suggests that these compounds inhibit WalK in B. subtilis cells, resulting in antibacterial activity. Affinity selection/mass spectrometry analysis was performed to identify whether these naphthoquinone derivatives interact with WalK in a manner similar to waldiomycin. Three compounds were found to competitively inhibit the binding of waldiomycin to WalK, suggesting that they bind to the H-box region conserved in HKs and inhibit HK activity. en-copyright= kn-copyright= en-aut-name=IshikawaTeruhiko en-aut-sei=Ishikawa en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EguchiYoko en-aut-sei=Eguchi en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IgarashiMasayuki en-aut-sei=Igarashi en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkajimaToshihide en-aut-sei=Okajima en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MitaKohei en-aut-sei=Mita en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamasakiYuri en-aut-sei=Yamasaki en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SumikuraKaho en-aut-sei=Sumikura en-aut-mei=Kaho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkumuraTaisei en-aut-sei=Okumura en-aut-mei=Taisei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TabuchiYuna en-aut-sei=Tabuchi en-aut-mei=Yuna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HayashiChigusa en-aut-sei=Hayashi en-aut-mei=Chigusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=PasquaMartina en-aut-sei=Pasqua en-aut-mei=Martina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ColucciaMarco en-aut-sei=Coluccia en-aut-mei=Marco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ProssedaGianni en-aut-sei=Prosseda en-aut-mei=Gianni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ColonnaBianca en-aut-sei=Colonna en-aut-mei=Bianca kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KohayakawaChie en-aut-sei=Kohayakawa en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TaniAkiyoshi en-aut-sei=Tani en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HarutaJun-ichi en-aut-sei=Haruta en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UtsumiRyutaro en-aut-sei=Utsumi en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=2 en-affil=Department of Science and Technology on Food Safety, Faculty of Biology-Oriented Science and Technology, Kindai University kn-affil= affil-num=3 en-affil=Institute of Microbial Chemistry (BIKAKEN) kn-affil= affil-num=4 en-affil=SANKEN (The Institute of Scientific and Industrial Research), Osaka University kn-affil= affil-num=5 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=10 en-affil=Institute of Microbial Chemistry (BIKAKEN) kn-affil= affil-num=11 en-affil=Istituto Pasteur Italy, Department of Biology and Biotechnology, “C. Darwin”, Sapienza University of Rome kn-affil= affil-num=12 en-affil=Istituto Pasteur Italy, Department of Biology and Biotechnology, “C. Darwin”, Sapienza University of Rome kn-affil= affil-num=13 en-affil=Istituto Pasteur Italy, Department of Biology and Biotechnology, “C. Darwin”, Sapienza University of Rome kn-affil= affil-num=14 en-affil=Istituto Pasteur Italy, Department of Biology and Biotechnology, “C. Darwin”, Sapienza University of Rome kn-affil= affil-num=15 en-affil=Department of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, Osaka University kn-affil= affil-num=16 en-affil=Compound Library Screening Center, Graduate School of Pharmaceutical Sciences, Osaka University kn-affil= affil-num=17 en-affil=Department of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, Osaka University kn-affil= affil-num=18 en-affil=SANKEN (The Institute of Scientific and Industrial Research), Osaka University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=1 end-page=11 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250707 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dual roles of suberin deposition at the endodermal Casparian strip in manganese uptake of rice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rice roots are characterized by having two Casparian strips (CSs) at the exodermis and endodermis, where transporters for mineral nutrients are expressed. However, the exact role of the CS in expression of the transporters and subsequent nutrient uptake is poorly understood. Here, we first investigated the role of the CS in manganese (Mn) uptake by using a rice mutant (oscasp1) defective in formation of the endodermal CS. Knockout of OsCASP1 resulted in decreased Mn uptake under limited Mn conditions, but increased Mn uptake at high Mn concentration. Immunostaining revealed that knockout of OsCASP1 did not affect the cell specificity of localization of two transporters (OsNramp5 and OsMTP9) required for Mn uptake, but decreased the protein abundance of these transporters at the endodermis regardless of Mn concentrations tested. Furthermore, we found that overaccumulation of suberin at the endodermis of the mutants suppressed the expression of two transporters; the expression of the two transporters was only observed in the endodermal cells without suberin deposition, but not in the cells with suberin deposition. Taken together, our results indicate that there are two roles for the CS in Mn uptake; maintaining normal expression of the transporters at limited Mn concentration and preventing Mn diffusion to the stele at high Mn concentration. en-copyright= kn-copyright= en-aut-name=FujiiToshiki en-aut-sei=Fujii en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamajiNaoki en-aut-sei=Yamaji en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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= en-keyword=Casparian strip kn-keyword=Casparian strip en-keyword=endodermis kn-keyword=endodermis en-keyword=manganese transporter kn-keyword=manganese transporter en-keyword=rice kn-keyword=rice en-keyword=root kn-keyword=root en-keyword=suberin deposition kn-keyword=suberin deposition END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=3 article-no= start-page=99 end-page=117 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240429 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Generation and characterization of cerebellar granule neurons specific knockout mice of Golli-MBP en-subtitle= kn-subtitle= en-abstract= kn-abstract=Golli?myelin basic proteins, encoded by the myelin basic protein gene, are widely expressed in neurons and oligodendrocytes in the central nervous system. Further, prior research has shown that Golli?myelin basic protein is necessary for myelination and neuronal maturation during central nervous system development. In this study, we established Golli?myelin basic protein-floxed mice to elucidate the cell-type-specific effects of Golli?myelin basic protein knockout through the generation of conditional knockout mice (Golli?myelin basic proteinsfl/fl; E3CreN), in which Golli?myelin basic proteins were specifically deleted in cerebellar granule neurons, where Golli?myelin basic proteins are expressed abundantly in wild-type mice. To investigate the role of Golli?myelin basic proteins in cerebellar granule neurons, we further performed histopathological analyses of these mice, with results indicating no morphological changes or degeneration of the major cellular components of the cerebellum. Furthermore, behavioral analysis showed that Golli?myelin basic proteinsfl/fl; E3CreN mice were healthy and did not display any abnormal behavior. These results suggest that the loss of Golli?myelin basic proteins in cerebellar granule neurons does not lead to cerebellar perturbations or behavioral abnormalities. This mouse model could therefore be employed to analyze the effect of Golli?myelin basic protein deletion in specific cell types of the central nervous system, such as other neuronal cells and oligodendrocytes, or in lymphocytes of the immune system. en-copyright= kn-copyright= en-aut-name=MiyazakiHaruko en-aut-sei=Miyazaki en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiokaSaki en-aut-sei=Nishioka en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamanakaTomoyuki en-aut-sei=Yamanaka en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeManabu en-aut-sei=Abe en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImamuraYukio en-aut-sei=Imamura en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyasakaTomohiro en-aut-sei=Miyasaka en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KakudaNobuto en-aut-sei=Kakuda en-aut-mei=Nobuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OohashiToshitaka en-aut-sei=Oohashi en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimogoriTomomi en-aut-sei=Shimogori en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamakawaKazuhiro en-aut-sei=Yamakawa en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IkawaMasahito en-aut-sei=Ikawa en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NukinaNobuyuki en-aut-sei=Nukina en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Molecular Biology and Biochemistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University kn-affil= affil-num=3 en-affil=Laboratory of Structural Neuropathology, Graduate School of Brain Science, Doshisha University kn-affil= affil-num=4 en-affil=Department of Animal Model Development, Brain Research Institute, Niigata University kn-affil= affil-num=5 en-affil=Laboratory of Structural Neuropathology, Graduate School of Brain Science, Doshisha University kn-affil= affil-num=6 en-affil=Faculty of Life and Medical Sciences, Doshisha University kn-affil= affil-num=7 en-affil=Faculty of Life and Medical Sciences, Doshisha University kn-affil= affil-num=8 en-affil=Department of Molecular Biology and Biochemistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Laboratory for Molecular Mechanisms of Brain Development, RIKEN Center for Brain Science kn-affil= affil-num=10 en-affil=Laboratory for Neurogenetics, RIKEN Center for Brain Science kn-affil= affil-num=11 en-affil=Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University kn-affil= affil-num=12 en-affil=Laboratory of Structural Neuropathology, Graduate School of Brain Science, Doshisha University kn-affil= en-keyword=Golli-MBP kn-keyword=Golli-MBP en-keyword=Cerebellar granule neuron kn-keyword=Cerebellar granule neuron en-keyword=CRISPR/Cas9 kn-keyword=CRISPR/Cas9 en-keyword=Conditional knockout kn-keyword=Conditional knockout END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=1 article-no= start-page=62 end-page=68 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=What is the identity of Gerota fascia? Histological study with cadavers en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: The advancement of laparoscopic surgery has allowed surgeons to see finer anatomical structures during surgery. As a result, several issues have arisen regarding Gerota fascia that cannot be explained by previous interpretations, such as its various forms observed during surgery. To address these issues, we histologically examined the structure of Gerota fascia.
Methods: Specimens for study were prepared from kidneys with Gerota fascia from four cadavers, and the structure was studied histologically. Its thickness and collagen fiber area ratios were measured using ImageJ and compared to those of the epimysium of the rectus abdominis muscle.
Results: Connective tissue that appeared to be Gerota fascia was observed in 26 specimens. Histologically, the basic structure of Gerota fascia was a sandwich-like structure with a thin layer of thick, long collagen fibers in the central layer, and small granular collagen fibers scattered at the edges. However, not all areas observed had a similar structure; eight specimens were composed only of small granular collagen fibers. The average thickness of the Gerota fascia was 466?μm, and the area ratio of collagen was 27.1%. In contrast, the epimysium was much thicker than Gerota fascia, and its collagen fibers were much thicker and denser.
Conclusions: Gerota fascia, unlike the epimysium, was a very thin and fragile layer of collagen fibers, and its structure was diverse. This explains why Gerota fascia was observed in various states during surgery. It is important for surgeons to understand the properties of Gerota fascia and to treat it appropriately. en-copyright= kn-copyright= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei 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=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=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=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= en-aut-name=SatoKeita en-aut-sei=Sato en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KomiyamaTakaaki en-aut-sei=Komiyama en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MomotaRyusuke en-aut-sei=Momota en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhuchiHideyo en-aut-sei=Ohuchi en-aut-mei=Hideyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= affil-num=1 en-affil=Minimally Invasive Therapy Center, 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=Organ Transplant Center, 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 Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Cytology and Histology, 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= en-keyword=collagen fiber kn-keyword=collagen fiber en-keyword=connective tissue kn-keyword=connective tissue en-keyword=fusion fascia kn-keyword=fusion fascia en-keyword=Gerota fascia kn-keyword=Gerota fascia en-keyword=renal fascia kn-keyword=renal fascia 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=2025 dt-pub=20250728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tailoring Mechanical Properties and Ionic Conductivity of Poly(ionic liquid)-Based Ion Gels by Tuning Anion Compositions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Poly(ionic liquid) (PIL)-based ion gels have emerged as promising materials for advanced electrochemical applications because of their excellent miscibility with ionic liquids (IL), tunable mechanical properties, and high ionic conductivity. Despite extensive studies on PIL-based ion gels, a comprehensive understanding of how different anion combinations in the system affect physicochemical properties is lacking. In this study, we systematically investigate the effect of different anion species, such as bis(trifluoromethanesulfonyl)imide (TFSI) and hexafluorophosphate (PF6), on the mechanical, viscoelastic, and ion conductive behaviors of PIL-based ion gels. We investigate the interplay between anion size, packing density, and polymer segmental dynamics by varying the anion composition in both the PIL network and IL component. Rheological analysis and uniaxial tensile testing results indicate that PF6-containing ion gels exhibit enhanced higher Young’s modulus because of their restricted chain mobility resulting in higher glass transition temperature (Tg). In addition, we confirm the anion exchange between PIL and IL during gel preparation and find that the mechanical and ion conductive properties of the gels are governed by the total molar ratio of anions in the gels. Our findings highlight that tuning the anion composition in PIL-based ion gels provides an effective strategy to tailor their performance, with potential applications for flexible electronics and solid-state electrochemical devices. en-copyright= kn-copyright= en-aut-name=WatanabeTakaichi en-aut-sei=Watanabe en-aut-mei=Takaichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MizutaniYuna en-aut-sei=Mizutani en-aut-mei=Yuna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=OnoTsutomu en-aut-sei=Ono en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=3 en-affil=Material Science and Engineering Department, The Pennsylvania State University, 80 Pollock Road, State College kn-affil= affil-num=4 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= en-keyword=poly(ionic liquid) kn-keyword=poly(ionic liquid) en-keyword=anion exchange kn-keyword=anion exchange en-keyword=gel kn-keyword=gel en-keyword=conductivity kn-keyword=conductivity en-keyword=toughness kn-keyword=toughness END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=24 article-no= start-page=3299 end-page=3306 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Preliminary Survey of Rheumatologists on the Management of Late-onset Rheumatoid Arthritis in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective We investigated the current perspectives regarding the management of late-onset rheumatoid arthritis (LORA) among rheumatologists in clinical practice.
Methods This study was performed in October 2021, and included 65 rheumatologists certified by the Japan College of Rheumatology, who were administered questionnaires (including multiple choice and descriptive formulae) regarding the management of LORA. We aggregated and analyzed the responses.
Results All 65 rheumatologists responded to the survey; 47 (72%) answered that >50% of newly diagnosed patients were aged ?65 years, 42 (65%) answered that achievement of remission or low disease activity was the treatment goal, and 40 (62%) considered patient safety to be the highest priority. Most rheumatologists are concerned about the management of conditions other than RA, such as comorbidities, financial constraints, and life circumstances that interfere with standard or recommended treatment implementation.
Conclusion This preliminary survey highlighted various rheumatologists' perspectives regarding the management of LORA. en-copyright= kn-copyright= en-aut-name=TakanashiSatoshi en-aut-sei=Takanashi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanekoYuko en-aut-sei=Kaneko en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawahitoYutaka en-aut-sei=Kawahito en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KidaTakashi en-aut-sei=Kida en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugiharaTakahiko en-aut-sei=Sugihara en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KojimaToshihisa en-aut-sei=Kojima en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaradaRyozo en-aut-sei=Harada en-aut-mei=Ryozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshitokuMichinori en-aut-sei=Ishitoku en-aut-mei=Michinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HirataShintaro en-aut-sei=Hirata en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HashimotoMotomu en-aut-sei=Hashimoto en-aut-mei=Motomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HidakaToshihiko en-aut-sei=Hidaka en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AbeAsami en-aut-sei=Abe en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshikawaHajime en-aut-sei=Ishikawa en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ItoHiromu en-aut-sei=Ito en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KishimotoMitsumasa en-aut-sei=Kishimoto en-aut-mei=Mitsumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MatsuiKazuo en-aut-sei=Matsui en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsuiToshihiro en-aut-sei=Matsui en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MatsushitaIsao en-aut-sei=Matsushita en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OnishiAkira en-aut-sei=Onishi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MorinobuAkio en-aut-sei=Morinobu en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=AsaiShuji en-aut-sei=Asai en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TanakaEiichi en-aut-sei=Tanaka en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 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=24 ORCID= en-aut-name=KojimaMasayo en-aut-sei=Kojima en-aut-mei=Masayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= affil-num=1 en-affil=Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=4 en-affil=Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=5 en-affil=Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine kn-affil= affil-num=6 en-affil=National Hospital Organization Nagoya Medical Center, Orthopaedic Surgery and Rheumatology kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Kurashiki Sweet Hospital kn-affil= affil-num=8 en-affil=Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital kn-affil= affil-num=9 en-affil=Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital kn-affil= affil-num=10 en-affil=Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Miyazaki-Zenjinkai Hospital kn-affil= affil-num=12 en-affil=Department of Rheumatology, Niigata Rheumatic Center kn-affil= affil-num=13 en-affil=Department of Rheumatology, Niigata Rheumatic Center kn-affil= affil-num=14 en-affil=Kurashiki Central Hospital kn-affil= affil-num=15 en-affil=Department of Nephrology and Rheumatology, Kyorin University School of Medicine kn-affil= affil-num=16 en-affil=Department of Rheumatology, Teine Keijinkai Hospital kn-affil= affil-num=17 en-affil=Department of Rheumatology Research, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital kn-affil= affil-num=18 en-affil=Department of Rehabilitation Medicine, Kanazawa Medical University kn-affil= affil-num=19 en-affil=Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto University kn-affil= affil-num=20 en-affil=Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=21 en-affil=Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=22 en-affil=Department of Orthopaedic Surgery and Rheumatology, Nagoya University Graduate School of Medicine kn-affil= affil-num=23 en-affil=Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine kn-affil= affil-num=24 en-affil=Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine kn-affil= affil-num=25 en-affil=Department of Public Health, Nagoya City University Graduate School of Medical Sciences kn-affil= en-keyword=late-onset rheumatoid arthritis kn-keyword=late-onset rheumatoid arthritis en-keyword=ageing society kn-keyword=ageing society en-keyword=questionnaire kn-keyword=questionnaire END start-ver=1.4 cd-journal=joma no-vol=38 cd-vols= no-issue=9 article-no= start-page=e70105 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250724 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ultrahigh‐Field MR‐Compatible Mechanical Tactile Stimulator for Investigating Somatosensory Processing in Small‐Bodied Animals en-subtitle= kn-subtitle= en-abstract= kn-abstract=Common marmosets (Callithrix jacchus), small-bodied New World primates that share similar sensory processing pathways with human beings, have gained great interests. Their small body size allows imaging of brain activity with high spatial resolution and on a whole-brain scale using ultrahigh-field (UHF) magnetic resonance imaging (MRI) scanners. However, the strong magnetic field and the small size of the hand and forearm pose challenges in delivering tactile stimulation during fMRI experiments. In the present study, we developed an MR-compatible tactile dual-point stimulator to provide high-precision mechanical stimulation for exploring somatosensory processing in small-bodied animals. The study population consisted of a water phantom and three male common marmosets. Cerebral blood volume (CBV) weighted fMRI data were obtained with a gradient echo (GE), echo-planar imaging (EPI) sequence at 7T scanner. The output performance of the device was tested by a pressure sensor. The MR compatibility of the device was verified by measuring the temporal signal-to-noise ratio (tSNR) of a water phantom. To test the effectiveness of tactile stimulation, we conducted block designed tactile stimulation experiments on marmosets. A one-way repeated measures ANOVA was conducted for comparing the tSNR results. We performed one-sample t-tests to investigate the negative response of the forearm and hand stimulation with a threshold of t > 1.96 (p < 0.05). Performance tests revealed that mechanical stimulation (averaged force: 31.69?g) was applied with a delay of 12?ms. Phantom experiments confirmed that there was no significant difference in the tSNR among three (10?Hz, 1?Hz, and no-stimulus) conditions (F (2, 798) = 0.71, p = 0.49). The CBV activity results showed that the stimulator successfully elicited hand and forearm somatosensory activations in primary somatosensory areas. These results indicated that the device is well suited for small-bodied animal somatosensory studies. en-copyright= kn-copyright= en-aut-name=WangChenyu en-aut-sei=Wang en-aut-mei=Chenyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ImaiHirohiko en-aut-sei=Imai en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukunagaMasaki en-aut-sei=Fukunaga en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoHiroki en-aut-sei=Yamamoto en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YuYinghua en-aut-sei=Yu en-aut-mei=Yinghua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SekiKazuhiko en-aut-sei=Seki en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HanakawaTakashi en-aut-sei=Hanakawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UmedaTatsuya en-aut-sei=Umeda en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YangJiajia en-aut-sei=Yang en-aut-mei=Jiajia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=Innovation Research Center for Quantum Medicine, Gifu University School of Medicine kn-affil= affil-num=3 en-affil=Section of Brain Function Information, National Institute for Physiological Sciences kn-affil= affil-num=4 en-affil=Graduate School of Human and Environmental Studies, Kyoto 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=Department of Neurophysiology, National Center of Neurology and Psychiatry kn-affil= affil-num=7 en-affil=Department of Integrated Neuroanatomy and Neuroimaging, Kyoto University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Integrated Neuroanatomy and Neuroimaging, Kyoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=primary somatosensory cortex kn-keyword=primary somatosensory cortex en-keyword=small-bodied animals kn-keyword=small-bodied animals en-keyword=tactile stimulation device kn-keyword=tactile stimulation device en-keyword=ultrahigh-field magnetic resonance imaging kn-keyword=ultrahigh-field magnetic resonance imaging END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue= article-no= start-page=e60943 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250729 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Usefulness of Interventions Using a Smartphone Cognitive Behavior Therapy Application for Children With Mental Health Disorders: Prospective, Single-Arm, Uncontrolled Clinical Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The prevalence of mental health disorders among children in Japan has increased rapidly, and these children often show depressive symptoms and reduced quality of life (QOL). We previously developed a smartphone-based self-monitoring app to deliver cognitive behavioral therapy (CBT), implemented it in healthy children, and reported its effectiveness for health promotion.
Objective: This study aims to examine the usefulness of the CBT app for improvement in depressive symptoms and QOL in children with mental health disorders.
Methods: The participants were 115 children with mental health disorders (eg, school refusal, orthostatic hypotension, eating disorders, developmental disorders, among others) and aged 12‐18 years. The CBT app?based program comprised 1 week of psychoeducation followed by 1 week of self-monitoring. After reading story-like scenarios, participants created a self-monitoring sheet with 5 panels: events, thoughts, feelings, body responses, and actions. All participants received regular mental health care from physicians in addition to the app-based program. To evaluate the participants’ depressive symptoms and QOL, Patient Health Questionnaire for Adolescents (PHQ-9A), Depression Self-Rating Scale for Children (DSRS-C), and Pediatric Quality of Life Inventory (PedsQL) were measured at the beginning of the intervention, and at 2 and 6 months thereafter. Questionnaire for Triage and Assessment with 30 items (QTA30), and Rosenberg Self-Esteem Scale (RSES) were also used to measure their health and self-esteem. Participants were divided into 4 groups on the basis of the PHQ-9A score (above or below the cutoff; PHQ-9A?5 or PHQ-9A<5) and completion or noncompletion of the CBT app?based program (app [+] or app [-]). The primary outcome was improvement in the DSRS-C score, and secondary outcomes were improvement in other psychometric scales including PedsQL, QTA30, and RSE. A paired-samples t test was used for statistical analysis. The Medical Ethics Committee of Fukuoka University Faculty of Medicine (approval U22-05-002) approved the study design.
Results: There were 48, 18, 18, and 7 participants in the PHQ-9A?5 app (+), PHQ-9A?5 app (-), PHQ-9A<5 app (+), and PHQ-9A<5 app (-) groups, respectively. A total of 24 participants dropped out. No improvement in the DSRS-C score was observed in all groups. However, PedsQL scores improved significantly at 2 and 6 months in the PHQ-9A<5 app (+) group (t17=6.62; P<.001 and t17=6.11; P<.001, respectively). There was a significant positive correlation between the PHQ-9A scores and the number of self-monitoring sheets completed.
Conclusions: The CBT app was useful for improving PedsQL scores of children with mental health disorders. However, a higher-intensity CBT program is necessary for more severely depressed children.
Trial Registration: University Hospital Medical Information Network Clinical Trials Registry UMIN000046775; center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053360 en-copyright= kn-copyright= en-aut-name=NagamitsuShinichiro en-aut-sei=Nagamitsu en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkadaAyumi en-aut-sei=Okada en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakutaRyoichi en-aut-sei=Sakuta en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshiiRyuta en-aut-sei=Ishii en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KoyanagiKenshi en-aut-sei=Koyanagi en-aut-mei=Kenshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HabukawaChizu en-aut-sei=Habukawa en-aut-mei=Chizu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatayamaTakashi en-aut-sei=Katayama en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ItoMasaya en-aut-sei=Ito en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KanieAyako en-aut-sei=Kanie en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtaniRyoko en-aut-sei=Otani en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=InoueTakeshi en-aut-sei=Inoue en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KitajimaTasuku en-aut-sei=Kitajima en-aut-mei=Tasuku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsubaraNaoki en-aut-sei=Matsubara en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TanakaChie en-aut-sei=Tanaka en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiiChikako en-aut-sei=Fujii en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShigeyasuYoshie en-aut-sei=Shigeyasu en-aut-mei=Yoshie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsuokaMichiko en-aut-sei=Matsuoka en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KakumaTatsuyuki en-aut-sei=Kakuma en-aut-mei=Tatsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HorikoshiMasaru en-aut-sei=Horikoshi en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Pediatrics, Faculty of Medicine, Fukuoka University 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=Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center kn-affil= affil-num=4 en-affil=Department of Pediatrics & Child Health, Kurume University, School of Medicine kn-affil= affil-num=5 en-affil=Nagasaki Prefectural Center of Medicine and Welfare for Children kn-affil= affil-num=6 en-affil=Department of Pediatric Allergy, Minami Wakayama Medical Center kn-affil= affil-num=7 en-affil=L2B Inc kn-affil= affil-num=8 en-affil=National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry kn-affil= affil-num=9 en-affil=National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry kn-affil= affil-num=10 en-affil=Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center kn-affil= affil-num=11 en-affil=Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center kn-affil= affil-num=12 en-affil=Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center kn-affil= affil-num=13 en-affil=Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center kn-affil= affil-num=14 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Neuropsychiatry, Kurume University School of Medicine kn-affil= affil-num=18 en-affil=Biostatistics Center, Kurume University kn-affil= affil-num=19 en-affil=National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry kn-affil= en-keyword=smartphone kn-keyword=smartphone en-keyword=cognitive behavioral therapy kn-keyword=cognitive behavioral therapy en-keyword=application kn-keyword=application en-keyword=adolescent kn-keyword=adolescent en-keyword=youth kn-keyword=youth en-keyword=teen kn-keyword=teen en-keyword=pediatric kn-keyword=pediatric en-keyword=mental health kn-keyword=mental health en-keyword=psychoeducation kn-keyword=psychoeducation en-keyword=self-monitoring kn-keyword=self-monitoring en-keyword=questionnaire kn-keyword=questionnaire en-keyword=depressive symptoms kn-keyword=depressive symptoms en-keyword=effectiveness kn-keyword=effectiveness en-keyword=Japan kn-keyword=Japan en-keyword=statistical analysis kn-keyword=statistical analysis en-keyword=single-arm uncontrolled study kn-keyword=single-arm uncontrolled study en-keyword=mobile phone kn-keyword=mobile phone END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=1 article-no= start-page=e70146 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Gastric Atypical Lipomatous Tumor/Well‐Differentiated Liposarcoma With Endoscopic Morphological Changes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Atypical lipomatous tumor/well-differentiated liposarcoma is a locally aggressive mesenchymal neoplasm composed of adipocytes and stromal cells. Gastric cases are exceedingly rare, and their malignant potential remains unclear. We report a case of a woman in her 60s who was found to have multiple submucosal tumor-like lesions of the stomach. Over time, the tumors increased in size, requiring a laparoscopic partial gastrectomy. Histological examination revealed a tumor composed of both fatty tissue and fibrous stroma with nuclear atypia. Immunohistochemistry showed positivity for CDK4 and MDM2, and fluorescence in situ hybridization confirmed MDM2 amplification, leading to a diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma. This case presented an unusual gastric manifestation, with multiple submucosal tumor-like lesions on endoscopy and exhibiting progressive morphological changes over several years. 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=OmoteShizuma en-aut-sei=Omote en-aut-mei=Shizuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SonobeHiroshi en-aut-sei=Sonobe en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=ToyokawaTatsuya en-aut-sei=Toyokawa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 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=10 ORCID= affil-num=1 en-affil=Department of Diagnostic Pathology, NHO Fukuyama Medical Center kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Fukuyama Minami Hospital kn-affil= affil-num=3 en-affil=Department of Diagnostic Pathology, NHO Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=5 en-affil=Department of Gastroenterology, NHO Fukuyama Medical Center kn-affil= affil-num=6 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=7 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=10 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=atypical lipomatous tumor kn-keyword=atypical lipomatous tumor en-keyword=CDK4 kn-keyword=CDK4 en-keyword=MDM2 kn-keyword=MDM2 en-keyword=stomach kn-keyword=stomach en-keyword=well-differentiated liposarcoma kn-keyword=well-differentiated liposarcoma END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue= article-no= start-page=104719 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Near-infrared photoimmunotherapy for recurrent cancer at the base of the tongue en-subtitle= kn-subtitle= en-abstract= kn-abstract=Near-infrared photoimmunotherapy (NIR-PIT) is a novel therapeutic approach that targets epidermal growth factor receptor (EGFR). In NIR-PIT, administration of cetuximab sarotalocan sodium is followed by laser irradiation of the affected area, which theoretically should induce tumor cell death. However, residual tumors are occasionally observed. This study investigated factors that influence the therapeutic efficacy of NIR-PIT in cases of recurrence of cancer at the base of the tongue. Six patients undergoing 11 treatment cycles were analyzed, focusing on the puncture interval of cylindrical diffusers and the expression of EGFR in tumors. The results demonstrated that a puncture interval of ?12 mm significantly enhanced therapeutic efficacy, with one case achieving complete response. EGFR expression was positive in all cases and expression score showed no significant change between before and after treatment. These findings suggest that puncture interval plays a critical role in therapeutic outcomes, whereas EGFR expression may not directly influence treatment efficacy. en-copyright= kn-copyright= en-aut-name=MakinoTakuma en-aut-sei=Makino en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaoiYuto en-aut-sei=Naoi en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoJunya en-aut-sei=Matsumoto en-aut-mei=Junya 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=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= 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= en-keyword=ear-infrared photoimmunotherapy (NIR-PIT) kn-keyword=ear-infrared photoimmunotherapy (NIR-PIT) en-keyword=Epidermal growth factor receptor (EGFR) kn-keyword=Epidermal growth factor receptor (EGFR) en-keyword=Cylindrical diffuser kn-keyword=Cylindrical diffuser en-keyword=Puncture interval kn-keyword=Puncture interval en-keyword=Base of tongue cancer kn-keyword=Base of tongue cancer END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=158 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250719 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oncolytic virus-mediated p53 activation boosts the antitumor immunity of a p53-transduced dendritic cell vaccine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dendritic cells (DCs) transduced with replication-deficient, wild-type human p53-expressing adenovirus Ad-p53 (Ad-p53 DCs) induce p53-targeting cytotoxic T lymphocytes (CTLs). However, the antitumor efficacy of Ad-p53 DCs is diminished by weak p53 immunogenicity in tumor cells and poor immune responses. We developed a p53-armed oncolytic adenovirus, OBP-702, to induce tumor-specific p53 expression and antitumor immune response, suggesting a role for OBP-702 in enhancing the antitumor efficacy of Ad-p53 DCs. The combined effect of Ad-p53 DCs and OBP-702 was investigated using murine colon cancer (CC) tumor models. Ad-p53 DCs were obtained by stimulating bone marrow-derived cells with granulocyte-macrophage colony-stimulating factor, interleukin-4, and Ad-p53. Subcutaneous tumor models of CT26 (p53 wild-type) and MC38 (p53 mutant-type) murine CC cell lines were used to evaluate the therapeutic potential of combination therapy in the terms of tumor growth, abscopal effect, antitumor immune response, and presentation of p53 peptides in tumor cells. Combination therapy with Ad-p53 DCs and OBP-702 significantly suppressed the growth of p53-intact CT26 tumors at treated and untreated sites by inducing tumor-infiltration of CD8+ CTLs and CD11c+ DCs. OBP-702-infected tumor cells presented human p53 epitopes in the context of major histocompatibility complex molecules, which were recognized by CTLs induced by Ad-p53 DCs. Combination therapy significantly suppressed the growth of p53-mutant MC38 tumors by activating the antitumor immune response. Our results suggest that OBP-702-mediated presentation of p53 epitopes on tumor cells enhances the antitumor efficacy of Ad-p53 DCs against murine CC tumors by attracting p53-targeting CTLs. en-copyright= kn-copyright= en-aut-name=YamadaMotohiko en-aut-sei=Yamada en-aut-mei=Motohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuemoriKanto en-aut-sei=Suemori en-aut-mei=Kanto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=KajiwaraYoshinori en-aut-sei=Kajiwara en-aut-mei=Yoshinori 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=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InoueHiroaki en-aut-sei=Inoue en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HashimotoNaoyuki en-aut-sei=Hashimoto en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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=12 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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=16 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= 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= affil-num=13 en-affil=Neutron Therapy Research Center, Okayama University Hospital kn-affil= affil-num=14 en-affil=Oncolys BioPharma, Inc kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=199 cd-vols= no-issue= article-no= start-page=108027 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=Real-world status of multimodal treatment of Stage IIIA-N2 non-small cell lung cancer in Japan: Results from the SOLUTION study, a non-interventional, multicenter cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: There is limited consensus on resectability criteria for Stage IIIA-N2 non-small cell lung cancer (NSCLC). We examined the patient characteristics, N2 status, treatment decisions, and clinical outcomes according to the treatment modality for Stage IIIA-N2 NSCLC in Japan.
Materials and methods: Patients with Stage IIIA-N2 NSCLC in Japan were consecutively registered in the SOLUTION study between 2013 and 2014. Patients were divided according to treatment (chemoradiotherapy [CRT], surgery + perioperative therapy [neoadjuvant and/or adjuvant therapy], surgery alone). Demographic characteristics, N2 status (number and morphological features), pathological information, and treatments were analyzed descriptively. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were estimated using the Kaplan?Meier method.
Results: Of 227 patients registered, 133 underwent CRT, 56 underwent surgery + perioperative therapy, and 38 underwent surgery alone. The physicians reported the following reasons for unresectability for 116 of 133 CRT patients: large number of metastatic lymph nodes (70.7 %), extranodal infiltration (25.0 %), poor surgical tolerance (19.0 %), or other reasons (18.1 %). CRT was more frequently performed in patients whose lymph nodes had an infiltrative appearance (64.3 %) and was the predominant treatment in patients with multiple involved stations (discrete: 60.0 %; infiltrative: 80.4 %). Distant metastasis with/without local progression was found in 50.4 %, 50.0 %, and 36.8 % of patients in the CRT, surgery + perioperative therapy, and surgery alone groups, respectively. The respective 3-year OS and DFS/PFS rates (median values) were as follows: surgery + perioperative therapy?61.9 % (not reached) and 37.1 % (22.4 months; DFS); CRT group?42.2 % (31.9 months) and 26.8 % (12.0 months; PFS); surgery alone group?37.7 % (26.5 months) and 28.7 % (12.6 months; DFS).
Conclusion: This study has illuminated the real-world decision rules for choosing between surgical and non-surgical approaches in patients with Stage IIIA-N2 NSCLC. Our landmark data could support treatment decision making for using immune checkpoint inhibitors and targeted therapy for driver oncogenes in the perioperative therapy era. en-copyright= kn-copyright= en-aut-name=HorinouchiHidehito en-aut-sei=Horinouchi en-aut-mei=Hidehito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MurakamiHaruyasu en-aut-sei=Murakami en-aut-mei=Haruyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaHideyuki en-aut-sei=Harada en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SobueTomotaka en-aut-sei=Sobue en-aut-mei=Tomotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoTomohiro en-aut-sei=Kato en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AtagiShinji en-aut-sei=Atagi en-aut-mei=Shinji 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=TokitoTakaaki en-aut-sei=Tokito en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OizumiSatoshi en-aut-sei=Oizumi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SeikeMasahiro en-aut-sei=Seike en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MioTadashi en-aut-sei=Mio en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SoneTakashi en-aut-sei=Sone en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=IwaneTakeshi en-aut-sei=Iwane en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 ORCID= en-aut-name=TsuboiMasahiro en-aut-sei=Tsuboi en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=3 en-affil=Division of Radiation Therapy, Shizuoka Cancer Center kn-affil= affil-num=4 en-affil=Division of Environmental Medicine and Population Sciences, Graduate School of Medicine, Osaka University kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, National Hospital Organization Himeji Medical Cente kn-affil= affil-num=6 en-affil=Department of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical Center kn-affil= affil-num=7 en-affil=Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=8 en-affil=Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center kn-affil= affil-num=10 en-affil=Department of Pulmonary Medicine and Oncology, Nippon Medical School 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, National Hospital Organization Kyoto Medical Center kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Kanazawa University Hospital kn-affil= affil-num=14 en-affil=Department of Medical, AstraZeneca K.K. kn-affil= affil-num=15 en-affil=Department of Medical, AstraZeneca K.K. kn-affil= affil-num=16 en-affil=Department of Medical, AstraZeneca K.K. kn-affil= affil-num=17 en-affil=Department of Thoracic Surgery, National Cancer Center Hospital East kn-affil= en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer en-keyword=Surgery kn-keyword=Surgery en-keyword=Adjuvant therapy kn-keyword=Adjuvant therapy en-keyword=Neoadjuvant therapy kn-keyword=Neoadjuvant therapy en-keyword=Chemoradiotherapy kn-keyword=Chemoradiotherapy en-keyword=Observational study kn-keyword=Observational study en-keyword=Retrospective study kn-keyword=Retrospective study END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=40 article-no= start-page=3355- end-page=3364 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Plain language summary: tarlatamab for patients with previously treated small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=AhnMyung-Ju en-aut-sei=Ahn en-aut-mei=Myung-Ju kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChoByoung Chul en-aut-sei=Cho en-aut-mei=Byoung Chul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FelipEnriqueta en-aut-sei=Felip en-aut-mei=Enriqueta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KorantzisIppokratis en-aut-sei=Korantzis en-aut-mei=Ippokratis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=MajemMargarita en-aut-sei=Majem en-aut-mei=Margarita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Juan-VidalOscar en-aut-sei=Juan-Vidal en-aut-mei=Oscar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HandzhievSabin en-aut-sei=Handzhiev en-aut-mei=Sabin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IzumiHiroki en-aut-sei=Izumi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LeeJong-Seok en-aut-sei=Lee en-aut-mei=Jong-Seok kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DziadziuszkoRafal en-aut-sei=Dziadziuszko en-aut-mei=Rafal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WolfJ?rgen en-aut-sei=Wolf en-aut-mei=J?rgen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=BlackhallFiona en-aut-sei=Blackhall en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ReckMartin en-aut-sei=Reck en-aut-mei=Martin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AlvarezJean Bustamante en-aut-sei=Alvarez en-aut-mei=Jean Bustamante kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HummelHorst-Dieter en-aut-sei=Hummel en-aut-mei=Horst-Dieter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=DingemansAnne-Marie C. en-aut-sei=Dingemans en-aut-mei=Anne-Marie C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SandsJacob en-aut-sei=Sands en-aut-mei=Jacob kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=AkamatsuHiroaki en-aut-sei=Akamatsu en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OwonikokoTaofeek K. en-aut-sei=Owonikoko en-aut-mei=Taofeek K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=RamalingamSuresh S. en-aut-sei=Ramalingam en-aut-mei=Suresh S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=BorghaeiHossein en-aut-sei=Borghaei en-aut-mei=Hossein kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=JohnsonMelissa L. en-aut-sei=Johnson en-aut-mei=Melissa L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HuangShuang en-aut-sei=Huang en-aut-mei=Shuang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=MukherjeeSujoy en-aut-sei=Mukherjee en-aut-mei=Sujoy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=MinochaMukul en-aut-sei=Minocha en-aut-mei=Mukul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=JiangTony en-aut-sei=Jiang en-aut-mei=Tony kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MartinezPablo en-aut-sei=Martinez en-aut-mei=Pablo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=AndersonErik S. en-aut-sei=Anderson en-aut-mei=Erik S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=Paz-AresLuis en-aut-sei=Paz-Ares en-aut-mei=Luis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Samsung Medical Center, Sungkyunkwan University School of Medicine kn-affil= affil-num=2 en-affil=Yonsei Cancer Center, Yonsei University College of Medicine kn-affil= affil-num=3 en-affil=Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology kn-affil= affil-num=4 en-affil=Department of Medical Oncology, Saint Loukas Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Hospital de la Santa Creu i Sant Pau kn-affil= affil-num=7 en-affil= kn-affil= affil-num=8 en-affil=Klinische Abteilung f?r Pneumologie, Universit?tsklinikum Krems kn-affil= affil-num=9 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital East kn-affil= affil-num=10 en-affil=Seoul National University Bundang Hospital kn-affil= affil-num=11 en-affil=Department of Oncology and Radiotherapy and Early Phase Clinical Trials Center, Medical University of Gdansk kn-affil= affil-num=12 en-affil=Department of Internal Medicine, Center for Integrated Oncology, University Hospital Cologne kn-affil= affil-num=13 en-affil=Christie NHS Foundation Trust and University of Manchester kn-affil= affil-num=14 en-affil=Lungen Clinic, Airway Research Center North, German Center for Lung Research kn-affil= affil-num=15 en-affil=West Virginia University Health Sciences Center kn-affil= affil-num=16 en-affil=Translational Oncology?Early Clinical Trial Unit, Comprehensive Cancer Center Mainfranken and Bavarian Cancer Research Center, Universit?tsklinikum W?rzburg kn-affil= affil-num=17 en-affil=Department of Pulmonary Medicine, Erasmus MC Cancer Institute kn-affil= affil-num=18 en-affil=Dana?Farber Cancer Institute, Harvard Medical School kn-affil= affil-num=19 en-affil=Wakayama Medical University Hospital kn-affil= affil-num=20 en-affil=Division of Hematology?Oncology, Hillman Cancer Center, University of Pittsburgh Medical Center kn-affil= affil-num=21 en-affil=Winship Cancer Institute of Emory University kn-affil= affil-num=22 en-affil=Fox Chase Cancer Center kn-affil= affil-num=23 en-affil=Sarah Cannon Research Institute at Tennessee Oncology kn-affil= affil-num=24 en-affil=Amgen kn-affil= affil-num=25 en-affil=Amgen kn-affil= affil-num=26 en-affil=Amgen kn-affil= affil-num=27 en-affil=Amgen kn-affil= affil-num=28 en-affil=Amgen kn-affil= affil-num=29 en-affil=Amgen kn-affil= affil-num=30 en-affil=Hospital Universitario 12 de Octubre, CNIO-H12o Lung Cancer Unit, Complutense University and Ciberonc kn-affil= en-keyword=Clinical trials kn-keyword=Clinical trials en-keyword=DeLLphi-301 kn-keyword=DeLLphi-301 en-keyword=DLL3 kn-keyword=DLL3 en-keyword=Immunotherapy kn-keyword=Immunotherapy en-keyword=SCLC kn-keyword=SCLC en-keyword=Small cell lung cancer kn-keyword=Small cell lung cancer en-keyword=T cell kn-keyword=T cell en-keyword=Tarlatamab kn-keyword=Tarlatamab END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=24117 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250706 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Survival days of patients with metastatic spinal tumors of lung cancer requiring surgery: a prospective multicenter study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Surgery for metastatic spinal tumors has improved postoperative activities of daily living. A few studies reported on prognostic factors assessed in large multicenter prospective studies for metastatic spinal tumors of lung cancer origin. This study aimed to determine preoperative prognostic factors in patients undergoing surgery for metastatic spinal tumors associated with lung cancer. This prospective registry study included 74 patients diagnosed and operated with metastatic spine tumors derived from lung cancer in 39 high-volume cancer centers. We examined the postoperative survival period and the preoperative factors related to postoperative survival time. We conducted univariate and multivariate Cox regression analyses to determine preoperative prognostic factors. The mean postoperative survival period was 343 days. Multivariate Cox regression analysis revealed a higher feeding score of vitality index, indications for molecularly targeted therapy, and a higher mobility score of Barthel index as independent factors associated with postoperative survival time in metastatic spinal tumors derived from lung cancer. Patients with indications for molecular-targeted therapy and good vitality exhibited longer survival. These results may help in surgical selection for patients with metastatic spinal tumors derived from lung cancer. en-copyright= kn-copyright= en-aut-name=TakahashiTakuya en-aut-sei=Takahashi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiraiTakashi en-aut-sei=Hirai en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShirataniYuki en-aut-sei=Shiratani en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiAkinobu en-aut-sei=Suzuki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KakutaniKenichiro en-aut-sei=Kakutani en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatoSatoshi en-aut-sei=Kato en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TominagaHiroyuki en-aut-sei=Tominaga en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InoueHirokazu en-aut-sei=Inoue en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SawadaHirokatsu en-aut-sei=Sawada en-aut-mei=Hirokatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakegamiNorihiko en-aut-sei=Takegami en-aut-mei=Norihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakanishiKazuo en-aut-sei=Nakanishi en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakajimaHideaki en-aut-sei=Nakajima en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshiharaMasayuki en-aut-sei=Ishihara en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OshigiriTsutomu en-aut-sei=Oshigiri en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FunayamaToru en-aut-sei=Funayama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IimuraTakuya en-aut-sei=Iimura en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TanishimaShinji en-aut-sei=Tanishima en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakashimaHiroaki en-aut-sei=Nakashima en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamabeDaisuke en-aut-sei=Yamabe en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HashimotoKo en-aut-sei=Hashimoto en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 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=21 ORCID= en-aut-name=FunabaMasahiro en-aut-sei=Funaba en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=NagoshiNarihito en-aut-sei=Nagoshi en-aut-mei=Narihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KobayakawaKazu en-aut-sei=Kobayakawa en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YoshiiToshitaka en-aut-sei=Yoshii en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=WatanabeKazuyuki en-aut-sei=Watanabe en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=NakamaeToshio en-aut-sei=Nakamae en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=KaitoTakashi en-aut-sei=Kaito en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=InoueGen en-aut-sei=Inoue en-aut-mei=Gen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=ImagamaShiro en-aut-sei=Imagama en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=WatanabeKota en-aut-sei=Watanabe en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=FuruyaTakeo en-aut-sei=Furuya en-aut-mei=Takeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Institute of Science Tokyo kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Institute of Science Tokyo kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Osaka Metropolitan University kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=8 en-affil=Rehabilitation Center, Jichi Medical University Hospital kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Nihon University School of Medicine kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Mie University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery, Kawasaki Medical School kn-affil= affil-num=12 en-affil=Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui kn-affil= affil-num=13 en-affil=Department of Orthopaedic surgery, Kansai Medical University Hospital kn-affil= affil-num=14 en-affil=Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine kn-affil= affil-num=15 en-affil=Department of Orthopaedic Surgery Institute of Medicine, University of Tsukuba kn-affil= affil-num=16 en-affil=Department of Orthopaedic Surgery, Dokkyo Medical University kn-affil= affil-num=17 en-affil=Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=18 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Orthopaedic Surgery, Iwate Medical University kn-affil= affil-num=20 en-affil=Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=22 en-affil=Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine kn-affil= affil-num=23 en-affil=Department of Orthopaedic Surgery, Keio University kn-affil= affil-num=24 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=25 en-affil=Department of Orthopedic Surgery, Institute of Science Tokyo kn-affil= affil-num=26 en-affil=Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine kn-affil= affil-num=27 en-affil=Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=28 en-affil=Department of Orthopedic Surgery, Osaka University Graduate School of Medicine kn-affil= affil-num=29 en-affil=Department of Orthopaedic Surgery, Kitasato University School of Medicine kn-affil= affil-num=30 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=31 en-affil=Department of Orthopaedic Surgery, Keio University kn-affil= affil-num=32 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University kn-affil= en-keyword=Metastatic spinal tumor kn-keyword=Metastatic spinal tumor en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Postoperative survival period kn-keyword=Postoperative survival period en-keyword=Barthel index kn-keyword=Barthel index en-keyword=Vitality index kn-keyword=Vitality index en-keyword=Molecularly targeted therapy kn-keyword=Molecularly targeted therapy END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=5 article-no= start-page=594 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Review Article: Diagnostic Paradigm Shift in Spine Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Meticulous clinical examination is essential for spinal disorders to utilize the diagnostic methods and technologies that strongly support physicians and enhance clinical practice. A significant change in the approach to diagnosing spinal disorders has occurred in the last three decades, which has enhanced a more nuanced understanding of spine pathology. Traditional radiographic methods such as conventional and functional X-rays and CT scans are still the first line in the diagnosis of spinal disorders due to their low cost and accessibility. As more advanced imaging technologies become increasingly available worldwide, there is a constantly increasing trend in MRI scans for detecting spinal pathologies and making treatment decisions. Not only do MRI scans have superior diagnostic capabilities, but they also assist surgeons in performing meticulous preoperative planning, making them currently the most widely used diagnostic tool for spinal disorders. Positron Emission Tomography (PET) can help detect inflammatory lesions, infections, and tumors. Other advanced diagnostic tools such as CT/MRI fusion image, Functional Magnetic Resonance Imaging (fMRI), Upright and Kinetic MRI, magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI) could play an important role when it comes to detecting more special pathologies. However, some technical difficulties in the daily praxis and their high costs act as obstacles to their further spread. Integrating artificial intelligence and advancements in data analytics and virtual reality promises to enhance spinal procedures’ precision, safety, and efficacy. As these technologies continue to develop, they will play a critical role in transforming spinal surgery. This paradigm shift emphasizes the importance of continuous innovation and adaptability in improving the diagnosis and treatment of spinal disorders. en-copyright= kn-copyright= en-aut-name=LeventAras Efe en-aut-sei=Levent en-aut-mei=Aras Efe 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=HengChristian en-aut-sei=Heng en-aut-mei=Christian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NikolaosSalamalikis en-aut-sei=Nikolaos en-aut-mei=Salamalikis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LatkaKajetan en-aut-sei=Latka en-aut-mei=Kajetan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyamotoAkiyoshi en-aut-sei=Miyamoto en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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=10 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=11 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=12 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Okayama Rosai 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 Rosai Hospital kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= en-keyword=diagnosis kn-keyword=diagnosis en-keyword=spine surgery kn-keyword=spine surgery en-keyword=innovative technique kn-keyword=innovative technique en-keyword=MRI kn-keyword=MRI en-keyword=myelography kn-keyword=myelography END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=4 article-no= start-page=2286 end-page=2299 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202411 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Palliative Surgical Treatment for Spinal Metastases on the Patient’s Quality of Life With a Focus on the Segment of the Metastasis: A Prospective Multicenter Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Study Design: Prospective multicenter study.
Objectives: Palliative surgery is crucial for maintaining the quality of life (QOL) in patients with spinal metastases. This study aimed to compare the short-term outcomes of QOL after palliative surgery between patients with metastatic spinal tumors at different segments.
Methods: We prospectively compared the data of 203 patients with spinal metastases at 2-3 consecutive segments who were divided into the following three groups: cervical, patients with cervical spine lesions; thoracic, patients with upper?middle thoracic spine lesions; and TL/L/S, patients with lesions at the thoracolumbar junction and lumbar and sacral regions. Preoperative and postoperative EuroQol 5-dimension (EQ5D) 5-level were compared.
Results: All groups exhibited improvement in the Frankel grade, performance status, pain, Barthel index, EQ5D health state utility value (HSUV), and EQ5D visual analog scale (VAS) postoperatively. Although preoperative EQ5D HSUVs did not significantly differ between the groups (cervical, 0.461 ± 0.291; thoracic, 0.321 ± 0.292; and TL/L/S, 0.376 ± 0.272), the thoracic group exhibited significantly lower postoperative EQ5D HSUVs than the other two groups (cervical, 0.653 ± 0.233; thoracic, 0.513 ± 0.252; and TL/L/S, 0.624 ± 0.232). However, postoperative EQ5D VAS was not significantly different between the groups (cervical, 63.4 ± 25.8; thoracic, 54.7 ± 24.5; and TL/L/S, 61.7 ± 21.9).
Conclusions: Palliative surgery for metastatic spinal tumors provided comparable QOL improvement, irrespective of the spinal segment involved. Patients with upper and middle thoracic spinal metastases had poorer QOL outcomes than those with metastases in other segments; however, sufficient QOL improvement was achieved. en-copyright= kn-copyright= en-aut-name=SegiNaoki en-aut-sei=Segi en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakashimaHiroaki en-aut-sei=Nakashima en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItoSadayuki en-aut-sei=Ito en-aut-mei=Sadayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OuchidaJun en-aut-sei=Ouchida en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShirataniYuki en-aut-sei=Shiratani en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimizuTakaki en-aut-sei=Shimizu en-aut-mei=Takaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzukiAkinobu en-aut-sei=Suzuki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TeraiHidetomi en-aut-sei=Terai en-aut-mei=Hidetomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KakutaniKenichiro en-aut-sei=Kakutani en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KandaYutaro en-aut-sei=Kanda en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TominagaHiroyuki en-aut-sei=Tominaga en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawamuraIchiro en-aut-sei=Kawamura en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshiharaMasayuki en-aut-sei=Ishihara en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=PakuMasaaki en-aut-sei=Paku en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakahashiYohei en-aut-sei=Takahashi en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FunabaMasahiro en-aut-sei=Funaba en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FunayamaToru en-aut-sei=Funayama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakajimaHideaki en-aut-sei=Nakajima en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=AkedaKoji en-aut-sei=Akeda en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HiraiTakashi en-aut-sei=Hirai en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=InoueHirokazu en-aut-sei=Inoue en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=NakanishiKazuo en-aut-sei=Nakanishi en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FunaoHaruki en-aut-sei=Funao en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OshigiriTsutomu en-aut-sei=Oshigiri en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=OtsukiBungo en-aut-sei=Otsuki en-aut-mei=Bungo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KobayakawaKazu en-aut-sei=Kobayakawa en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TanishimaShinji en-aut-sei=Tanishima en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=HashimotoKo en-aut-sei=Hashimoto en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=IimuraTakuya en-aut-sei=Iimura en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SawadaHirokatsu en-aut-sei=Sawada en-aut-mei=Hirokatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 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=31 ORCID= en-aut-name=ManabeHiroaki en-aut-sei=Manabe en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=IwaiChizuo en-aut-sei=Iwai en-aut-mei=Chizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=YamabeDaisuke en-aut-sei=Yamabe en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=HiyamaAkihiko en-aut-sei=Hiyama en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=SekiShoji en-aut-sei=Seki en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=GotoYuta en-aut-sei=Goto en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=MiyazakiMasashi en-aut-sei=Miyazaki en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=WatanabeKazuyuki en-aut-sei=Watanabe en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=NakamaeToshio en-aut-sei=Nakamae en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=KaitoTakashi en-aut-sei=Kaito en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=NagoshiNarihito en-aut-sei=Nagoshi en-aut-mei=Narihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=KatoSatoshi en-aut-sei=Kato en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=WatanabeKota en-aut-sei=Watanabe en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=ImagamaShiro en-aut-sei=Imagama en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=InoueGen en-aut-sei=Inoue en-aut-mei=Gen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=FuruyaTakeo en-aut-sei=Furuya en-aut-mei=Takeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Chiba University Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Osaka Metropolitan University kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Osaka Metropolitan University kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=12 en-affil=Department of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=13 en-affil=Department of Orthopaedic Surgery, Kansai Medial University Hospital kn-affil= affil-num=14 en-affil=Department of Orthopaedic Surgery, Kansai Medial University Hospital kn-affil= affil-num=15 en-affil=Department of Orthopaedic Surgery, Keio University kn-affil= affil-num=16 en-affil=Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine kn-affil= affil-num=17 en-affil=Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba kn-affil= affil-num=18 en-affil=Department of Orthopaedics and Rehabilitation Medicine, University of Fukui Faculty of Medical Sciences kn-affil= affil-num=19 en-affil=Department of Orthopaedic Surgery, Mie University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Orthopedic Surgery, Tokyo Medical and Dental University kn-affil= affil-num=21 en-affil=Rehabilitation Center, Jichi Medical University Hospital kn-affil= affil-num=22 en-affil=Department of Orthopaedic Surgery, Kawasaki Medical School kn-affil= affil-num=23 en-affil=Department of Orthopaedic Surgery, International University of Health and Welfare Narita Hospital kn-affil= affil-num=24 en-affil=Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine kn-affil= affil-num=25 en-affil=Department of Orthopaedic Surgery, Kyoto University Hospital kn-affil= affil-num=26 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=27 en-affil=Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=28 en-affil=Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=29 en-affil=Department of Orthopaedic Surgery, Dokkyo Medical University kn-affil= affil-num=30 en-affil=Department of Orthopaedic Surgery, Nihon University School of Medicine kn-affil= affil-num=31 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=32 en-affil=Department of Orthopedics, Tokushima University kn-affil= affil-num=33 en-affil=Department of Orthopaedic Surgery, Gifu University Hospital kn-affil= affil-num=34 en-affil=Department of Orthopaedic Surgery, Iwate Medical University kn-affil= affil-num=35 en-affil=Department of Orthopaedic Surgery, Tokai University School of Medicine kn-affil= affil-num=36 en-affil=Department of Orthopaedic Surgery, University of Toyama kn-affil= affil-num=37 en-affil=Department of Orthopaedic Surgery, Nagoya City University kn-affil= affil-num=38 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=39 en-affil=Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine kn-affil= affil-num=40 en-affil=Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=41 en-affil=Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine kn-affil= affil-num=42 en-affil=Department of Orthopaedic Surgery, Keio University kn-affil= affil-num=43 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=44 en-affil=Department of Orthopaedic Surgery, Keio University kn-affil= affil-num=45 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=46 en-affil=Department of Orthopaedic Surgery, Kitasato University School of Medicine kn-affil= affil-num=47 en-affil=Department of Orthopaedic Surgery, Chiba University Hospital kn-affil= en-keyword=spinal metastasis kn-keyword=spinal metastasis en-keyword=metastasis segment kn-keyword=metastasis segment en-keyword=palliative surgery kn-keyword=palliative surgery en-keyword=quality of life kn-keyword=quality of life en-keyword=activities of daily living kn-keyword=activities of daily living en-keyword=pain kn-keyword=pain en-keyword=anxiety kn-keyword=anxiety END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=4 article-no= start-page=616 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Novel Technique for Basilar Invagination Treatment in a Patient with Klippel?Feil Syndrome: A Clinical Example and Brief Literature Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives and Background: To present a novel technique of treatment for a patient with basilar invagination. Basilar invagination (BI) is a congenital condition that can compress the cervicomedullary junction, leading to neurological deficits. Severe cases require surgical intervention, but there is debate over the choice of approach. The anterior approach allows direct decompression but carries high complication rates, while the posterior approach provides indirect decompression and offers good stability with fewer complications. Materials and Methods: A 15-year-old boy with severe myelopathy presented to our hospital with neck pain, bilateral upper limb muscle weakness, and hand numbness persisting for 4 years. Additionally, he experienced increased numbness and gait disturbance three months before his visit. On examination, he exhibited hyperreflexia in both upper and lower limbs, muscle weakness in the bilateral upper limbs (MMT 4), bilateral hypoesthesia below the elbow and in both legs, mild urinary and bowel incontinence, and a spastic gait. Radiographs revealed severe basilar invagination (BI). Preoperative images showed severe BI and that the spinal cord was severely compressed with odontoid process. Results: The patient underwent posterior surgery with the C-arm free technique. All screws including occipital screws were inserted into the adequate position under navigation guidance. Reduction was achieved with skull rotation and distraction. A follow-up at one year showed the following results: Manual muscle testing results and sensory function tests showed almost full recovery, with bilateral arm recovery (MMT 5) and smooth walking. The cervical Japanese Orthopedic Association score of the patient improved from 9/17 to 16/17. Postoperative images showed excellent spinal cord decompression, and no major or severe complications had occurred. Conclusions: Basilar invagination alongside Klippel?Feil syndrome represents a relatively uncommon condition. Utilizing a posterior approach for treating reducible BI with a C-arm-free technique proved to be a safe method in addressing severe myelopathy. This novel navigation technique yields excellent outcomes for patients with BI. 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=AskarAbd El Kader Al en-aut-sei=Askar en-aut-mei=Abd El Kader Al 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=AratakiShinya en-aut-sei=Arataki en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=TaokaTakuya en-aut-sei=Taoka en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama Rosai Hospital 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=Department of Orthopaedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= en-keyword=basilar invagination kn-keyword=basilar invagination en-keyword=Klippel?Feil syndrome kn-keyword=Klippel?Feil syndrome en-keyword=navigation kn-keyword=navigation en-keyword=C-arm free kn-keyword=C-arm free en-keyword=novel technique kn-keyword=novel technique END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=23 article-no= start-page=2715 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Predicting Surgical Site Infections in Spine Surgery: Association of Postoperative Lymphocyte Reduction en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Postoperative lymphopenia is reported as an excellent indicator to predict surgical-site infection (SSI) after spine surgery. However, there is still controversy concerning which serological markers can predict spinal SSI. This study aims to evaluate excellent and early indicators for detecting SSI, focusing on spine instrumented surgery. Materials and Methods: This study included 268 patients who underwent spinal instrumented surgery from January 2022 to December 2023 (159 female and 109 male, average 62.9 years). The SSI group included 20 patients, and the non-SSI group comprised 248 patients. Surgical time, intraoperative blood loss, and glycemic levels were measured in both groups. The complete blood cell counts, differential counts, albumin, and C-reactive protein (CRP) levels were measured pre-surgery and postoperative on Days 1, 3, and 7. In comparing the groups, the Mann?Whitney U test analysis was used for continuous variables, while the chi-squared test and Fisher’s exact test were used for dichotomous variables. Results: The incidence of SSI after spinal instrumentation was 7.46% and was relatively higher in scoliosis surgery. The SSI group had significantly longer surgical times (248 min vs. 180 min, p = 0.0004) and a higher intraoperative blood loss (772 mL vs. 372 mL, p < 0.0001) than the non-SSI group. In the SSI group, the Day 3 (10.5 ± 6.2% vs. 13.8 ± 6.0%, p = 0.012) and Day 7 (14.4 ± 4.8% vs. 18.8 ± 7.1%, p = 0.012) lymphocyte ratios were lower than the non-SSI group. Albumin levels on Day 1 in the SSI group were lower than in the non-SSI group (2.94 ± 0.30 mg/dL vs. 3.09 ± 0.38 mg/dL, p = 0.045). There is no difference in CRP and lymphocyte count between the two groups. Conclusions: SSI patients had lower lymphocyte percentages than non-SSI patients, which was a risk factor for SSI, with constant high inflammation. The Day 3 lymphocyte percentage may predict SSI after spinal instrumented surgery. en-copyright= kn-copyright= en-aut-name=MiyamotoAkiyoshi en-aut-sei=Miyamoto en-aut-mei=Akiyoshi 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=FloresAngel Oscar Paz en-aut-sei=Flores en-aut-mei=Angel Oscar Paz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YuDongwoo en-aut-sei=Yu en-aut-mei=Dongwoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=JainMukul en-aut-sei=Jain en-aut-mei=Mukul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HengChristan en-aut-sei=Heng en-aut-mei=Christan 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=OdaYoshiaki en-aut-sei=Oda en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Okayama Rosai 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 Rosai Hospital kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= en-keyword=surgical site infection kn-keyword=surgical site infection en-keyword=spine surgery kn-keyword=spine surgery en-keyword=instrumentation kn-keyword=instrumentation en-keyword=diagnosis kn-keyword=diagnosis en-keyword=lymphocyte kn-keyword=lymphocyte END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=4 article-no= start-page=519 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240322 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Retrospective Cohort Study of Early versus Delayed Ballon Kyphoplasty Intervention for Osteoporotic Vertebral Fracture Treatment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To investigate the outcomes of early balloon kyphoplasty (BKP) intervention compared with late intervention for osteoporotic vertebral fracture (OVF). Background: Osteoporotic vertebral fracture can lead to kyphotic deformity, severe back pain, depression, and disturbances in activities of daily living (ADL). Balloon kyphoplasty has been widely utilized to treat symptomatic OVFs and has proven to be a very effective surgical option for this condition. Furthermore, BKP is relatively a safe and effective method due to its reduced acrylic cement leakage and greater kyphosis correction. Materials and Methods: A retrospective cohort study was conducted at our hospital for patients who underwent BKP for osteoporotic vertebral fractures in the time frame between January 2020 and December 2022. Ninety-nine patients were included in this study, and they were classified into two groups: in total, 36 patients underwent early BKP intervention (EI) at <4 weeks, and 63 patients underwent late BKP intervention (LI) at ?4 weeks. We performed a clinical, radiological and statistical comparative evaluation for the both groups with a mean follow-up of one year. Results: Adjacent segmental fractures were more frequently observed in the LI group compared to the EI group (33.3% vs. 13.9%, p = 0.034). There was a significant improvement in postoperative vertebral angles in both groups (p = 0.036). The cement volume injected was 7.42 mL in the EI, compared with 6.3 mL in the LI (p = 0.007). The mean surgery time was shorter in the EI, at 30.2 min, compared with 37.1 min for the LI, presenting a significant difference (p = 0.0004). There was no statistical difference in the pain visual analog scale (VAS) between the two groups (p = 0.711), and there was no statistical difference in cement leakage (p = 0.192). Conclusions/Level of Evidence: Early BKP for OVF treatment may achieve better outcomes and fewer adjacent segmental fractures than delayed intervention. en-copyright= kn-copyright= en-aut-name=MiyamotoAkiyoshi en-aut-sei=Miyamoto en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PariharUmesh en-aut-sei=Parihar en-aut-mei=Umesh 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=El Kader Al AskarAbd en-aut-sei=El Kader Al Askar en-aut-mei=Abd kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 ORCID= en-aut-name=TaokaTakuya en-aut-sei=Taoka en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=FujiwaraYoshihiro en-aut-sei=Fujiwara en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama Rosai Hospital 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=Department of Orthopaedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama Rosai Hospital 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 Rosai Hospital kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery, Okayama Rosai Hospital kn-affil= en-keyword=ballon kyphoplasty kn-keyword=ballon kyphoplasty en-keyword=osteoporotic vertebral fractures kn-keyword=osteoporotic vertebral fractures en-keyword=kyphosis kn-keyword=kyphosis END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=209 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exercise hemodynamic evaluation in the management of dasatinib-related pulmonary arterial hypertension: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Dasatinib-related pulmonary arterial hypertension is a rare complication of chronic therapy for hematological malignancies. Pulmonary hypertension often persists despite drug discontinuation and might require vasodilators. Normalizing pulmonary hemodynamics and avoiding the long-term use of vasodilators is challenging.
Case presentation Patient was a 55-year-old Japanese man complaining of progressive dyspnea on effort and fatigue. He had a history of hypertension and chronic myeloid leukemia treated with dasatinib. He was diagnosed with dasatinib-related pulmonary arterial hypertension by a right heart catheterization at rest, demonstrating a mean pulmonary artery pressure of 31 mmHg and a normal pulmonary arterial wedge pressure of 6 mmHg. Symptoms and hemodynamics significantly improved after the discontinuation of dasatinib and the initiation of upfront combination therapy of vasodilators. An exercise right heart catheterization, performed more than 2 years after the initiation of vasodilators, showed a mean pulmonary artery pressure of 15 mmHg at rest and 29 mmHg at peak exercise (normal reference value,? Conclusions The evaluation of pulmonary microcirculation by exercise right heart catheterization can be useful for withdrawing pulmonary vasodilators safely in the management of patients with dasatinib-related pulmonary arterial hypertension. en-copyright= kn-copyright= en-aut-name=YamashitaShuhei en-aut-sei=Yamashita en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiraideTakahiro en-aut-sei=Hiraide en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShiraishiYasuyuki en-aut-sei=Shiraishi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsumataYoshinori en-aut-sei=Katsumata en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KataokaMasaharu en-aut-sei=Kataoka en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuiShogo en-aut-sei=Fukui en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawakamiMichiyuki en-aut-sei=Kawakami en-aut-mei=Michiyuki 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= en-aut-name=OkamotoShinichiro en-aut-sei=Okamoto en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukudaKeiichi en-aut-sei=Fukuda en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IedaMasaki en-aut-sei=Ieda en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=4 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=5 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=6 en-affil=Department of Rehabilitation, Keio University Hospital kn-affil= affil-num=7 en-affil=Department of Rehabilitation, Keio University School of Medicine kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine Academic Field, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Hematology, Keio University School of Medicine kn-affil= affil-num=10 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=11 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= en-keyword=Case report kn-keyword=Case report en-keyword=Dasatinib kn-keyword=Dasatinib en-keyword=Drug-induced kn-keyword=Drug-induced en-keyword=Exercise-induced pulmonary hypertension kn-keyword=Exercise-induced pulmonary hypertension en-keyword=Pulmonary arterial hypertension kn-keyword=Pulmonary arterial hypertension END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=2 article-no= start-page=euaf024 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SCN5A variant type-dependent risk prediction in Brugada syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims The variant in SCN5A with the loss of function (LOF) effect in the cardiac Na+ channel (Nav1.5) is the definitive cause for Brugada syndrome (BrS), and the functional analysis data revealed that LOF variants are associated with poor prognosis. However, which variant types (e.g. missense or non-missense) affect the prognoses of those variant carriers remain unelucidated.
Methods and results We defined SCN5A LOF variants as all non-missense and missense variants that produce peak INa < 65% of wild-type previously confirmed by patch-clamp studies. The study population consisted of 76 Japanese BrS patients (74% patients were male and the median age [IQR] at diagnosis was 28 [14?45] years) with LOF type of SCN5A variants: 40 with missense and 36 with non-missense variants. Non-missense variant carriers presented significantly more severe cardiac conduction disorder compared to the missense variant carriers. During follow-up periods of 9.0 [5.0?14.0] years, compared to missense variants, non-missense variants were significant risk factors of lifetime lethal arrhythmia events (LAEs) (P = 0.023). When focusing only on the missense variants that produce no peak INa, these missense variant carriers exhibited the same clinical outcomes as those with non-missense (log-rank P = 0.325). After diagnosis, however, both variant types were comparable in risk of LAEs (P = 0.155).
Conclusion We identified, for the first time, that SCN5A non-missense variants were associated with higher probability of LAE than missense variants in BrS patients though it did not change significantly after diagnosis. en-copyright= kn-copyright= en-aut-name=AizawaTakanori en-aut-sei=Aizawa en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MakiyamaTakeru en-aut-sei=Makiyama en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuangHai en-aut-sei=Huang en-aut-mei=Hai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImamuraTomohiko en-aut-sei=Imamura en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukuyamaMegumi en-aut-sei=Fukuyama en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SonodaKeiko en-aut-sei=Sonoda en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatoKoichi en-aut-sei=Kato en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraYuko en-aut-sei=Nakamura en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HoshinoKenji en-aut-sei=Hoshino en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OzawaJunichi en-aut-sei=Ozawa en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SuzukiHiroshi en-aut-sei=Suzuki en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YasudaKazushi en-aut-sei=Yasuda en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AokiHisaaki en-aut-sei=Aoki en-aut-mei=Hisaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KuritaTakashi en-aut-sei=Kurita en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YoshidaYoko en-aut-sei=Yoshida en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SuzukiTsugutoshi en-aut-sei=Suzuki en-aut-mei=Tsugutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 ORCID= en-aut-name=OgawaYoshiharu en-aut-sei=Ogawa en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YamagamiShintaro en-aut-sei=Yamagami en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 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=22 ORCID= en-aut-name=FukudaMasakazu en-aut-sei=Fukuda en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OnoMakoto en-aut-sei=Ono en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KondoHidekazu en-aut-sei=Kondo en-aut-mei=Hidekazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=TakahashiNaohiko en-aut-sei=Takahashi en-aut-mei=Naohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=OhnoSeiko en-aut-sei=Ohno en-aut-mei=Seiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NakagawaYoshihisa en-aut-sei=Nakagawa en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=OnoKoh en-aut-sei=Ono en-aut-mei=Koh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=HorieMinoru en-aut-sei=Horie en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine , 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 , kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= affil-num=6 en-affil=Medical Genome Center, National Cerebral and Cardiovascular Center kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= affil-num=8 en-affil=Department of Public Health, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Tsuchiura Kyodo General Hospital kn-affil= affil-num=10 en-affil=Department of Cardiology, Saitama Children’s Medical Center kn-affil= affil-num=11 en-affil=Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=12 en-affil=Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital kn-affil= affil-num=13 en-affil=Department of Pediatric Cardiology, Aichi Children’s Health and Medical Center kn-affil= affil-num=14 en-affil=Department of Pediatric Cardiology, Osaka Women’s and Children’s Hospital kn-affil= affil-num=15 en-affil=Division of Cardiovascular Center, Kindai University School of Medicine kn-affil= affil-num=16 en-affil=Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital kn-affil= affil-num=17 en-affil=Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital kn-affil= affil-num=18 en-affil=Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital kn-affil= affil-num=19 en-affil=Division of Cardiology, Hyogo Prefectural Kobe Children’s Hospital kn-affil= affil-num=20 en-affil=Department of Cardiology, Tenri Hospital kn-affil= affil-num=21 en-affil=Department of Cardiovascular Therapeutics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=22 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=24 en-affil=Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=25 en-affil=Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University kn-affil= affil-num=26 en-affil=Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University kn-affil= affil-num=27 en-affil=Medical Genome Center, National Cerebral and Cardiovascular Center kn-affil= affil-num=28 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= affil-num=29 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=30 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= en-keyword=Brugada syndrome kn-keyword=Brugada syndrome en-keyword=SCN5A kn-keyword=SCN5A en-keyword=Lethal arrhythmia event kn-keyword=Lethal arrhythmia event en-keyword=Variant type kn-keyword=Variant type en-keyword=Loss of function kn-keyword=Loss of function END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=2 article-no= start-page=395 end-page=412.e6 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Maternal circadian rhythms during pregnancy dictate metabolic plasticity in offspring en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tissue-level oscillation is achieved by tissue-intrinsic clocks along with network-dependent signals originating from distal organs and organismal behavior. Yet, it remains unexplored whether maternal circadian rhythms during pregnancy influence fetal rhythms and impact long-term susceptibility to dietary challenges in offspring. Here, we demonstrate that circadian disruption during pregnancy decreased placental and neonatal weight yet retained transcriptional and structural maturation. Intriguingly, diet-induced obesity was exacerbated in parallel with arrhythmic feeding behavior, hypothalamic leptin resistance, and hepatic circadian reprogramming in offspring of chronodisrupted mothers. In utero circadian desynchrony altered the phase-relationship between the mother and fetus and impacted placental efficiency. Temporal feeding restriction in offspring failed to fully prevent obesity, whereas the circadian alignment of caloric restriction with the onset of the active phase virtually ameliorated the phenotype. Thus, maternal circadian rhythms during pregnancy confer adaptive properties to metabolic functions in offspring and provide insights into the developmental origins of health and disease. en-copyright= kn-copyright= en-aut-name=YaoNa en-aut-sei=Yao en-aut-mei=Na kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KinouchiKenichiro en-aut-sei=Kinouchi en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatohManami en-aut-sei=Katoh en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AshtianiKousha Changizi en-aut-sei=Ashtiani en-aut-mei=Kousha Changizi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AbdelkarimSherif en-aut-sei=Abdelkarim en-aut-mei=Sherif kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorimotoHiroyuki en-aut-sei=Morimoto en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TorimitsuTakuto en-aut-sei=Torimitsu en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KozumaTakahide en-aut-sei=Kozuma en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwaharaAkihide en-aut-sei=Iwahara en-aut-mei=Akihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KosugiShotaro en-aut-sei=Kosugi en-aut-mei=Shotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KomuroJin en-aut-sei=Komuro en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KatoKyosuke en-aut-sei=Kato en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=NakamuraToshifumi en-aut-sei=Nakamura en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ItohArata en-aut-sei=Itoh en-aut-mei=Arata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamaguchiShintaro en-aut-sei=Yamaguchi en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YoshinoJun en-aut-sei=Yoshino en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IrieJunichiro en-aut-sei=Irie en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HashimotoHisayuki en-aut-sei=Hashimoto en-aut-mei=Hisayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 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=20 ORCID= en-aut-name=SatohAkiko en-aut-sei=Satoh en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MikamiYohei en-aut-sei=Mikami en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=UchidaShusaku en-aut-sei=Uchida en-aut-mei=Shusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=UekiTakatoshi en-aut-sei=Ueki en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NomuraSeitaro en-aut-sei=Nomura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=BaldiPierre en-aut-sei=Baldi en-aut-mei=Pierre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=HayashiKaori en-aut-sei=Hayashi en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 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=28 ORCID= affil-num=1 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Computer Science, University of California kn-affil= affil-num=5 en-affil=Department of Computer Science, University of California kn-affil= affil-num=6 en-affil=Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=7 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=8 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=9 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=10 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=11 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=12 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=13 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=14 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=15 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=16 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=17 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=18 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=19 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=20 en-affil=Department of Cardiovascular Medicine, Academic Field, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=21 en-affil=Department of Integrative Physiology, Institute of Development, Aging and Cancer, Tohoku University kn-affil= affil-num=22 en-affil=Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=23 en-affil=Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=24 en-affil=Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=25 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=26 en-affil=Department of Computer Science, University of California kn-affil= affil-num=27 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=28 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= en-keyword=circadian rhythm kn-keyword=circadian rhythm en-keyword=metabolism kn-keyword=metabolism en-keyword=circadian clock kn-keyword=circadian clock en-keyword=pregnancy kn-keyword=pregnancy en-keyword=developmental origins of health and disease kn-keyword=developmental origins of health and disease en-keyword=obesity kn-keyword=obesity en-keyword=leptin kn-keyword=leptin en-keyword=time-restricted feeding kn-keyword=time-restricted feeding en-keyword=caloric restriction kn-keyword=caloric restriction en-keyword=eating behavior kn-keyword=eating behavior END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=7 article-no= start-page=002112 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) from the Animal dsRNA and ssRNA(?) Viruses Subcommittee, 2025 en-subtitle= kn-subtitle= en-abstract= kn-abstract=RNA viruses are ubiquitous in the environment and are important pathogens of humans, animals and plants. In 2024, the International Committee on Taxonomy of Viruses Animal dsRNA and ssRNA(?) Viruses Subcommittee submitted 18 taxonomic proposals for consideration. These proposals expanded the known virosphere by classifying 9 new genera and 88 species for newly detected virus genomes. Of note, newly established species expand the large family of Rhabdoviridae to 580 species. A new species in the family Arenaviridae includes a virus detected in Antarctic fish with a unique split nucleoprotein ORF. Additionally, four new species were established for historically isolated viruses with previously unsequenced genomes. Furthermore, three species were abolished due to incomplete genome sequence information, and one family was moved from being unassigned in the phylum Negarnaviricota into a subphylum and order. Herein, we summarize the 18 ratified taxonomic proposals and the general features of the current taxonomy, thereby supporting public and animal health responses. en-copyright= kn-copyright= en-aut-name=HughesHolly R. en-aut-sei=Hughes en-aut-mei=Holly R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BallingerMatthew J. en-aut-sei=Ballinger en-aut-mei=Matthew J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BaoYiming en-aut-sei=Bao en-aut-mei=Yiming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BejermanNicolas en-aut-sei=Bejerman en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BlasdellKim R. en-aut-sei=Blasdell en-aut-mei=Kim R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BrieseThomas en-aut-sei=Briese en-aut-mei=Thomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BrignoneJulia en-aut-sei=Brignone en-aut-mei=Julia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CarreraJean Paul en-aut-sei=Carrera en-aut-mei=Jean Paul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=De ConinckLander en-aut-sei=De Coninck en-aut-mei=Lander kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=de SouzaWilliam Marciel en-aut-sei=de Souza en-aut-mei=William Marciel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DebatHumberto en-aut-sei=Debat en-aut-mei=Humberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DietzgenRalf G. en-aut-sei=Dietzgen en-aut-mei=Ralf G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=D?rrwaldRalf en-aut-sei=D?rrwald en-aut-mei=Ralf kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ErdinMert en-aut-sei=Erdin en-aut-mei=Mert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FooksAnthony R. en-aut-sei=Fooks en-aut-mei=Anthony R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ForbesKristian M. en-aut-sei=Forbes en-aut-mei=Kristian M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Freitas-Ast?aJuliana en-aut-sei=Freitas-Ast?a en-aut-mei=Juliana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=GarciaJorge B. en-aut-sei=Garcia en-aut-mei=Jorge B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=GeogheganJemma L. en-aut-sei=Geoghegan en-aut-mei=Jemma L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=GrimwoodRebecca M. en-aut-sei=Grimwood en-aut-mei=Rebecca M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HorieMasayuki en-aut-sei=Horie en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HyndmanTimothy H. en-aut-sei=Hyndman en-aut-mei=Timothy H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=JohneReimar en-aut-sei=Johne en-aut-mei=Reimar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KlenaJohn D. en-aut-sei=Klena en-aut-mei=John D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KooninEugene V. en-aut-sei=Koonin en-aut-mei=Eugene V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KostygovAlexei Y. en-aut-sei=Kostygov en-aut-mei=Alexei Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=KrupovicMart en-aut-sei=Krupovic en-aut-mei=Mart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KuhnJens H. en-aut-sei=Kuhn en-aut-mei=Jens H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=LetkoMichael en-aut-sei=Letko en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=LiJun-Min en-aut-sei=Li en-aut-mei=Jun-Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=LiuYiyun en-aut-sei=Liu en-aut-mei=Yiyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=MartinMaria Laura en-aut-sei=Martin en-aut-mei=Maria Laura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=MullNathaniel en-aut-sei=Mull en-aut-mei=Nathaniel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=NazarYael en-aut-sei=Nazar en-aut-mei=Yael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=NowotnyNorbert en-aut-sei=Nowotny en-aut-mei=Norbert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=NunesM?rcio Roberto Teixeira en-aut-sei=Nunes en-aut-mei=M?rcio Roberto Teixeira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=?klandArnfinn Lodden en-aut-sei=?kland en-aut-mei=Arnfinn Lodden kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=RubbenstrothDennis en-aut-sei=Rubbenstroth en-aut-mei=Dennis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=RussellBrandy J. en-aut-sei=Russell en-aut-mei=Brandy J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=SchottEric en-aut-sei=Schott en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=SeifertStephanie en-aut-sei=Seifert en-aut-mei=Stephanie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=SenCarina en-aut-sei=Sen en-aut-mei=Carina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=ShedroffElizabeth en-aut-sei=Shedroff en-aut-mei=Elizabeth kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=SironenTarja en-aut-sei=Sironen en-aut-mei=Tarja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=SmuraTeemu en-aut-sei=Smura en-aut-mei=Teemu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=TavaresCamila Prestes Dos Santos en-aut-sei=Tavares en-aut-mei=Camila Prestes Dos Santos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=TeshRobert B. en-aut-sei=Tesh en-aut-mei=Robert B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=TilstonNatasha L. en-aut-sei=Tilston en-aut-mei=Natasha L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=TordoNo?l en-aut-sei=Tordo en-aut-mei=No?l kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=VasilakisNikos en-aut-sei=Vasilakis en-aut-mei=Nikos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=WalkerPeter J. en-aut-sei=Walker en-aut-mei=Peter J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 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=53 ORCID= en-aut-name=WhitfieldAnna E. en-aut-sei=Whitfield en-aut-mei=Anna E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=WhitmerShannon L.M. en-aut-sei=Whitmer en-aut-mei=Shannon L.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= en-aut-name=WolfYuri I. en-aut-sei=Wolf en-aut-mei=Yuri I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=56 ORCID= en-aut-name=XiaHan en-aut-sei=Xia en-aut-mei=Han kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=57 ORCID= en-aut-name=YeGong-Yin en-aut-sei=Ye en-aut-mei=Gong-Yin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=58 ORCID= en-aut-name=YeZhuangxin en-aut-sei=Ye en-aut-mei=Zhuangxin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=59 ORCID= en-aut-name=YurchenkoVyacheslav en-aut-sei=Yurchenko en-aut-mei=Vyacheslav kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=60 ORCID= en-aut-name=ZhaoMingli en-aut-sei=Zhao en-aut-mei=Mingli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=61 ORCID= affil-num=1 en-affil=Centers for Disease Control and Prevention kn-affil= affil-num=2 en-affil=Biological Sciences, Mississippi State University kn-affil= affil-num=3 en-affil=National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=Consejo Nacional de Investigaciones Cient?ficas y T?cnicas (CONICET) and Instituto Nacional de Tecnolog?a Agropecuaria (INTA) kn-affil= affil-num=5 en-affil=CSIRO Health and Biosecurity kn-affil= affil-num=6 en-affil=Center for Infection and Immunity, and Department of Epidemiology, Mailman School of Public Health, Columbia University kn-affil= affil-num=7 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=8 en-affil=Instituto Conmemorativo Gorgas de Estudios de la Salud kn-affil= affil-num=9 en-affil=Division of Clinical and Epidemiological Virology, KU Leuven kn-affil= affil-num=10 en-affil=Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky kn-affil= affil-num=11 en-affil=Instituto Nacional de Tecnolog?a Agropecuaria (INTA) kn-affil= affil-num=12 en-affil=QAAFI, The University of Queensland kn-affil= affil-num=13 en-affil=Robert Koch Institut kn-affil= affil-num=14 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=15 en-affil=Animal and Plant Health Agency (APHA) kn-affil= affil-num=16 en-affil=Department of Biological Sciences, University of Arkansas kn-affil= affil-num=17 en-affil=Embrapa Cassava and Fruits kn-affil= affil-num=18 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=19 en-affil=Department of Microbiology and Immunology, University of Otago kn-affil= affil-num=20 en-affil=Department of Microbiology and Immunology, University of Otago kn-affil= affil-num=21 en-affil=Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University kn-affil= affil-num=22 en-affil=School of Veterinary Medicine, Murdoch University kn-affil= affil-num=23 en-affil=German Federal Institute for Risk Assessment kn-affil= affil-num=24 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=25 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=26 en-affil=Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health kn-affil= affil-num=27 en-affil=University of Ostrava kn-affil= affil-num=28 en-affil=Institut Pasteur, Universit? Paris Cit?, CNRS UMR6047, Archaeal Virology Unit kn-affil= affil-num=29 en-affil=Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health kn-affil= affil-num=30 en-affil=Paul G. Allen School for Global Health, Washington State University kn-affil= affil-num=31 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=32 en-affil=National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences kn-affil= affil-num=33 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=34 en-affil=Department of Natural Sciences, Shawnee State University kn-affil= affil-num=35 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=36 en-affil=College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health kn-affil= affil-num=37 en-affil=Universidade Federal do Par? kn-affil= affil-num=38 en-affil=Pharmaq Analytiq kn-affil= affil-num=39 en-affil=Institute of Diagnostic Virology, Friedrich-Loeffler-Institut kn-affil= affil-num=40 en-affil=Centers for Disease Control and Prevention kn-affil= affil-num=41 en-affil=Institute of Marine and Environmental Technology, University of Maryland Center for Environmental Science kn-affil= affil-num=42 en-affil=Paul G. Allen School for Global Health, Washington State University kn-affil= affil-num=43 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=44 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=45 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=46 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=47 en-affil=Integrated Group of Aquaculture and Environmental Studies, Federal University of Paran? kn-affil= affil-num=48 en-affil=Department of Pathology, The University of Texas Medical Branch kn-affil= affil-num=49 en-affil=Department of Microbiology and Immunology, Indiana University School of Medicine kn-affil= affil-num=50 en-affil=Institut Pasteur kn-affil= affil-num=51 en-affil=Department of Pathology, The University of Texas Medical Branch kn-affil= affil-num=52 en-affil=University of Queensland kn-affil= affil-num=53 en-affil=Wuhan Institute of Virology, Chinese Academy of Sciences kn-affil= affil-num=54 en-affil=North Carolina State University kn-affil= affil-num=55 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=56 en-affil=Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health kn-affil= affil-num=57 en-affil=Wuhan Institute of Virology, Chinese Academy of Sciences kn-affil= affil-num=58 en-affil=Institute of Insect Sciences, Zhejiang University kn-affil= affil-num=59 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=60 en-affil=University of Ostrava kn-affil= affil-num=61 en-affil=Department of Pathobiology and Population Sciences, Royal Veterinary College kn-affil= END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=7 article-no= start-page=002114 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses from the Plant Viruses Subcommittee, 2025 en-subtitle= kn-subtitle= en-abstract= kn-abstract=In March 2025, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote, newly proposed taxa were added to those under the mandate of the Plant Viruses Subcommittee. In brief, 1 new order, 3 new families, 6 new genera, 2 new subgenera and 206 new species were created. Some taxa were reorganized. Genus Cytorhabdovirus in the family Rhabdoviridae was abolished and its taxa were redistributed into three new genera Alphacytorhabdovirus, Betacytorhabdovirus and Gammacytorhabdovirus. Genus Waikavirus in the family Secoviridae was reorganized into two subgenera (Actinidivirus and Ritunrivirus). One family and four previously unaffiliated genera were moved to the newly established order Tombendovirales. Twelve species not assigned to a genus were abolished. To comply with the ICTV mandate of a binomial format for virus species, eight species were renamed. Demarcation criteria in the absence of biological information were defined in the genus Ilarvirus (family Bromoviridae). This article presents the updated taxonomy put forth by the Plant Viruses Subcommittee and ratified by the ICTV. en-copyright= kn-copyright= en-aut-name=RubinoLuisa en-aut-sei=Rubino en-aut-mei=Luisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AbrahamianPeter en-aut-sei=Abrahamian en-aut-mei=Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AnWenxia en-aut-sei=An en-aut-mei=Wenxia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArandaMiguel A. en-aut-sei=Aranda en-aut-mei=Miguel A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Ascencio-Iba?ezJos? T. en-aut-sei=Ascencio-Iba?ez en-aut-mei=Jos? T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BejermanNicolas en-aut-sei=Bejerman en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BlouinArnaud G. en-aut-sei=Blouin en-aut-mei=Arnaud G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CandresseThierry en-aut-sei=Candresse en-aut-mei=Thierry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=CantoTomas en-aut-sei=Canto en-aut-mei=Tomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=CaoMengji en-aut-sei=Cao en-aut-mei=Mengji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=CarrJohn P. en-aut-sei=Carr en-aut-mei=John P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ChoWon Kyong en-aut-sei=Cho en-aut-mei=Won Kyong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ConstableFiona en-aut-sei=Constable en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=DasguptaIndranil en-aut-sei=Dasgupta en-aut-mei=Indranil kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=DebatHumberto en-aut-sei=Debat en-aut-mei=Humberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=DietzgenRalf G. en-aut-sei=Dietzgen en-aut-mei=Ralf G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=DigiaroMichele en-aut-sei=Digiaro en-aut-mei=Michele kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=DonaireLivia en-aut-sei=Donaire en-aut-mei=Livia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ElbeainoToufic en-aut-sei=Elbeaino en-aut-mei=Toufic kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FargetteDenis en-aut-sei=Fargette en-aut-mei=Denis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=FilardoFiona en-aut-sei=Filardo en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=FischerMatthias G. en-aut-sei=Fischer en-aut-mei=Matthias G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FontdevilaNuria en-aut-sei=Fontdevila en-aut-mei=Nuria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=FoxAdrian en-aut-sei=Fox en-aut-mei=Adrian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=Freitas-AstuaJuliana en-aut-sei=Freitas-Astua en-aut-mei=Juliana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=FuchsMarc en-aut-sei=Fuchs en-aut-mei=Marc kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=GeeringAndrew D.W. en-aut-sei=Geering en-aut-mei=Andrew D.W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=GhafariMahan en-aut-sei=Ghafari en-aut-mei=Mahan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=Hafr?nAnders en-aut-sei=Hafr?n en-aut-mei=Anders kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=HammondJohn en-aut-sei=Hammond en-aut-mei=John kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=HammondRosemarie en-aut-sei=Hammond en-aut-mei=Rosemarie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=Hasi?w-JaroszewskaBeata en-aut-sei=Hasi?w-Jaroszewska en-aut-mei=Beata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=HebrardEugenie en-aut-sei=Hebrard en-aut-mei=Eugenie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=Hern?ndezCarmen en-aut-sei=Hern?ndez en-aut-mei=Carmen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=HilyJean-Michel en-aut-sei=Hily en-aut-mei=Jean-Michel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=HosseiniAhmed en-aut-sei=Hosseini en-aut-mei=Ahmed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=HullRoger en-aut-sei=Hull en-aut-mei=Roger kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=Inoue-NagataAlice K. en-aut-sei=Inoue-Nagata en-aut-mei=Alice K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=JordanRamon en-aut-sei=Jordan en-aut-mei=Ramon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=KreuzeJan F. en-aut-sei=Kreuze en-aut-mei=Jan F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=KrupovicMart en-aut-sei=Krupovic en-aut-mei=Mart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=KubotaKenji en-aut-sei=Kubota en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=KuhnJens H. en-aut-sei=Kuhn en-aut-mei=Jens H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=LeisnerScott en-aut-sei=Leisner en-aut-mei=Scott kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=LettJean-Michel en-aut-sei=Lett en-aut-mei=Jean-Michel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=LiChengyu en-aut-sei=Li en-aut-mei=Chengyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=LiFan en-aut-sei=Li en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=LiJun Min en-aut-sei=Li en-aut-mei=Jun Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=L?pez-LambertiniPaola M. en-aut-sei=L?pez-Lambertini en-aut-mei=Paola M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=Lopez-MoyaJuan J. en-aut-sei=Lopez-Moya en-aut-mei=Juan J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=MaclotFrancois en-aut-sei=Maclot en-aut-mei=Francois kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=M?kinenKristiina en-aut-sei=M?kinen en-aut-mei=Kristiina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=MartinDarren en-aut-sei=Martin en-aut-mei=Darren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=MassartSebastien en-aut-sei=Massart en-aut-mei=Sebastien kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= en-aut-name=MillerW. Allen en-aut-sei=Miller en-aut-mei=W. Allen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=56 ORCID= en-aut-name=MohammadiMusa en-aut-sei=Mohammadi en-aut-mei=Musa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=57 ORCID= en-aut-name=MollovDimitre en-aut-sei=Mollov en-aut-mei=Dimitre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=58 ORCID= en-aut-name=MullerEmmanuelle en-aut-sei=Muller en-aut-mei=Emmanuelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=59 ORCID= en-aut-name=NagataTatsuya en-aut-sei=Nagata en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=60 ORCID= en-aut-name=Navas-CastilloJes?s en-aut-sei=Navas-Castillo en-aut-mei=Jes?s kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=61 ORCID= en-aut-name=NeriyaYutaro en-aut-sei=Neriya en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=62 ORCID= en-aut-name=Ochoa-CoronaFrancisco M. en-aut-sei=Ochoa-Corona en-aut-mei=Francisco M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=63 ORCID= en-aut-name=OhshimaKazusato en-aut-sei=Ohshima en-aut-mei=Kazusato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=64 ORCID= en-aut-name=Pall?sVicente en-aut-sei=Pall?s en-aut-mei=Vicente kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=65 ORCID= en-aut-name=PappuHanu en-aut-sei=Pappu en-aut-mei=Hanu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=66 ORCID= en-aut-name=PetrzikKarel en-aut-sei=Petrzik en-aut-mei=Karel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=67 ORCID= en-aut-name=PoogginMikhail en-aut-sei=Pooggin en-aut-mei=Mikhail kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=68 ORCID= en-aut-name=PrigigalloMaria Isabella en-aut-sei=Prigigallo en-aut-mei=Maria Isabella kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=69 ORCID= en-aut-name=Ramos-Gonz?lezPedro L. en-aut-sei=Ramos-Gonz?lez en-aut-mei=Pedro L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=70 ORCID= en-aut-name=RibeiroSimone en-aut-sei=Ribeiro en-aut-mei=Simone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=71 ORCID= en-aut-name=Richert-P?ggelerKatja R. en-aut-sei=Richert-P?ggeler en-aut-mei=Katja R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=72 ORCID= en-aut-name=RoumagnacPhilippe en-aut-sei=Roumagnac en-aut-mei=Philippe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=73 ORCID= en-aut-name=RoyAvijit en-aut-sei=Roy en-aut-mei=Avijit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=74 ORCID= en-aut-name=SabanadzovicSead en-aut-sei=Sabanadzovic en-aut-mei=Sead kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=75 ORCID= en-aut-name=?af??ov?Dana en-aut-sei=?af??ov? en-aut-mei=Dana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=76 ORCID= en-aut-name=SaldarelliPasquale en-aut-sei=Saldarelli en-aut-mei=Pasquale kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=77 ORCID= en-aut-name=Sanfa?onH?l?ne en-aut-sei=Sanfa?on en-aut-mei=H?l?ne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=78 ORCID= en-aut-name=SarmientoCecilia en-aut-sei=Sarmiento en-aut-mei=Cecilia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=79 ORCID= en-aut-name=SasayaTakahide en-aut-sei=Sasaya en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=80 ORCID= en-aut-name=ScheetsKay en-aut-sei=Scheets en-aut-mei=Kay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=81 ORCID= en-aut-name=SchravesandeWillem E.W. en-aut-sei=Schravesande en-aut-mei=Willem E.W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=82 ORCID= en-aut-name=SealSusan en-aut-sei=Seal en-aut-mei=Susan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=83 ORCID= en-aut-name=ShimomotoYoshifumi en-aut-sei=Shimomoto en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=84 ORCID= en-aut-name=S?meraMerike en-aut-sei=S?mera en-aut-mei=Merike kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=85 ORCID= en-aut-name=StavoloneLivia en-aut-sei=Stavolone en-aut-mei=Livia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=86 ORCID= en-aut-name=StewartLucy R. en-aut-sei=Stewart en-aut-mei=Lucy R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=87 ORCID= en-aut-name=TeycheneyPierre-Yves en-aut-sei=Teycheney en-aut-mei=Pierre-Yves kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=88 ORCID= en-aut-name=ThomasJohn E. en-aut-sei=Thomas en-aut-mei=John E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=89 ORCID= en-aut-name=ThompsonJeremy R. en-aut-sei=Thompson en-aut-mei=Jeremy R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=90 ORCID= en-aut-name=TiberiniAntonio en-aut-sei=Tiberini en-aut-mei=Antonio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=91 ORCID= en-aut-name=TomitakaYasuhiro en-aut-sei=Tomitaka en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=92 ORCID= en-aut-name=TzanetakisIoannis en-aut-sei=Tzanetakis en-aut-mei=Ioannis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=93 ORCID= en-aut-name=UmberMarie en-aut-sei=Umber en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=94 ORCID= en-aut-name=UrbinoCica en-aut-sei=Urbino en-aut-mei=Cica kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=95 ORCID= en-aut-name=van den BurgHarrold A. en-aut-sei=van den Burg en-aut-mei=Harrold A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=96 ORCID= en-aut-name=Van der VlugtRen? A.A. en-aut-sei=Van der Vlugt en-aut-mei=Ren? A.A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=97 ORCID= en-aut-name=VarsaniArvind en-aut-sei=Varsani en-aut-mei=Arvind kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=98 ORCID= en-aut-name=VerhageAdriaan en-aut-sei=Verhage en-aut-mei=Adriaan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=99 ORCID= en-aut-name=VillamorDan en-aut-sei=Villamor en-aut-mei=Dan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=100 ORCID= en-aut-name=von BargenSusanne en-aut-sei=von Bargen en-aut-mei=Susanne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=101 ORCID= en-aut-name=WalkerPeter J. en-aut-sei=Walker en-aut-mei=Peter J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=102 ORCID= en-aut-name=WetzelThierry en-aut-sei=Wetzel en-aut-mei=Thierry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=103 ORCID= en-aut-name=WhitfieldAnna E. en-aut-sei=Whitfield en-aut-mei=Anna E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=104 ORCID= en-aut-name=WylieStephen J. en-aut-sei=Wylie en-aut-mei=Stephen J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=105 ORCID= en-aut-name=YangCaixia en-aut-sei=Yang en-aut-mei=Caixia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=106 ORCID= en-aut-name=ZerbiniF. Murilo en-aut-sei=Zerbini en-aut-mei=F. Murilo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=107 ORCID= en-aut-name=ZhangSong en-aut-sei=Zhang en-aut-mei=Song kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=108 ORCID= affil-num=1 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=2 en-affil=USDA-ARS, BARC, National Germplasm Resources Laboratory kn-affil= affil-num=3 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=4 en-affil=Centro de Edafolog?a y Biolog?a Aplicada del Segura-CSIC kn-affil= affil-num=5 en-affil=Department of Molecular and Structural Biochemistry, North Carolina State University kn-affil= affil-num=6 en-affil=Unidad de Fitopatolog?a y Modelizaci?n Agr?cola (UFYMA) INTA-CONICET kn-affil= affil-num=7 en-affil=Plant Protection Department kn-affil= affil-num=8 en-affil=UMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAE kn-affil= affil-num=9 en-affil=Margarita Salas Center for Biological Research (CIB-CSIC) Spanish Council for Scientific Research (CSIC) kn-affil= affil-num=10 en-affil=National Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest University kn-affil= affil-num=11 en-affil=Department of Plant Sciences, University of Cambridge kn-affil= affil-num=12 en-affil=Agriculture and Life Sciences Research Institute, Kangwon National University kn-affil= affil-num=13 en-affil=Agriculture Victoria Research, Department of Energy, Environment and Climate Action and School of Applied Systems Biology, La Trobe University kn-affil= affil-num=14 en-affil=University of Delhi South Campu kn-affil= affil-num=15 en-affil=Unidad de Fitopatolog?a y Modelizaci?n Agr?cola (UFYMA) INTA-CONICET kn-affil= affil-num=16 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=17 en-affil=CIHEAM, Istituto Agronomico Mediterraneo of Bari kn-affil= affil-num=18 en-affil=Centro de Edafolog?a y Biolog?a Aplicada del Segura-CSIC kn-affil= affil-num=19 en-affil=CIHEAM, Istituto Agronomico Mediterraneo of Bari kn-affil= affil-num=20 en-affil=Virus South Data kn-affil= affil-num=21 en-affil=Queensland Department of Primary Industries kn-affil= affil-num=22 en-affil=Max Planck Institute for Marine Microbiology kn-affil= affil-num=23 en-affil=Plant Protection Department kn-affil= affil-num=24 en-affil=Fera Science Ltd (Fera), York Biotech Campus kn-affil= affil-num=25 en-affil=Embrapa Cassava and Fruits, Brazilian Agricultural Research Corporation kn-affil= affil-num=26 en-affil=Plant Pathology, Cornell University kn-affil= affil-num=27 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=28 en-affil=Department of Biology, University of Oxford kn-affil= affil-num=29 en-affil=Swedish University of Agriculture kn-affil= affil-num=30 en-affil=USDA-ARS, USNA, Floral and Nursery Plants Research Unit kn-affil= affil-num=31 en-affil=USDA-ARS, BARC, Molecular Plant Pathology Laboratory kn-affil= affil-num=32 en-affil=Institute of Plant Protection-NRI kn-affil= affil-num=33 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro kn-affil= affil-num=34 en-affil=Instituto de Biolog?a Molecular y Celular de Plantas (IBMCP), Universitat Polit?cnica de Valencia-CSIC kn-affil= affil-num=35 en-affil=Institut Fran?ais de la Vigne et du Vin kn-affil= affil-num=36 en-affil=Vali-e-Asr University of Rafsanjan, Department of Plant Protection kn-affil= affil-num=37 en-affil=Retired from John Innes Centre kn-affil= affil-num=38 en-affil=Embrapa Hortali?as kn-affil= affil-num=39 en-affil=USDA-ARS, USNA, Floral and Nursery Plants Research Unit kn-affil= affil-num=40 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=41 en-affil=International Potato Center (CIP) kn-affil= affil-num=42 en-affil=Institut Pasteur, Universit? Paris Cit?, CNRS UMR6047, Archaeal Virology Unit kn-affil= affil-num=43 en-affil=Institute for Plant Protection, NARO kn-affil= affil-num=44 en-affil=Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health kn-affil= affil-num=45 en-affil=Department of Biological Sciences, University of Toledo kn-affil= affil-num=46 en-affil=CIRAD, UMR PVBMT kn-affil= affil-num=47 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=48 en-affil=State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University kn-affil= affil-num=49 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=50 en-affil=Instituto de Patolog?a Vegetal (IPAVE), INTA, Unidad de Fitopatolog?a y Modelizaci?n Agr?cola (UFYMA) INTA-CONICET kn-affil= affil-num=51 en-affil=Centre for Research in Agricultural Genomics, CRAG (CSIC-IRTA-UAB-UB) kn-affil= affil-num=52 en-affil=UMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAE kn-affil= affil-num=53 en-affil=Department of Agricultural Sciences, University of Helsinki kn-affil= affil-num=54 en-affil=Institute of Infectious Disease and Molecular Medicine, University of Cape Town kn-affil= affil-num=55 en-affil=Plant Pathology Laboratory, TERRA Gembloux Agro-Bio Tech, University of Liege kn-affil= affil-num=56 en-affil=Department of Plant Pathology, Entomology and Microbiology, Iowa State University kn-affil= affil-num=57 en-affil=Department of Plant Protection, Gorgan University of Agricultural Sciences and Natural Resources kn-affil= affil-num=58 en-affil=USDA-APHIS, Plant Protection and Quarantine kn-affil= affil-num=59 en-affil=CIRAD, AGAP Institut; AGAP Institut, University of Montpellier; CIRAD, INRAE kn-affil= affil-num=60 en-affil=Instituto de Ci?ncias Biol?gicas, Universidade de Bras?lia kn-affil= affil-num=61 en-affil=Instituto de Hortofruticultura Subtropical y Mediterr?nea “La Mayora” (IHSM-UMA-CSIC), Consejo Superior de Investigaciones Cient?ficas kn-affil= affil-num=62 en-affil=Utsunomiya University kn-affil= affil-num=63 en-affil=Oklahoma State University, Institute for Biosecurity & Microbial Forensics kn-affil= affil-num=64 en-affil=Saga University kn-affil= affil-num=65 en-affil=Instituto de Biolog?a Molecular y Celular de Plantas (IBMCP), Universitat Polit?cnica de Valencia-CSIC kn-affil= affil-num=66 en-affil=Department of Plant Pathology, Washington State University kn-affil= affil-num=67 en-affil=Institute of Plant Molecular Biology kn-affil= affil-num=68 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD kn-affil= affil-num=69 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=70 en-affil=Applied Molecular Biology Laboratory, Instituto Biol?gico de S?o Paulo kn-affil= affil-num=71 en-affil=Embrapa Recursos Gen?ticos e Biotecnologia kn-affil= affil-num=72 en-affil=Julius K?hn Institute, Federal Research Centre for Cultivated Plants, Institute for Epidemiology and Pathogen Diagnostics kn-affil= affil-num=73 en-affil=CIRAD, UMR PHIM kn-affil= affil-num=74 en-affil=USDA-ARS, BARC, Molecular Plant Pathology Laboratory, Beltsville, MD, USA kn-affil= affil-num=75 en-affil=Department of Agricultural Science and Plant Protection, Mississippi State University kn-affil= affil-num=76 en-affil=Department of Cell Biology and Genetics, Faculty of Science, Palack? University Olomouc kn-affil= affil-num=77 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=78 en-affil=Summerland Research and Development Centre, Agriculture and Agri-Food Canada kn-affil= affil-num=79 en-affil=Department of Chemistry and Biotechnology, Tallinn University of Technology kn-affil= affil-num=80 en-affil=Strategic Planning Headquarters, NARO kn-affil= affil-num=81 en-affil=Department of Plant Pathology, Ecology and Evolution, Oklahoma State University kn-affil= affil-num=82 en-affil=Molecular Plant Pathology, University of Amsterdam kn-affil= affil-num=83 en-affil=Natural Resources Institute, University of Greenwich kn-affil= affil-num=84 en-affil=Kochi Agricultural Research Center kn-affil= affil-num=85 en-affil=Department of Chemistry and Biotechnology, Tallinn University of Technology kn-affil= affil-num=86 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=87 en-affil=Currently unaffiliated kn-affil= affil-num=88 en-affil=CIRAD, UMR PVBMT & UMR PVBMT, Universit? de la R?union kn-affil= affil-num=89 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=90 en-affil=Plant Health and Environment Laboratory kn-affil= affil-num=91 en-affil=Council for Agricultural Research and Economics, Research Centre for Plant Protection and Certification kn-affil= affil-num=92 en-affil=Institute for Plant Protection, NARO kn-affil= affil-num=93 en-affil=Department of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas System kn-affil= affil-num=94 en-affil=INRAE, UR ASTRO kn-affil= affil-num=95 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro kn-affil= affil-num=96 en-affil=Molecular Plant Pathology, University of Amsterdam kn-affil= affil-num=97 en-affil=Wageningen University and Research kn-affil= affil-num=98 en-affil=The Biodesign Center for Fundamental and Applied Microbiomics, Center for Evolution and Medicine, School of Life Sciences, Arizona State University kn-affil= affil-num=99 en-affil=Rijk Zwaan Breeding B.V. kn-affil= affil-num=100 en-affil=Department of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas System kn-affil= affil-num=101 en-affil=Humboldt-Universit?t zu Berlin, Thaer-Institute of Agricultural and Horticultural Sciences kn-affil= affil-num=102 en-affil=The University of Queensland kn-affil= affil-num=103 en-affil=Dienstleistungszentrum L?ndlicher Raum Rheinpfalz kn-affil= affil-num=104 en-affil=North Carolina State University kn-affil= affil-num=105 en-affil=Food Futures Institute, Murdoch University kn-affil= affil-num=106 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=107 en-affil=Dep. de Fitopatologia/BIOAGRO, Universidade Federal de Vi?osa kn-affil= affil-num=108 en-affil=National Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=12 article-no= start-page=2429 end-page=2437 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Discovery of a Compound That Inhibits IRE1α S-Nitrosylation and Preserves the Endoplasmic Reticulum Stress Response under Nitrosative Stress en-subtitle= kn-subtitle= en-abstract= kn-abstract=Inositol-requiring enzyme 1α (IRE1α) is a sensor of endoplasmic reticulum (ER) stress and drives ER stress response pathways. Activated IRE1α exhibits RNase activity and cleaves mRNA encoding X-box binding protein 1, a transcription factor that induces the expression of genes that maintain ER proteostasis for cell survival. Previously, we showed that IRE1α undergoes S-nitrosylation, a post-translational modification induced by nitric oxide (NO), resulting in reduced RNase activity. Therefore, S-nitrosylation of IRE1α compromises the response to ER stress, making cells more vulnerable. We conducted virtual screening and cell-based validation experiments to identify compounds that inhibit the S-nitrosylation of IRE1α by targeting nitrosylated cysteine residues. We ultimately identified a compound (1ACTA) that selectively inhibits the S-nitrosylation of IRE1α and prevents the NO-induced reduction of RNase activity. Furthermore, 1ACTA reduces the rate of NO-induced cell death. Our research identified S-nitrosylation as a novel target for drug development for IRE1α and provides a suitable screening strategy. en-copyright= kn-copyright= en-aut-name=KurogiHaruna en-aut-sei=Kurogi en-aut-mei=Haruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=KumarAshutosh en-aut-sei=Kumar en-aut-mei=Ashutosh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiTakehiro en-aut-sei=Suzuki en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DohmaeNaoshi en-aut-sei=Dohmae en-aut-mei=Naoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SawadaDaisuke en-aut-sei=Sawada en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ZhangKam Y.J. en-aut-sei=Zhang en-aut-mei=Kam Y.J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of 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=Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN kn-affil= affil-num=5 en-affil=Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=6 en-affil=Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=7 en-affil=Department of Fine Organic Synthesis, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN kn-affil= affil-num=9 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue=1 article-no= start-page=e70040 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=Avoidant/restrictive food intake disorder prognosis and its relation with autism spectrum disorder in Japanese children en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: There is a lack of reported clinical factors associated with the outcomes of children and adolescents with avoidant/restrictive food intake disorder (ARFID) in Japan. This study aimed to identify these clinical factors and explore the relationship between ARFID and autism spectrum disorder (ASD).
Methods: This retrospective study analyzed data from 48 Japanese children and adolescents with ARFID who visited Okayama University Hospital between January 2011 and March 2022. Clinical characteristics were assessed using medical records and natural history questionnaires. The study compared patients with good and poor prognosis groups and used multiple logistic regression analysis to determine factors influencing prognosis.
Results: The study included 33 patients with good prognoses and 15 with poor prognoses. Comorbid ASD was more prevalent in the poor prognosis group (60%) compared to the good prognosis group (21%). Additionally, more than half of the ARFID patients with comorbid ASD were initially undiagnosed. Multivariate analysis revealed that older age at first visit (p?=?0.022) and comorbid ASD (p?=?0.022) were statistically significant factors associated with poor prognosis in ARFID patients. There were no significant differences in body mass index standard deviation score and maximal weight loss between the two groups.
Conclusions: The poor prognosis group had a higher prevalence of comorbid ASD diagnoses. Therefore, it is crucial to evaluate patient's developmental characteristics early in treatment and consider these characteristics throughout the course of care. en-copyright= kn-copyright= en-aut-name=TanakaChie en-aut-sei=Tanaka en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkadaAyumi en-aut-sei=Okada en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HanzawaMana en-aut-sei=Hanzawa en-aut-mei=Mana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiChikako en-aut-sei=Fujii en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShigeyasuYoshie en-aut-sei=Shigeyasu en-aut-mei=Yoshie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugiharaAkiko en-aut-sei=Sugihara en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HoriuchiMakiko en-aut-sei=Horiuchi en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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 Pediatrics, 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 Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Clinical Psychology Section, Department of Medical Support, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=autism spectrum disorder kn-keyword=autism spectrum disorder en-keyword=avoidant/restrictive food intake disorder kn-keyword=avoidant/restrictive food intake disorder en-keyword=children kn-keyword=children en-keyword=feeding and eating disorders kn-keyword=feeding and eating disorders en-keyword=outcome kn-keyword=outcome END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=551 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240827 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Body weight and eating attitudes influence improvement of depressive symptoms in children and pre-adolescents with eating disorders: a prospective multicenter cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Pediatric patients with eating disorders in a multicenter joint study on 11 facilities were enrolled and prospectively investigated to determine whether improvement in body weight, eating attitudes, and psychosocial factors in children with eating disorders would also improve depressive symptoms.
Methods In this study, 91 patients were enrolled between April 2014 and March 2016. The severity of underweight was assessed using the body mass index-standard deviation score (BMI-SDS), eating behavior was assessed using the children's eating attitude test (ChEAT26), the outcome of childhood eating disorders was assessed using the childhood eating disorder outcome scale, and depressive symptoms were assessed using the Children's Depression Inventory (CDI) score.
Results After 12 months of treatment, depressive symptoms were evaluated in 62 of the 91 cases where it was evaluated at the initial phase. There was no difference in background characteristics between the included patients and the 29 patients who dropped out. A paired-sample t-test revealed a significant decrease in CDI scores after 12 months of treatment (p? Conclusions Depressive symptoms in children with eating disorders improved with therapeutic intervention on body weight and eating attitudes.
Trial registration The Clinical Trial Number for this study is UMIN000055004. en-copyright= kn-copyright= en-aut-name=SuzukiYuichi en-aut-sei=Suzuki en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagamitsuShinichiro en-aut-sei=Nagamitsu en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EshimaNobuoki en-aut-sei=Eshima en-aut-mei=Nobuoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueTakeshi en-aut-sei=Inoue en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtaniRyoko en-aut-sei=Otani en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakutaRyoichi en-aut-sei=Sakuta en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IguchiToshiyuki en-aut-sei=Iguchi en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshiiRyuta en-aut-sei=Ishii en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchidaSoh en-aut-sei=Uchida en-aut-mei=Soh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkadaAyumi en-aut-sei=Okada en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KitayamaShinji en-aut-sei=Kitayama en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KoyanagiKenshi en-aut-sei=Koyanagi en-aut-mei=Kenshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SuzukiYuki en-aut-sei=Suzuki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SumiYoshino en-aut-sei=Sumi en-aut-mei=Yoshino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakamiyaShizuo en-aut-sei=Takamiya en-aut-mei=Shizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiiChikako en-aut-sei=Fujii en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FukaiYoshimitsu en-aut-sei=Fukai en-aut-mei=Yoshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Pediatrics, Fukushima Medical University School of Medicine kn-affil= affil-num=2 en-affil=Department of Pediatrics, Fukuoka University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Pediatrics, Kurume University School of Medicine kn-affil= affil-num=4 en-affil=Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center kn-affil= affil-num=5 en-affil=Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center kn-affil= affil-num=6 en-affil=Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center kn-affil= affil-num=7 en-affil=Department of Pediatrics, Hoshigaoka Maternity Hospital kn-affil= affil-num=8 en-affil=Department of Pediatrics and Child Health, Kurume University School of Medicine kn-affil= affil-num=9 en-affil=Karamun`S Forest Children`S Clinic kn-affil= affil-num=10 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Himeji City Center for the Disabled kn-affil= affil-num=12 en-affil=Nagasaki Prefectural Center of Medicine and Welfare for Children kn-affil= affil-num=13 en-affil=Department of Pediatrics, National Hospital Organization Mie National Hospital kn-affil= affil-num=14 en-affil=Mental and Developmental Clinic for Children “Elm Tree” kn-affil= affil-num=15 en-affil=Takamiya Psychiatry Clinic kn-affil= affil-num=16 en-affil=Department of Pediatrics/Child Psychosomatic Medicine, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Pediatrics, St. Luke’s International Hospital kn-affil= en-keyword=Eating disorders kn-keyword=Eating disorders en-keyword=Anorexia nervosa kn-keyword=Anorexia nervosa en-keyword=Body mass index-standard deviation score kn-keyword=Body mass index-standard deviation score en-keyword=Eating attitudes kn-keyword=Eating attitudes en-keyword=Children’s depression inventory kn-keyword=Children’s depression inventory END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=6 article-no= start-page=466 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250617 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Artificial Intelligence Approach in Machine Learning-Based Modeling and Networking of the Coronavirus Pathogenesis Pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=The coronavirus pathogenesis pathway, which consists of severe acute respiratory syndrome (SARS) coronavirus infection and signaling pathways, including the interferon pathway, the transforming growth factor beta pathway, the mitogen-activated protein kinase pathway, the apoptosis pathway, and the inflammation pathway, is activated upon coronaviral infection. An artificial intelligence approach based on machine learning was utilized to develop models with images of the coronavirus pathogenesis pathway to predict the activation states. Data on coronaviral infection held in a database were analyzed with Ingenuity Pathway Analysis (IPA), a network pathway analysis tool. Data related to SARS coronavirus 2 (SARS-CoV-2) were extracted from more than 100,000 analyses and datasets in the IPA database. A total of 27 analyses, including nine analyses of SARS-CoV-2-infected human-induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes and fibroblasts, and a total of 22 analyses of SARS-CoV-2-infected lung adenocarcinoma (LUAD), were identified as being related to “human” and “SARS coronavirus 2” in the database. The coronavirus pathogenesis pathway was activated in SARS-CoV-2-infected iPSC-derived cells and LUAD cells. A prediction model was developed in Python 3.11 using images of the coronavirus pathogenesis pathway under different conditions. The prediction model of activation states of the coronavirus pathogenesis pathway may aid in treatment identification. en-copyright= kn-copyright= en-aut-name=TanabeShihori en-aut-sei=Tanabe en-aut-mei=Shihori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=QuaderSabina en-aut-sei=Quader en-aut-mei=Sabina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnoRyuichi en-aut-sei=Ono en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaHiroyoshi Y. en-aut-sei=Tanaka en-aut-mei=Hiroyoshi Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoAkihisa en-aut-sei=Yamamoto en-aut-mei=Akihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KojimaMotohiro en-aut-sei=Kojima en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PerkinsEdward J. en-aut-sei=Perkins en-aut-mei=Edward J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CabralHoracio en-aut-sei=Cabral en-aut-mei=Horacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=2 en-affil=Innovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion kn-affil= affil-num=3 en-affil=Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=4 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Mechanical Systems Engineering, Graduate School of Systems Design Tokyo Metropolitan University kn-affil= affil-num=6 en-affil=Department of Surgical Pathology, Kyoto Prefecture University of Medicine kn-affil= affil-num=7 en-affil=US Army Engineer Research and Development Center kn-affil= affil-num=8 en-affil=Department of Bioengineering, Graduate School of Engineering, The University of Tokyo kn-affil= en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=coronavirus kn-keyword=coronavirus en-keyword=coronaviral infection kn-keyword=coronaviral infection en-keyword=machine learning kn-keyword=machine learning en-keyword=pathway analysis kn-keyword=pathway analysis en-keyword=predictionmodel kn-keyword=predictionmodel en-keyword=molecular network kn-keyword=molecular network en-keyword=molecular pathway image kn-keyword=molecular pathway image en-keyword=network analysis kn-keyword=network analysis END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=11 article-no= start-page=4984 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Induced Pluripotent Stem Cells in Cardiomyopathy: Advancing Disease Modeling, Therapeutic Development, and Regenerative Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cardiomyopathies are a heterogeneous group of heart muscle diseases that can lead to heart failure, arrhythmias, and sudden cardiac death. Traditional animal models and in vitro systems have limitations in replicating the complex pathology of human cardiomyopathies. Induced pluripotent stem cells (iPSCs) offer a transformative platform by enabling the generation of patient-specific cardiomyocytes, thus opening new avenues for disease modeling, drug discovery, and regenerative therapy. This process involves reprogramming somatic cells into iPSCs and subsequently differentiating them into functional cardiomyocytes, which can be characterized using techniques such as electrophysiology, contractility assays, and gene expression profiling. iPSC-derived cardiomyocyte (iPSC-CM) platforms are also being explored for drug screening and personalized medicine, including high-throughput testing for cardiotoxicity and the identification of patient-tailored therapies. While iPSC-CMs already serve as valuable models for understanding disease mechanisms and screening drugs, ongoing advances in maturation and bioengineering are bringing iPSC-based therapies closer to clinical application. Furthermore, the integration of multi-omics approaches and artificial intelligence (AI) is enhancing the predictive power of iPSC models. iPSC-based technologies are paving the way for a new era of personalized cardiology, with the potential to revolutionize the management of cardiomyopathies through patient-specific insights and regenerative strategies. en-copyright= kn-copyright= en-aut-name=VoQuan Duy en-aut-sei=Vo en-aut-mei=Quan Duy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=induced pluripotent stem cells kn-keyword=induced pluripotent stem cells en-keyword=cardiomyopathy kn-keyword=cardiomyopathy en-keyword=disease modeling kn-keyword=disease modeling en-keyword=drug screening kn-keyword=drug screening en-keyword=regenerative therapy kn-keyword=regenerative therapy END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=13 article-no= start-page=7238 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250627 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Protective Effects of the Ethyl Acetate Fraction of Distylium racemosum Against Metabolic Dysfunction-Associated Steatohepatitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metabolic dysfunction-associated steatohepatitis (MASH), previously referred to as non-alcoholic steatohepatitis (NASH), which is a progressive non-alcoholic fatty liver disease, is accompanied by hepatic steatosis, inflammation, and fibrosis. Despite its increasing prevalence, available treatment options for MASH are limited. Here, we investigated the protective effects of the Distylium racemosum ethyl acetate fraction (DRE) using MASH models and explored its key physiologically active components. Palmitic acid (PA)-induced AML12 hepatocytes and high-fat methionine- and choline-deficient-fed C57BL/6 mice were used as MASH models. Lipid accumulation was evaluated via triglyceride measurement, oil red O staining, and histological analysis. Lipid accumulation, inflammation, and fibrosis-associated gene expression were evaluated via real-time polymerase chain reaction. The physiologically active components of DRE were identified via high-performance liquid chromatography. Lipid accumulation and triglyceride levels were significantly reduced in PA-treated AML12 cells following DRE treatment. Additionally, DRE inhibited the expression of genes involved in lipogenesis (FAS and SREBP1c), inflammation (CD68, IL-6, and MCP-1), and fibrosis (COL1A1, COL1A2, and TIMP1). DRE reduced the liver weight, liver-to-body weight ratio, and hepatic steatosis in MASH model mice. It increased carnitine palmitoyltransferase-1 levels and decreased CD36 and transforming growth factor-β levels in the MASH mouse liver. High-performance liquid chromatography revealed that the extract contained rutin flavonoid family members. Overall, DRE was involved in lipid metabolism, inflammation, and fibrosis regulation, exerting potent hepatoprotective effects partly attributed to rutin and serving as a potential preventive candidate for MASH. en-copyright= kn-copyright= en-aut-name=LeeYoung-Hyeon en-aut-sei=Lee en-aut-mei=Young-Hyeon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YeoMin-Ho en-aut-sei=Yeo en-aut-mei=Min-Ho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChangKyung-Soo en-aut-sei=Chang en-aut-mei=Kyung-Soo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoonWeon-Jong en-aut-sei=Yoon en-aut-mei=Weon-Jong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimHye-Sook en-aut-sei=Kim en-aut-mei=Hye-Sook kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KimJongwan en-aut-sei=Kim en-aut-mei=Jongwan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimHye-Ran en-aut-sei=Kim en-aut-mei=Hye-Ran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=2 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=3 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=4 en-affil=Clean Bio Business Division, Biodiversity Research Institute (JBRI), Jeju Technopark (JTP) kn-affil= affil-num=5 en-affil=Department of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Anatomy, College of Medicine, Dongguk University kn-affil= affil-num=7 en-affil=Department of Biomedical Laboratory Science, Dong-Eui Institute of Technology kn-affil= en-keyword=metabolic dysfunction-associated steatohepatitis kn-keyword=metabolic dysfunction-associated steatohepatitis en-keyword=Distylium racemosum kn-keyword=Distylium racemosum en-keyword=ethyl acetate fraction kn-keyword=ethyl acetate fraction en-keyword=extract kn-keyword=extract END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=8 article-no= start-page=1621 end-page=1630 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Percutaneous cryoablation versus robot-assisted partial nephrectomy for small renal cell carcinoma: a retrospective cost analysis at Japanese single-institution en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: No direct cost comparison has been conducted between percutaneous cryoablation (PCA) and robot-assisted partial nephrectomy (RAPN) for clinical T1a renal cell carcinoma (RCC) in Japan. This study aimed to compare their costs.
Methods: We retrospectively analyzed data from 212 PCAs (including 155 with transcatheter arterial embolization) and 119 RAPN cases performed between December 2017 and May 2022.
Results: PCA patients were older with higher American Society of Anesthesiologists scores, Charlson Comorbidity Index, and history of previous RCC treatment, cardiovascular disease, and antithrombotic drug use than RAPN patients. PCA was associated with a significantly shorter procedure time and hospitalization duration with fewer major complications than those associated with RAPN. While PCA incurred a slightly lower total cost (1,123,000 vs. 1,155,000 yen), it had a significantly higher procedural cost (739,000 vs. 693,000 yen) and markedly worse total (? 93,000 vs. 249,000 yen) and procedural income-expenditure balance (? 189,000 vs. 231,000 yen) than those of RAPN. After statistical adjustment, PCA demonstrated significantly higher total (difference: 114,000 yen) and procedural costs (difference: 72,000 yen), alongside significantly worse total (difference: ? 358,000 yen) and procedural income-expenditure balances (difference: ? 439,000 yen). The incremental cost-effectiveness ratio was more favorable for PCA than for RAPN.
Conclusion: For high- risk patients, PCA demonstrated a safer option with shorter hospitalization duration than those of RAPN. Although PCA was more cost-effective, its higher procedural cost and unfavorable income-expenditure balance require careful evaluation, especially for large tumors that require three or more needles. en-copyright= kn-copyright= en-aut-name=UkaMayu en-aut-sei=Uka en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 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=5 ORCID= en-aut-name=GobaraHideo en-aut-sei=Gobara en-aut-mei=Hideo 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=KawabataTakahiro en-aut-sei=Kawabata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=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=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo 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 Radiology, Okayama University Hospital 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=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Medical Informatics, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Radiology, 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 Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Renal cancer kn-keyword=Renal cancer en-keyword=Cryoablation kn-keyword=Cryoablation en-keyword=Robot-assisted partial nephrectomy kn-keyword=Robot-assisted partial nephrectomy en-keyword=Cost kn-keyword=Cost en-keyword=Cost effectiveness kn-keyword=Cost effectiveness END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=27163 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Eosinophils as a predictive marker of treatment-related adverse events in mRCC patients treated with first-line immune-checkpoint inhibitor combination therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immune checkpoint inhibitors (ICIs) are a key component of first-line treatment for metastatic renal cell carcinoma (mRCC). However, predicting treatment-related adverse events (TRAEs) remains challenging. This study investigated the utility of eosinophil-related biomarkers as predictors of Common Terminology Criteria for Adverse Events grade???3 TRAEs in mRCC patients undergoing ICI combination therapy. In this retrospective analysis across 21 hospitals in Japan, we examined 180 patients treated with ICI/ICI therapy and 216 patients treated with ICI/tyrosine kinase inhibitor (TKI) therapy. Grade???3 TRAEs occurred in 39.4% and 31.9% of patients in the ICI/ICI and ICI/TKI groups, respectively. An elevated eosinophil proportion of???2.0% (odds ratio [OR]: 2.36; 95% CI [confidence interval] 1.23?4.54, p?=?0.01) and a low neutrophil/eosinophil ratio (NER) of???40.0 (OR: 2.78, 95% CI 1.39?5.53, p?=?0.004) were significant predictors of severe TRAEs in the ICI/ICI group. However, no significant associations were found in the ICI/TKI group. These findings may help identify patients who suffer from grade???3 TRAEs and help determine individualized treatment strategies in patients with mRCC. en-copyright= kn-copyright= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukuokayaWataru en-aut-sei=Fukuokaya en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=TsujinoTakuya en-aut-sei=Tsujino en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaenosonoRyoichi en-aut-sei=Maenosono en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakaharaKiyoshi en-aut-sei=Takahara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=InokiLan en-aut-sei=Inoki en-aut-mei=Lan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=HashimotoTakeshi en-aut-sei=Hashimoto en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HirasawaYosuke en-aut-sei=Hirasawa en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 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=20 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=21 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=22 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=23 ORCID= en-aut-name=TsuboiKazuma en-aut-sei=Tsuboi en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=TakamotoAtsushi en-aut-sei=Takamoto en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KuroseKyohei en-aut-sei=Kurose en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 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=28 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=29 ORCID= en-aut-name=ShirokiRyoichi en-aut-sei=Shiroki en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 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=31 ORCID= en-aut-name=OhnoYoshio en-aut-sei=Ohno en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 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=33 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, The Jikei University School of Medicine kn-affil= affil-num=4 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=6 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=7 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=8 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=9 en-affil=Department of Urology, Fujita Health University School of Medicine kn-affil= affil-num=10 en-affil=Department of Urology, Fujita Health University School of Medicine kn-affil= affil-num=11 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=13 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=14 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=22 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=24 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=25 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=26 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=27 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=28 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=29 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=30 en-affil=Department of Urology, Fujita Health University School of Medicine kn-affil= affil-num=31 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=32 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=33 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Renal cell carcinoma kn-keyword=Renal cell carcinoma en-keyword=Immune checkpoint inhibitor kn-keyword=Immune checkpoint inhibitor en-keyword=ICI kn-keyword=ICI en-keyword=Eosinophil kn-keyword=Eosinophil en-keyword=Immune-related adverse event kn-keyword=Immune-related adverse event en-keyword=Treatment-related adverse event kn-keyword=Treatment-related adverse event END start-ver=1.4 cd-journal=joma no-vol=135 cd-vols= no-issue=13 article-no= start-page=e172988 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250513 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=LAG3 regulates antibody responses in a murine model of kidney transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Lymphocyte activation gene 3 (LAG3) is a coinhibitory receptor expressed by various immune cells. Although the immunomodulatory potential of LAG3 is being explored in cancer and autoimmunity, there is no information on its role after organ transplantation. Our study investigated the functions of LAG3 in a mouse model of renal allograft rejection. LAG3?/? recipients rapidly rejected MHC-mismatched renal allografts that were spontaneously accepted by WT recipients, with graft histology characteristic of antibody-mediated rejection. Depletion of recipient B cells but not CD8+ T cells significantly extended kidney allograft survival in LAG3?/? recipients. Treatment of WT recipients with an antagonistic LAG3 antibody enhanced anti-donor immune responses and induced kidney damage associated with chronic rejection. The studies of conditional LAG3?/? recipients and mixed bone marrow chimeras demonstrated that LAG3 expression on either T or B cells is sufficient to regulate anti-donor humoral immunity but not to induce acute allograft rejection. The numbers and proinflammatory functions of graft-infiltrating NK cells were markedly increased in LAG3?/? recipients, suggesting that LAG3 also regulates the effector stage of antibody-mediated rejection. These findings identified LAG3 as a regulator of immune responses to kidney allografts and a potential therapeutic target for antibody-mediated rejection prevention and treatment. en-copyright= kn-copyright= en-aut-name=NicosiaMichael en-aut-sei=Nicosia en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FanRan en-aut-sei=Fan en-aut-mei=Ran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LeeJuyeun en-aut-sei=Lee en-aut-mei=Juyeun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AllGabriella en-aut-sei=All en-aut-mei=Gabriella kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GorbachevaVictoria en-aut-sei=Gorbacheva en-aut-mei=Victoria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ValenzuelaJos? I. en-aut-sei=Valenzuela en-aut-mei=Jos? I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoYosuke en-aut-sei=Yamamoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BeaversAshley en-aut-sei=Beavers en-aut-mei=Ashley kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DvorinaNina en-aut-sei=Dvorina en-aut-mei=Nina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=BaldwinWilliam M. en-aut-sei=Baldwin en-aut-mei=William M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ChuluyanEduardo en-aut-sei=Chuluyan en-aut-mei=Eduardo 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=GaudetteBrian T. en-aut-sei=Gaudette en-aut-mei=Brian T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FairchildRobert L. en-aut-sei=Fairchild en-aut-mei=Robert L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MinBooki en-aut-sei=Min en-aut-mei=Booki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ValujskikhAnna en-aut-sei=Valujskikh en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=2 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=3 en-affil=Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=4 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=5 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=6 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=7 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=8 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=9 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=10 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=11 en-affil=Universidad de Buenos Aires, Consejo Nacional de Investigaciones Cient?ficas y T?cnicas, Centro de Estudios Farmacol?gicos y Bot?nicos (CEFYBO), Facultad de Medicina 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 Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=14 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=15 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=16 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=5 article-no= start-page=468 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Distribution of Fimbrial Genes and Their Association with Virulence and Levofloxacin Resistance/Extended-Spectrum Beta-Lactamase Production in Uropathogenic Escherichia coli en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Urinary tract infection (UTI) is predominantly caused by uropathogenic Escherichia coli (UPEC). Previous studies have reported that the fimbriae of UPEC are involved in virulence and antimicrobial resistance. We aimed to analyze the fimbrial gene profiles of UPEC and investigate the specificity of these expressions in symptomatic UTI, urinary device use, and levofloxacin (LVFX) resistance/extended-spectrum beta-lactamase (ESBL) production. Methods: A total of 120 UPEC strains were isolated by urine culture between 2019 and 2023 at our institution. They were subjected to an antimicrobial susceptibility test and polymerase chain reaction (PCR) to identify 14 fimbrial genes and their association with clinical outcomes or antimicrobial resistance. Results: The prevalence of the papG2 gene was significantly higher in the symptomatic UTI group by multivariate analyses (OR 5.850, 95% CI 1.390?24.70, p = 0.016). The prevalence of the c2395 gene tended to be lower in the symptomatic UTI group with urinary devices (all p < 0.05). In LVFX-resistant UPEC strains from both the asymptomatic bacteriuria (ABU) and the symptomatic UTI group, the expression of the papEF, papG3, c2395, and yadN genes tended to be lower (all p < 0.05). Conclusion: The fimbrial genes of UPEC are associated with virulence and LVFX resistance, suggesting that even UPEC with fewer motility factors may be more likely to ascend the urinary tract in the presence of the urinary devices. These findings may enhance not only the understanding of the virulence of UPEC but also the management of UTI. en-copyright= kn-copyright= en-aut-name=MitsuiMasao en-aut-sei=Mitsui en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SekitoTakanori en-aut-sei=Sekito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaruhashiMai en-aut-sei=Maruhashi en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaruyamaYuki en-aut-sei=Maruyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=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=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HirakawaHidetada en-aut-sei=Hirakawa en-aut-mei=Hidetada kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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 Bacteriology, Graduate School of Medicine, Gunma University 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= affil-num=11 en-affil=Department of Bacteriology, Graduate School of Medicine, Gunma University kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=fimbriae kn-keyword=fimbriae en-keyword=urinary tract infection kn-keyword=urinary tract infection en-keyword=drug resistance kn-keyword=drug resistance en-keyword=virulence kn-keyword=virulence en-keyword=uropathogenic Escherichia coli kn-keyword=uropathogenic Escherichia coli END start-ver=1.4 cd-journal=joma no-vol=144-145 cd-vols= no-issue= article-no= start-page=109001 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Investigating the fate of Zirconium-89 labelled antibody in cynomolgus macaques en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Preclinical pharmacokinetic studies of therapeutic antibodies in non-human primates are desired because of the difficulty in extrapolating ADME data from animal models to humans. We evaluated the pharmacokinetics of 89Zr (Zirconium-89) -labelled anti-KLH human IgG and its metabolites to confirm their non-specific/physiological accumulation in healthy cynomolgus macaques. The anti-KLH antibody was used as a negative control, ensuring that the observed distribution reflected general IgG behavior rather than antigen-specific accumulation. This provides a valuable reference for comparing the biodistribution of targeted antibodies.
Methods: Selected IgG was conjugated to desferrioxamine (DFO), labelled with 89Zr, and injected into healthy cynomolgus macaques. PET/CT images at the whole-body level were acquired at different time points, and standard uptake values (SUV) in regions of interest, such as the heart, liver, spleen, kidneys, bone, and muscles, were calculated. The distribution of a shortened antibody variant, 89Zr-labelled Fab, as well as that of [89Zr]Zr-DFO and [89Zr]Zr-oxalate, the expected metabolites of 89Zr- labelled IgG, was also assessed.
Results: After 89Zr-labelled IgG injection, the SUV in the heart, vertebral body, and muscle decreased, in line with the 89Zr concentration decrease in the circulation, whereas radioactivity increased over time in the kidneys and liver. Autoradiography of the renal sections indicated that most of the 89Zr- labelled IgG radioactivity accumulated in the renal cortex. Relatively high accumulation in the kidneys was also observed in 89Zr- labelled Fab-injected macaques, and renal autoradiographs of these animals showed that the renal cortex was the preferred accumulation site. However, [89Zr]Zr-DFO was rapidly excreted into the urine, whereas [89Zr]Zr-oxalate was highly accumulated in the epiphysis of the long bones and vertebral body.
Conclusion: In the non-human primate cynomolgus macaque, 89Zr- labelled IgG accumulated in the kidneys and the liver. However, [89Zr]Zr-DFO and 89Zr did not accumulate in these organs. This preclinical pharmacokinetic study performed with human IgG in a non-human primate model using PET is of great significance as it sheds light on the basic fate and distribution of 89Zr- labelled IgG. en-copyright= kn-copyright= en-aut-name=SasakiTakanori en-aut-sei=Sasaki en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraSadaaki en-aut-sei=Kimura en-aut-mei=Sadaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NodaAkihiro en-aut-sei=Noda en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MurakamiYoshihiro en-aut-sei=Murakami en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyoshiSosuke en-aut-sei=Miyoshi en-aut-mei=Sosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkehiMasaru en-aut-sei=Akehi en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OchiaiKazuhiko en-aut-sei=Ochiai en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=HiguchiTakahiro en-aut-sei=Higuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Astellas Pharma Inc. kn-affil= affil-num=3 en-affil=Astellas Pharma Inc. kn-affil= affil-num=4 en-affil=Astellas Pharma Inc. kn-affil= affil-num=5 en-affil=Astellas Pharma Inc. kn-affil= affil-num=6 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=School of Veterinary Nursing and Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=8 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=PET imaging kn-keyword=PET imaging en-keyword=Zirconium-89 kn-keyword=Zirconium-89 en-keyword=Therapeutic antibodies kn-keyword=Therapeutic antibodies en-keyword=Non-human primates kn-keyword=Non-human primates END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=3 article-no= start-page=e70085 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Acute effect of multipoint pacing and fused AV delay in patients receiving cardiac resynchronization therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure with dyssynchrony. However, one-third of patients do not respond positively to it. Recently, multipoint pacing (MPP), which involves pacing from two sites on the left ventricle, has been found to improve symptoms and hemodynamics compared to conventional CRT. An automatic fused atrioventricular (AV) delay that performs fused pacing for intrinsic conduction has also been introduced. However, the combined effect of MPP and fused AV delay on acute hemodynamics is unknown.
Objective: To evaluate the acute hemodynamic effects of MPP and fused AV delay in patients undergoing CRT.
Methods: A pressure wire was delivered to the left ventricle, and dp/dt was compared with single atrial stimulation pacing in 52 patients with various pacing configurations.
Results: Delta dp/dt was greater in MPP than in conventional CRT (10.5?±?1.0% vs. 8.2?±?1.0%, p? Conclusion: Combining MPP and fused AV delay has an additional effect. Shortening the QRS duration can increase the dp/dt, but the estimated line differs between LV and BiV pacing. en-copyright= kn-copyright= en-aut-name=MiyamotoMasakazu en-aut-sei=Miyamoto en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiiNobuhiro en-aut-sei=Nishii en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MizunoTomofumi en-aut-sei=Mizuno en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UeokaAkira en-aut-sei=Ueoka en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasudaTakuro en-aut-sei=Masuda en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsadaSaori en-aut-sei=Asada en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=KawadaSatoshi en-aut-sei=Kawada en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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 Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=cardiac resynchronization therapy kn-keyword=cardiac resynchronization therapy en-keyword=dp/dt kn-keyword=dp/dt en-keyword=fused AV delay kn-keyword=fused AV delay en-keyword=LV pacing kn-keyword=LV pacing en-keyword=multipoint pacing kn-keyword=multipoint pacing END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=3 article-no= start-page=444 end-page=451 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=More postoperative complications and revision surgery after occipitocervical fusion than after atlantoaxial fusion: a retrospective multicenter cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Study Design: A retrospective multicenter cohort study.
Purpose: We sought to determine whether occipitocervical (OC) fusion is followed by more postoperative complications and revision surgery than is atlantoaxial (AA) fusion. We aim to compare postoperative complications and revision surgery associated with OC fusion and AA fusion.
Overview of Literature: OC and AA fusion are established techniques for restoring upper cervical stability. However, the outcomes of the two methods have not been compared.
Methods: This study included 90 patients who underwent upper spinal fusion surgery for mechanical instability, performed by three surgeons in two hospitals from 2011 to 2023; OC fusion was indicated for irreducible AA subluxation, os odontoideum, and severe upper C1 fracture. Of the patients, 38 (mean age, 58.7 years) underwent OC fusion, and 52 (mean age, 62.8 years) underwent AA fusion. To evaluate surgical outcomes, we documented surgical time, intraoperative blood loss, postoperative complications, and the rate of revision surgery. Radiographs were obtained to identify screw malposition, rod breakage, and nonunion. To compare the outcomes of the two techniques, we used the Mann-Whitney U test for continuous variables and the chi-square or Fisher’s exact test for dichotomous variables.
Results: OC fusion took significantly longer (175.4 minutes) than AA fusion (150.7 minutes, p=0.020) and had a higher complication rate (39.5% vs. 11.5%, p<0.0001). The reoperation rate was 23.7% (9/38) after OC fusion and 3.8% (2/52) after AA fusion; the difference was statistically significant (p=0.0073). Average amounts of blood loss were 224 mL during OC fusion and 224 mL during AA fusion; the difference was not significant (p=0.947).
Conclusions: Although OC fusion is indispensable for certain conditions, particularly basilar invagination, it entails more risk than dose AA fusion; the choice of technique thus warrants careful consideration. 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=FloresAngel Oscar Paz en-aut-sei=Flores en-aut-mei=Angel Oscar Paz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=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=AratakiShinya en-aut-sei=Arataki en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital 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=Department of Orthopaedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= en-keyword=Occipitocervical fusion kn-keyword=Occipitocervical fusion en-keyword=Atlantoaxial fusion kn-keyword=Atlantoaxial fusion en-keyword=Upper cervical instability kn-keyword=Upper cervical instability en-keyword=Surgical complication kn-keyword=Surgical complication en-keyword=Reoperation kn-keyword=Reoperation END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=15 article-no= start-page=7275 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Acquired Radioresistance Through Adaptive Evolution with Gamma Radiation as Selection Pressure: Increased Expression and Induction of Anti-Stress Genes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Elucidating the mechanisms of radioresistance in highly radiotolerant organisms can provide valuable insights into the adaptation and evolution of organisms. However, research has been limited on many naturally occurring radioresistant organisms due to a lack of information regarding their genetic and biochemical characteristics and the difficulty of handling them experimentally. To address this, we conducted an experiment on adaptive evolution using gamma radiation as the selection pressure to generate evolved Escherichia coli with gamma radiation resistance approximately one order of magnitude greater than that of wild-type E. coli. Gene expressions in all wild-type and evolved radioresistant E. coli in the presence or absence of gamma irradiation were analyzed and compared using RNA sequencing. Under steady-state conditions, the genes involved in survival, cell recovery, DNA repair, and response following stress exposure were upregulated in evolved E. coli compared with those in wild-type E. coli. Furthermore, the evolved E. coli induced these genes more efficiently following gamma irradiation and greater DNA repair activity than that in the wild-type E. coli. Our results indicate that an increased steady-state expression of various anti-stress genes, including DNA repair-related genes, and their highly efficient induction under irradiation are responsible for the remarkable radioresistance of evolved E. coli. en-copyright= kn-copyright= en-aut-name=SaitoTakeshi en-aut-sei=Saito en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeratoHiroaki en-aut-sei=Terato en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Division of Radiation Life Science, Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=2 en-affil=Department of Radiation Research, Advanced Science Research Center, Okayama University kn-affil= en-keyword=radioresistant bacteria kn-keyword=radioresistant bacteria en-keyword=Escherichia coli kn-keyword=Escherichia coli en-keyword=adaptive evolution kn-keyword=adaptive evolution en-keyword=gene expression changes kn-keyword=gene expression changes en-keyword=anti-stress genes kn-keyword=anti-stress genes en-keyword=DNA repair kn-keyword=DNA repair en-keyword=cell recovery kn-keyword=cell recovery END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=7 article-no= start-page=koaf142 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pancentromere analysis of Allium species reveals diverse centromere positions in onion and gigantic centromeres in garlic en-subtitle= kn-subtitle= en-abstract= kn-abstract=In eukaryotes, centromeres interact with the kinetochore for distribution of genetic information in cell division, yet their sequence and size are diverse among species. However, their position on chromosomes is considered to be conserved within a species. In this study, we analyzed the centromeres of 3 Allium species, namely, Welsh onion (Allium fistulosum), onion (Allium cepa), and garlic (Allium sativum) via pancentromere analysis and repetitive sequence analysis of centromeres and their neighborhoods and revealed their mobility, sequence organization, and size. Among the 3 species, Welsh onion and garlic had stable centromeres, but the onion centromere appeared to be polymorphic and frequently differed in position by up to 28.0?Mb among cultivars and between multiple individuals of the same cultivar. This mobility was stabilized by hybridization with Welsh onions. Furthermore, these 3 species have very different centromere sequence organization, including differences in the existence and maturity of centromeric satellites, and differences in centromere size, with Welsh onion having a centromere of 1.9?Mb, and garlic having a centromere of ?10.6?Mb, the largest of any organism with monocentric chromosomes analyzed to date. Our pancentromere analysis of these Allium species reveals the variation in sequence organization, size, and position of this important chromosomal region. en-copyright= kn-copyright= en-aut-name=NagakiKiyotaka en-aut-sei=Nagaki en-aut-mei=Kiyotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UshijimaKoichiro en-aut-sei=Ushijima en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AkagiTakashi en-aut-sei=Akagi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaKeisuke en-aut-sei=Tanaka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiHisato en-aut-sei=Kobayashi en-aut-mei=Hisato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=NODAI Genome Research Center, Tokyo University of Agriculture kn-affil= affil-num=5 en-affil=NODAI Genome Research Center, Tokyo University of Agriculture kn-affil= END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=1041 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250318 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Longitudinal changes and tracking of in-school physical activity in primary school children: four-year longitudinal study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background There is little evidence on the tracking of physical activity during school hours. In addition, tracking physical activity in schools provides important evidence for understanding children’s physical activity and conducting intervention studies. Therefore, this study examined longitudinal changes and tracking of in-school physical activity in primary school children.
Methods In this study, physical activity was investigated longitudinally in primary school children for 4 years. The baseline participants consisted of 103 second-grade students (7?8 years old) who participated. Step counts and moderate-to-vigorous physical activity (MVPA) in school and during first recess and lunch/second recess were examined using an accelerometer (Kenz Lifecorder GS 4-second version; Suzuken Co. Ltd, Nagoya, Japan).
Results After excluding missing data (moving school; n?=?8, physical activity; n?=?8), 87 (43 boys and 44 girls) of whom were included in the final analysis. Step counts and MVPA during school and physical education in boys did not decrease across the school years. By contrast, in girls, step counts during school did not decrease across the school years, however MVPA did decrease. In addition, for both sexes, step counts and MVPA during first recess decrease across the school years. During lunch/second recess, only step counts decrease across the school years in both sexes. In addition, the tracking coefficients for step counts and MVPA for boys in school and during first recess and lunch/second recess were found across many school years. Contrarily, girls had fewer significant tracking coefficients between school years than boys. There were also few significant tracking coefficients between grades for physical education step counts and MVPA for both boys and girls.
Conclusions Our results suggested that in-school step counts for both boys and girls does not decrease across the school years. However, given that girls demonstrated reduced levels of in-school MVPA across the school years, it is important to promote strategies to increase MVPA in this group. en-copyright= kn-copyright= en-aut-name=SasayamaKensaku en-aut-sei=Sasayama en-aut-mei=Kensaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YasunebeJin en-aut-sei=Yasunebe en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AdachiMinoru en-aut-sei=Adachi en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Faculty of Education, Mie University kn-affil= affil-num=2 en-affil=Faculty of Education, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Education, Okayama University kn-affil= en-keyword=Physical activity kn-keyword=Physical activity en-keyword=Step counts kn-keyword=Step counts en-keyword=Moderate-to-vigorous physical activity kn-keyword=Moderate-to-vigorous physical activity en-keyword=Youth kn-keyword=Youth en-keyword=Recess kn-keyword=Recess en-keyword=Physical education kn-keyword=Physical education en-keyword=Longitudinal study kn-keyword=Longitudinal study en-keyword=Tracking kn-keyword=Tracking END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=10 article-no= start-page=2401783 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biocompatibility of Water-Dispersible Pristine Graphene and Graphene Oxide Using a Close-to-Human Animal Model: A Pilot Study on Swine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Graphene-based materials (GBMs) are of considerable interest for biomedical applications, and the pilot study on the toxicological and immunological impact of pristine graphene (GR) and graphene oxide (GO) using swine as a close-to-human provides valuable insights. First, ex vivo experiments are conducted on swine blood cells, then GBMs are injected intraperitoneally (i.p.) into swine. Hematological and biochemical analyses at various intervals indicate that neither GO nor GR cause systemic inflammation, pro-coagulant responses, or renal or hepatic dysfunction. Importantly, no systemic toxicity is observed. Analysis of a panel of 84 immune-related genes shows minimal impact of GO and GR. The animals are sacrificed 21 days post-injection, and transient absorption imaging and Raman mapping show the presence of GO and GR in the mesentery only. Histological evaluation reveals no signs of alterations in other organs. Thus, clusters of both materials are detected in the mesentery, and GO aggregates are surrounded only by macrophages with the formation of granulomas. In contrast, modest local reactions are observed around the GR clusters. Overall, these results reveal that i.p. injection of GBMs resulted in a modest local tissue reaction without systemic toxicity. This study, performed in swine, provides essential guidance for future biomedical applications of graphene. en-copyright= kn-copyright= en-aut-name=NicolussiPaola en-aut-sei=Nicolussi en-aut-mei=Paola kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PiloGiovannantonio en-aut-sei=Pilo en-aut-mei=Giovannantonio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=CanceddaMaria Giovanna en-aut-sei=Cancedda en-aut-mei=Maria Giovanna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PengGuotao en-aut-sei=Peng en-aut-mei=Guotao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChauNgoc Do Quyen en-aut-sei=Chau en-aut-mei=Ngoc Do Quyen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=De la CadenaAlejandro en-aut-sei=De la Cadena en-aut-mei=Alejandro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=VannaRenzo en-aut-sei=Vanna en-aut-mei=Renzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SamadYarjan Abdul en-aut-sei=Samad en-aut-mei=Yarjan Abdul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AhmedTanweer en-aut-sei=Ahmed en-aut-mei=Tanweer kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MarcellinoJeremia en-aut-sei=Marcellino en-aut-mei=Jeremia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TeddeGiuseppe en-aut-sei=Tedde en-aut-mei=Giuseppe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GiroLinda en-aut-sei=Giro en-aut-mei=Linda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YlmazerAcelya en-aut-sei=Ylmazer en-aut-mei=Acelya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=LoiFederica en-aut-sei=Loi en-aut-mei=Federica kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=CartaGavina en-aut-sei=Carta en-aut-mei=Gavina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SecchiLoredana en-aut-sei=Secchi en-aut-mei=Loredana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Dei GiudiciSilvia en-aut-sei=Dei Giudici en-aut-mei=Silvia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MacciocuSimona en-aut-sei=Macciocu en-aut-mei=Simona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=PolliDario en-aut-sei=Polli en-aut-mei=Dario kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=LigiosCiriaco en-aut-sei=Ligios en-aut-mei=Ciriaco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=CerulloGiulio en-aut-sei=Cerullo en-aut-mei=Giulio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FerrariAndrea en-aut-sei=Ferrari en-aut-mei=Andrea kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=BiancoAlberto en-aut-sei=Bianco en-aut-mei=Alberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=FadeelBengt en-aut-sei=Fadeel en-aut-mei=Bengt kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=FranzoniGiulia en-aut-sei=Franzoni en-aut-mei=Giulia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=DeloguLucia Gemma en-aut-sei=Delogu en-aut-mei=Lucia Gemma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= affil-num=1 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=2 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=3 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=4 en-affil=Institute of Environmental Medicine, Karolinska Institutet kn-affil= affil-num=5 en-affil=CNRS, Immunology, Immunopathology and Therapeutic Chemistry kn-affil= affil-num=6 en-affil=Dipartimento di Fisica, Politecnico di Milano kn-affil= affil-num=7 en-affil=Istituto di Fotonica e Nanotecnologie ? CNR kn-affil= affil-num=8 en-affil=Cambridge Graphene Centre, University of Cambridge kn-affil= affil-num=9 en-affil=Cambridge Graphene Centre, University of Cambridge kn-affil= affil-num=10 en-affil=Cambridge Graphene Centre, University of Cambridge kn-affil= affil-num=11 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=12 en-affil=ImmuneNano Laboratory, Department of Biomedical Sciences kn-affil= affil-num=13 en-affil=Department of Biomedical Engineering, Ankara University kn-affil= affil-num=14 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=15 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=16 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=17 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=18 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=19 en-affil=Dipartimento di Fisica, Politecnico di Milano kn-affil= affil-num=20 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=21 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=22 en-affil=Dipartimento di Fisica, Politecnico di Milano kn-affil= affil-num=23 en-affil=Cambridge Graphene Centre, University of Cambridge kn-affil= affil-num=24 en-affil=CNRS, Immunology, Immunopathology and Therapeutic Chemistry kn-affil= affil-num=25 en-affil=Institute of Environmental Medicine, Karolinska Institutet kn-affil= affil-num=26 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=27 en-affil=ImmuneNano Laboratory, Department of Biomedical Sciences kn-affil= en-keyword=2D materials kn-keyword=2D materials en-keyword=biocompatibility kn-keyword=biocompatibility en-keyword=immune system kn-keyword=immune system en-keyword=porcine model kn-keyword=porcine model en-keyword=toxicity kn-keyword=toxicity END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=4 article-no= start-page=263 end-page=272 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240607 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Light-Responsive and Antibacterial Graphenic Materials as a Holistic Approach to Tissue Engineering en-subtitle= kn-subtitle= en-abstract= kn-abstract=While the continuous development of advanced bioprinting technologies is under fervent study, enhancing the regenerative potential of hydrogel-based constructs using external stimuli for wound dressing has yet to be tackled. Fibroblasts play a significant role in wound healing and tissue implants at different stages, including extracellular matrix production, collagen synthesis, and wound and tissue remodeling. This study explores the synergistic interplay between photothermal activity and nanomaterial-mediated cell proliferation. The use of different graphene-based materials (GBM) in the development of photoactive bioinks is investigated. In particular, we report the creation of a skin-inspired dressing for wound healing and regenerative medicine. Three distinct GBM, namely, graphene oxide (GO), reduced graphene oxide (rGO), and graphene platelets (GP), were rigorously characterized, and their photothermal capabilities were elucidated. Our investigations revealed that rGO exhibited the highest photothermal efficiency and antibacterial properties when irradiated, even at a concentration as low as 0.05 mg/mL, without compromising human fibroblast viability. Alginate-based bioinks alongside human fibroblasts were employed for the bioprinting with rGO. The scaffold did not affect the survival of fibroblasts for 3 days after bioprinting, as cell viability was not affected. Remarkably, the inclusion of rGO did not compromise the printability of the hydrogel, ensuring the successful fabrication of complex constructs. Furthermore, the presence of rGO in the final scaffold continued to provide the benefits of photothermal antimicrobial therapy without detrimentally affecting fibroblast growth. This outcome underscores the potential of rGO-enhanced hydrogels in tissue engineering and regenerative medicine applications. Our findings hold promise for developing game-changer strategies in 4D bioprinting to create smart and functional tissue constructs with high fibroblast proliferation and promising therapeutic capabilities in drug delivery and bactericidal skin-inspired dressings. en-copyright= kn-copyright= en-aut-name=FerrerasAndrea en-aut-sei=Ferreras en-aut-mei=Andrea kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatesanzAna en-aut-sei=Matesanz en-aut-mei=Ana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MendizabalJabier en-aut-sei=Mendizabal en-aut-mei=Jabier kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArtolaKoldo en-aut-sei=Artola en-aut-mei=Koldo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AcedoPablo en-aut-sei=Acedo en-aut-mei=Pablo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=JorcanoJos? L. en-aut-sei=Jorcano en-aut-mei=Jos? L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=RuizAmalia en-aut-sei=Ruiz en-aut-mei=Amalia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ReinaGiacomo en-aut-sei=Reina en-aut-mei=Giacomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Mart?nCristina en-aut-sei=Mart?n en-aut-mei=Cristina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Bioengineering, Universidad Carlos III de Madrid kn-affil= affil-num=2 en-affil=Department of Electronic Technology, Universidad Carlos III de Madrid kn-affil= affil-num=3 en-affil=Domotek ingenier?a prototipado y formaci?n S.L. kn-affil= affil-num=4 en-affil=Domotek ingenier?a prototipado y formaci?n S.L. 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 Electronic Technology, Universidad Carlos III de Madrid kn-affil= affil-num=7 en-affil=Department of Bioengineering, Universidad Carlos III de Madrid kn-affil= affil-num=8 en-affil=Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford kn-affil= affil-num=9 en-affil=Empa Swiss Federal Laboratories for Materials Science and Technology kn-affil= affil-num=10 en-affil=Department of Bioengineering, Universidad Carlos III de Madrid kn-affil= en-keyword=photothermal therapy kn-keyword=photothermal therapy en-keyword=graphene derivatives kn-keyword=graphene derivatives en-keyword=4D bioprinting kn-keyword=4D bioprinting en-keyword=alginate kn-keyword=alginate en-keyword=tissue engineering kn-keyword=tissue engineering END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue=12 article-no= start-page=4932 end-page=4951 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The leucine-rich repeat receptor kinase QSK1 regulates PRR-RBOHD complexes targeted by the bacterial effector HopF2Pto en-subtitle= kn-subtitle= en-abstract= kn-abstract=Plants detect pathogens using cell-surface pattern recognition receptors (PRRs) such as ELONGATION Factor-TU (EF-TU) RECEPTOR (EFR) and FLAGELLIN SENSING 2 (FLS2), which recognize bacterial EF-Tu and flagellin, respectively. These PRRs belong to the leucine-rich repeat receptor kinase (LRR-RK) family and activate the production of reactive oxygen species via the NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD). The PRR-RBOHD complex is tightly regulated to prevent unwarranted or exaggerated immune responses. However, certain pathogen effectors can subvert these regulatory mechanisms, thereby suppressing plant immunity. To elucidate the intricate dynamics of the PRR-RBOHD complex, we conducted a comparative coimmunoprecipitation analysis using EFR, FLS2, and RBOHD in Arabidopsis thaliana. We identified QIAN SHOU KINASE 1 (QSK1), an LRR-RK, as a PRR-RBOHD complex-associated protein. QSK1 downregulated FLS2 and EFR abundance, functioning as a negative regulator of PRR-triggered immunity (PTI). QSK1 was targeted by the bacterial effector HopF2Pto, a mono-ADP ribosyltransferase, reducing FLS2 and EFR levels through both transcriptional and transcription-independent pathways, thereby inhibiting PTI. Furthermore, HopF2Pto transcriptionally downregulated PROSCOOP genes encoding important stress-regulated phytocytokines and their receptor MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2. Importantly, HopF2Pto requires QSK1 for its accumulation and virulence functions within plants. In summary, our results provide insights into the mechanism by which HopF2Pto employs QSK1 to desensitize plants to pathogen attack. en-copyright= kn-copyright= en-aut-name=GotoYukihisa en-aut-sei=Goto en-aut-mei=Yukihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KadotaYasuhiro en-aut-sei=Kadota en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MbengueMalick en-aut-sei=Mbengue en-aut-mei=Malick kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LewisJennifer D en-aut-sei=Lewis en-aut-mei=Jennifer D 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=MakiNoriko en-aut-sei=Maki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NgouBruno Pok Man en-aut-sei=Ngou en-aut-mei=Bruno Pok Man kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SklenarJan en-aut-sei=Sklenar en-aut-mei=Jan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DerbyshirePaul en-aut-sei=Derbyshire en-aut-mei=Paul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShibataArisa en-aut-sei=Shibata en-aut-mei=Arisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IchihashiYasunori en-aut-sei=Ichihashi en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GuttmanDavid S en-aut-sei=Guttman en-aut-mei=David S kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakagamiHirofumi en-aut-sei=Nakagami en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SuzukiTakamasa en-aut-sei=Suzuki en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MenkeFrank L H en-aut-sei=Menke en-aut-mei=Frank L H kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=RobatzekSilke en-aut-sei=Robatzek en-aut-mei=Silke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=DesveauxDarrell en-aut-sei=Desveaux en-aut-mei=Darrell kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ZipfelCyril en-aut-sei=Zipfel en-aut-mei=Cyril kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShirasuKen en-aut-sei=Shirasu en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=2 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=3 en-affil=The Sainsbury Laboratory, University of East Anglia kn-affil= affil-num=4 en-affil=Department of Cell and System Biology, Centre for the Analysis of Genome Function and Evolution, University of Toronto kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=7 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=8 en-affil=The Sainsbury Laboratory, University of East Anglia kn-affil= affil-num=9 en-affil=The Sainsbury Laboratory, University of East Anglia kn-affil= affil-num=10 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=11 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=12 en-affil=Department of Cell and System Biology, Centre for the Analysis of Genome Function and Evolution, University of Toronto kn-affil= affil-num=13 en-affil=Plant Proteomics Research Unit, RIKEN CSRS kn-affil= affil-num=14 en-affil=College of Bioscience and Biotechnology, Chubu University kn-affil= affil-num=15 en-affil=The Sainsbury Laboratory, University of East Anglia kn-affil= affil-num=16 en-affil=The Sainsbury Laboratory, University of East Anglia kn-affil= affil-num=17 en-affil=Department of Cell and System Biology, Centre for the Analysis of Genome Function and Evolution, University of Toronto kn-affil= affil-num=18 en-affil=Institute of Plant and Microbial Biology, Zurich-Basel Plant Science Center, University of Zurich kn-affil= affil-num=19 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) 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=2025 dt-pub=20250724 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Electrochemical Generation of Sulfonamidyl Radicals via Anodic Oxidation of Hydrogen Bonding Complexes: Applications to Electrosynthesis of Benzosultams en-subtitle= kn-subtitle= en-abstract= kn-abstract=Amidyl radicals and sulfonamidyl radicals are widely used in the field of organic synthesis. In particular, the electrochemical oxidation of amides in the presence of bases is one of the most practical methods for generating amidyl radicals. However, it is often difficult to observe the “true” radical precursor, such as an amide anion and/or a hydrogen bonding complex with an amide and a base. We found that a sulfonamide and Bu4NOAc form a 1:1 hydrogen bonding complex by spectroscopic experiments. Cyclic voltammetry suggested that 1:1 hydrogen bonding complexes should be oxidized predominantly under the optimized conditions to afford a sulfonamidyl radical via the proton-coupled electron transfer (PCET) process by the oxidation of the complex. Thus-generated sulfonamidyl radicals could be used in the electrochemical synthesis of a variety of benzosultams. en-copyright= kn-copyright= en-aut-name=OkumuraYasuyuki en-aut-sei=Okumura en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoEisuke en-aut-sei=Sato en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsudoKoichi en-aut-sei=Mitsudo en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SugaSeiji en-aut-sei=Suga en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=electrochemical generation kn-keyword=electrochemical generation en-keyword=sulfonamidyl radicals kn-keyword=sulfonamidyl radicals en-keyword=hydrogen bonding complexes kn-keyword=hydrogen bonding complexes en-keyword=anodic oxidation kn-keyword=anodic oxidation en-keyword=proton-coupled electron transfer kn-keyword=proton-coupled electron transfer en-keyword=electrosynthesis kn-keyword=electrosynthesis en-keyword=benzosultams kn-keyword=benzosultams en-keyword=cyclization kn-keyword=cyclization END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=7 article-no= start-page=e88945 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Six-Year Remission With No Relapse After Four-Time Weekly Rituximab Only for Bilateral Ocular Adnexal Follicular Lymphoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Follicular lymphoma mostly takes an indolent course, and thus, observation with watchful waiting is a main therapeutic strategy. Recent long-term studies suggest earlier treatment with rituximab monotherapy may benefit patients by delaying the need for treatment in the later phase of exacerbation. In this study, we reported a patient with bilateral orbital follicular lymphoma who received four-time weekly rituximab monotherapy as an induction therapy only and maintained the remission for 5 years with no treatment. The patient was a 51-year-old woman who developed a right upper orbital mass and was diagnosed with follicular lymphoma grade 1 by the excisional biopsy. Two years later, at the age of 53 years, she developed a left lacrimal gland mass and underwent excision. The pathological diagnosis was follicular lymphoma grade 1. She did not have any other systemic lesions by fluorodeoxyglucose positron emission tomography. At the age of 54 years, she developed a new mass on the nasal side of the right orbit and underwent weekly rituximab monotherapy (375 mg/m2) four times a month, leading to the reduction of the mass in 3 months. Two high uptake sites on the temporal and nasal side of the right superior orbit by fluorodeoxyglucose positron emission tomography disappeared one year later at the age of 55 years. She was followed with no treatment for 6 years until the age of 60 years at the latest visit. In case of a local orbital relapse, local radiotherapy would be the standard, but rituximab monotherapy as an induction therapy only was chosen in the present patient. Rituximab monotherapy in place of local radiotherapy would be a treatment option for orbital follicular lymphoma. 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=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=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, and Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Transfusion and Cell Therapy, Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=claustrophobia kn-keyword=claustrophobia en-keyword=extranodal marginal zone b-cell lymphoma mucosa-associated lymphoid tissue (malt) type kn-keyword=extranodal marginal zone b-cell lymphoma mucosa-associated lymphoid tissue (malt) type en-keyword=fluorodeoxyglucose positron emission tomography kn-keyword=fluorodeoxyglucose positron emission tomography en-keyword=follicular lymphoma kn-keyword=follicular lymphoma en-keyword=magnetic resonance imaging kn-keyword=magnetic resonance imaging en-keyword=mucosaassociated lymphoid tissue (malt) lymphoma kn-keyword=mucosaassociated lymphoid tissue (malt) lymphoma en-keyword=ocular adnexa kn-keyword=ocular adnexa en-keyword=orbital mass kn-keyword=orbital mass en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=rituximab kn-keyword=rituximab END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=6 article-no= start-page=271 end-page=285 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Sediment Microbial Fuel Cells on CH4 and CO2 Emissions from Straw Amended Paddy Soil en-subtitle= kn-subtitle= en-abstract= kn-abstract=Straw returning into paddy soil enhances soil organic matter which usually promotes the emission of greenhouse gases to the atmosphere. The application of sediment microbial fuel cells (SMFCs) to paddy soil activates power-generating microorganisms and enhances organic matter biodegradation. In the present study, rice straw addition in SMFCs was examined to determine its effect on CH4 and CO2 emissions. Columns (height, 25?cm; inner diameter, 9?cm) with four treatments: soil without and with rice straw under SMFC and without SMFC conditions were incubated at 25°C for 70 days. Anodic potential values at 7?cm depth sediment were kept higher by SMFCs than those without SMFCs. Cumulative CH4 emission was significantly reduced by SMFC with straw amendment (p < 0.05) with no significant effect on CO2 emission. 16S rRNA gene analysis results showed that Firmicutes at the phylum, Closteridiales and Acidobacteriales at order level were dominant on the anode of straw-added SMFC, whereas Methanomicrobiales were in the treatment without SMFC, indicating that a certain group of methanogens were suppressed by SMFC. Our results suggest that the anodic redox environment together with the enrichment of straw-degrading bacteria contributed to a competitive advantage of electrogenesis over methanogenesis in straw-added SMFC system. en-copyright= kn-copyright= en-aut-name=BekeleAdhena Tesfau en-aut-sei=Bekele en-aut-mei=Adhena Tesfau kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaedaMorihiro en-aut-sei=Maeda en-aut-mei=Morihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AkaoSatoshi en-aut-sei=Akao en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SomuraHiroaki en-aut-sei=Somura en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanoChiyu en-aut-sei=Nakano en-aut-mei=Chiyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Science and Engineering, Doshisha University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Organization for Research Strategy and Development, Okayama University kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=straw kn-keyword=straw en-keyword=methane mitigation kn-keyword=methane mitigation en-keyword=SMFC kn-keyword=SMFC en-keyword=microorganisms kn-keyword=microorganisms en-keyword=current generation kn-keyword=current generation END start-ver=1.4 cd-journal=joma no-vol=93 cd-vols= no-issue=4 article-no= start-page=335 end-page=343 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Elucidation of Low-temperature Regulated Flavone Synthesis in Dahlia Variabilis and its Effects on Flower Color en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dahlia (Dahlia variabilis) flower colors are diverse and are determined by the accumulation of flavonoids. Cultivars with dark red flowers accumulate more anthocyanins in their petals. Flower color changes such as color fading often occur in some cultivars. In this study, low minimum temperature regulated flower color fading and flavonoid synthesis in dahlia ‘Nessho’ were investigated. The pigment contents and expression levels of flavonoid biosynthesis genes were investigated in detail under several growing environments in which color fading occurs. Flavones accumulate more in color-faded orange flowers than in dark red ray florets. The expression analysis of the anthocyanin synthesis pathway genes indicated that the upregulation of flavone synthase (DvFNS) gene expression correlated with the high accumulation of flavones in color-faded petals. DvFNS expression was also detected in young leaves, and the expression level was higher in winter than in summer. Seasonal changes in DvFNS expression in young leaves significantly correlated with color fading in petals. The change in DvFNS expression in young unexpanded leaves of relatively high-sensitive plants was significantly higher than that of low-sensitive plants before and after treatment under inductive conditions. In conclusion, low-temperature-inducible changes in the flavonoid accumulation in petals was suggested to reflect a change in DvFNS expression occurring in the meristem prior to flower bud formation. This temporal DvFNS expression in young unexpanded leaves of ‘Nessho’ dahlia could be an insight for the selection and breeding of non-color fading plants. en-copyright= kn-copyright= en-aut-name=K. MuthamiaEdna en-aut-sei=K. Muthamia en-aut-mei=Edna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaitoKoji en-aut-sei=Naito en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkadaHiromasa en-aut-sei=Okada en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KarasawaYukino en-aut-sei=Karasawa en-aut-mei=Yukino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikumuraTokuyu en-aut-sei=Kikumura en-aut-mei=Tokuyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NaraTakuya en-aut-sei=Nara en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamauzuYasunori en-aut-sei=Hamauzu en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MotokiKo en-aut-sei=Motoki en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YasubaKen-ichiro en-aut-sei=Yasuba en-aut-mei=Ken-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshidaYuichi en-aut-sei=Yoshida en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KitamuraYoshikuni en-aut-sei=Kitamura en-aut-mei=Yoshikuni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GotoTanjuro en-aut-sei=Goto en-aut-mei=Tanjuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Agriculture, Shinshu University kn-affil= affil-num=4 en-affil=Faculty of Agriculture, Shinshu University kn-affil= affil-num=5 en-affil=Faculty of Agriculture, Shinshu University kn-affil= affil-num=6 en-affil=Faculty of Agriculture, Shinshu University kn-affil= affil-num=7 en-affil=Faculty of Agriculture, Shinshu University kn-affil= affil-num=8 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=12 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=anthocyanin kn-keyword=anthocyanin en-keyword=dahlia kn-keyword=dahlia en-keyword=flavone synthase kn-keyword=flavone synthase en-keyword=seasonal color fading kn-keyword=seasonal color fading en-keyword=young unexpanded leaves kn-keyword=young unexpanded leaves END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=34 article-no= start-page=36114 end-page=36121 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240812 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Engineering Zeolitic-Imidazolate-Framework-Derived Mo-Doped Cobalt Phosphide for Efficient OER Catalysts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Designing a cheap, competent, and durable catalyst for the oxygen evolution reaction (OER) is exceedingly necessary for generating oxygen through a water-splitting reaction. In this project, we have designed a ZIF-67-originated molybdenum-doped cobalt phosphide (CoP) using a simplistic dissolution?regrowth method using Na2MoO4 and a subsequent phosphidation process. This leads to the formation of an exceptional hollow nanocage morphology that is useful for enhanced catalytic activity. Metal?organic frameworks, especially ZIF-67, can be used both as a template and as a metal (cobalt) precursor. Molybdenum-doped CoP was fabricated through a two-step synthesis process, and the fabricated Mo-doped CoP showed excellent catalytic activity during the OER with a lower value of overpotential. Furthermore, the effect of the Mo amount on the catalytic activity has been explored. The best catalyst (CoMoP-2) showed an onset potential of around 1.49 V at 10 mA cm?2 to give rise to a Tafel slope of 62.1 mV dec?1. The improved catalytic activity can be attributed to the increased porosity and surface area of the resultant catalyst. en-copyright= kn-copyright= en-aut-name=RahmanMohammad Atiqur en-aut-sei=Rahman en-aut-mei=Mohammad Atiqur kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=CaiZe en-aut-sei=Cai en-aut-mei=Ze kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoushumyZannatul Mumtarin en-aut-sei=Moushumy en-aut-mei=Zannatul Mumtarin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TagawaRyuta en-aut-sei=Tagawa en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HidakaYoshiharu en-aut-sei=Hidaka en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoChiyu en-aut-sei=Nakano en-aut-mei=Chiyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IslamMd. Saidul en-aut-sei=Islam en-aut-mei=Md. Saidul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SekineYoshihiro en-aut-sei=Sekine en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IdaShintaro en-aut-sei=Ida en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayamiShinya en-aut-sei=Hayami en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Science and Technology, Kumamoto University kn-affil= affil-num=2 en-affil=Department of Chemistry, Graduate School of Science and Technology, Kumamoto University kn-affil= affil-num=3 en-affil=Department of Applied Chemistry and Biochemistry, Graduate School of Science and Technology, Kumamoto University kn-affil= affil-num=4 en-affil=Department of Chemistry, Graduate School of Science and Technology, Kumamoto University kn-affil= affil-num=5 en-affil=Department of Chemistry, Graduate School of Science and Technology, Kumamoto University kn-affil= affil-num=6 en-affil=Research Core for Interdisciplinary Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Chemistry, Graduate School of Science and Technology, Kumamoto University kn-affil= affil-num=8 en-affil=Department of Chemistry, Graduate School of Science and Technology, Kumamoto University kn-affil= affil-num=9 en-affil=Research Core for Interdisciplinary Sciences, Okayama University kn-affil= affil-num=10 en-affil=Institute of Industrial Nanomaterials (IINa), Kumamoto University kn-affil= affil-num=11 en-affil=Institute of Industrial Nanomaterials (IINa), Kumamoto University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=238 cd-vols= no-issue= article-no= start-page=120296 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Grafting-through functionalization of graphene oxide with cationic polymers for enhanced adsorption of anionic dyes and viruses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Graphene oxide (GO) is a sheet-like carbon material with abundant oxygen-containing functional groups on its surface. GO has been extensively studied as an adsorbent for heavy metals and organic compounds. However, effective strategies for negatively charged materials have yet to be established. This study aimed to synthesize composites of GO and cationic polymers for the selective adsorption of negatively charged materials; a challenge in this approach is the strong electrostatic interactions between GO and cationic polymers, which can lead to aggregation. This study addresses this issue by employing the grafting-through method. GO was initially modified with allylamine to introduce a polymerizable site, followed by radical polymerization to covalently bond polymers to the GO surface, effectively preventing aggregation. Adsorption experiments demonstrated that the GO-polymer composite selectively adsorbs anionic dye, such as methyl orange. Virus adsorption tests showed significantly enhanced performance compared to pristine GO. These results emphasize the critical role of controlled surface modification and charge manipulation in optimizing the adsorption performance of GO. This study establishes a simple and effective approach for synthesizing GO-cationic polymer composites, contributing to the development of advanced materials for water purification applications. en-copyright= kn-copyright= en-aut-name=KimuraRyota en-aut-sei=Kimura en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Ferr?-PujolPilar en-aut-sei=Ferr?-Pujol en-aut-mei=Pilar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Core for Interdisciplinary Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Graphene oxide kn-keyword=Graphene oxide en-keyword=Virus adsorption kn-keyword=Virus adsorption en-keyword=Dye adsorption kn-keyword=Dye adsorption en-keyword=Cationic polymer composites kn-keyword=Cationic polymer composites en-keyword=Adsorbent kn-keyword=Adsorbent en-keyword=Aggregation kn-keyword=Aggregation END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=213 end-page=231 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250314 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=RKPM: Restricted Kernel Page Mechanism to?Mitigate Privilege Escalation Attacks en-subtitle= kn-subtitle= en-abstract= kn-abstract=Kernel memory corruption attacks against operating systems exploit kernel vulnerabilities to overwrite kernel data. Kernel address space layout randomization makes it difficult to identify kernel data by randomizing their virtual address space. Control flow integrity (CFI) prevents unauthorized kernel code execution by verifying kernel function calls. However, these countermeasures do not prohibit writing to kernel data. If the virtual address of privileged information is specified and CFI is circumvented, the privileged information can be modified by a kernel memory corruption attack. In this paper, we propose a restricted kernel page mechanism (RKPM) to mitigate kernel memory corruption attacks by introducing restricted kernel pages to protect the kernel data specified in the kernel. The RKPM focuses on the fact that kernel memory corruption attacks attempt to read the virtual addresses around the privileged information. The RKPM adopts page table mapping handling and a memory protection key to control the read and write restrictions of the restricted kernel pages. This allows us to mitigate kernel memory corruption attacks by capturing reads to the restricted kernel page before the privileged information is overwritten. As an evaluation of the RKPM, we confirmed that it can mitigate privilege escalation attacks on the latest Linux kernel. We also measured that there was a certain overhead in the kernel performance. This study enhances kernel security by mitigating privilege escalation attacks through the use of software or hardware based restricted kernel pages. en-copyright= kn-copyright= en-aut-name=KuzunoHiroki en-aut-sei=Kuzuno en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamauchiToshihiro en-aut-sei=Yamauchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Engineering, Kobe University kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=222 end-page=234 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=2023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=vkTracer: Vulnerable Kernel Code Tracing to?Generate Profile of?Kernel Vulnerability en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vulnerable kernel codes are a threat to an operating system kernel. An adversary’s user process can forcefully invoke a vulnerable kernel code to cause privilege escalation or denial of service (DoS). Although service providers or security operators have to determine the effect of kernel vulnerabilities on their environment to decide the kernel updating, the list of vulnerable kernel codes are not provided from the common vulnerabilities and exposures (CVE) report. It is difficult to identify the vulnerable kernel codes from the exploitation result of the kernel which indicates the account information or the kernel suspension. To identify the details of kernel vulnerabilities, this study proposes a vulnerable kernel code tracer (vkTracer), which employs an alternative viewpoint using proof-of-concept (PoC) code to create a profile of kernel vulnerability. vkTracer traces the user process of the PoC code and the running kernel to hook the invocation of the vulnerable kernel codes. Moreover, vkTracer extracts the whole kernel component’s information using the running and static kernel image and debug section. The evaluation results indicated that vkTracer could trace PoC code executions (e.g., privilege escalation and DoS), identify vulnerable kernel codes, and generate kernel vulnerability profiles. Furthermore, the implementation of vkTracer revealed that the identification overhead ranged from 5.2683 s to 5.2728 s on the PoC codes and the acceptable system call latency was 3.7197 μs. en-copyright= kn-copyright= en-aut-name=KuzunoHiroki en-aut-sei=Kuzuno en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamauchiToshihiro en-aut-sei=Yamauchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Engineering, Kobe University kn-affil= affil-num=2 en-affil=Faculty of Natural Science and Technology, Okayama University kn-affil= en-keyword=Kernel vulnerability kn-keyword=Kernel vulnerability en-keyword=Dynamic analysis kn-keyword=Dynamic analysis en-keyword=System security kn-keyword=System security END start-ver=1.4 cd-journal=joma no-vol=57 cd-vols= no-issue=1 article-no= start-page=35 end-page=50 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250724 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A New Approach to Economic Ripple Effects in Regional Input-Output Tables kn-title=地域産業連関表における経済波及効果のNew Approach en-subtitle= kn-subtitle= en-abstract=　This paper first addresses the concept of economic ripple effects, highlighting that simulation results based on input-output tables often lead to overestimations. The primary reason for this overestimation lies in a misunderstanding of the underlying assumptions that generate ripple effects. Specifically, household consumption within a given region merely represents a transfer of money rather than a genuine economic impact. In principle, ripple effects should be understood as additional consumption resulting from increased income. In the absence of income growth, such effects largely represent consumption substitution or intertemporal shifts in spending. Furthermore, what is commonly referred to as “economic impact” is typically calculated as the cumulative total of sales revenue, which aggregates all monetary transactions indiscriminately. This approach differs from the concept of value-added effects, or income effects, which cannot exceed the initial inflow of money from outside the region. One of the factors contributing to these misinterpretations is the insufficient education on input-output analysis at universities. Additionally, computational tools provided by think tanks and public institutions for estimating ripple effects also present methodological issues. To address these challenges, this paper further refines a model previously proposed by the author that visualizes the ripple effect process. The study demonstrates, using real-world examples, the process of constructing ex-post input-output tables following exogenous impacts such as events. In particular, the paper introduces a “partially non-competitive import type” input structure as an alternative to the conventional competitive import-type input-output tables, which tend to overestimate the effects of changes in self-sufficiency rates. This new approach offers a more accurate framework for analyzing economic impacts. kn-abstract=　本稿では，まず経済波及効果の考え方について，産業連関表を用いたシミュレーションの結果が，しばしば過大評価になっていることを述べる。その理由として，経済波及効果をもたらす前提条件の考え方にしばしば誤解があることを指摘する。域内の居住者の消費はマネーの移転であり，真の経済効果ではない。波及効果とは，本来，所得が増えた結果の追加消費であって，所得が増えない状況では，代替消費や消費の先取りに過ぎないのである。また，一般にいう経済効果とは，売上高の積み上げであって同じマネーが何でも加算されているものであり，付加価値効果すなわち所得効果とは異なる。付加価値効果は，当初の域外から入ってきたマネー以上にはならない。こういった解釈の誤謬をもたらしているのは，大学での産業連関分析の教育が十分でないことも原因の1つであるが，シンクタンクや公的機関などで提供されている波及効果の計算ツールにも問題がある。そこで本稿では，これまで筆者が提唱してきた波及効果プロセスを見える化するモデルを更に精緻化し，イベントなど外生的インパクトが発生した後の事後的な産業連関表を構築する流れに関して実例を用いて説明を行う。特に自給率の変化の効果については，これまでの競争移入型連関表では効果が過大傾向になる問題点を解消するべく，「部分非競争移入型」の投入構造を提案し，新たな分析方法を提案する。 en-copyright= kn-copyright= en-aut-name=NakamuraRyohei en-aut-sei=Nakamura en-aut-mei=Ryohei kn-aut-name=中村良平 kn-aut-sei=中村 kn-aut-mei=良平 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=14 article-no= start-page=6927 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250718 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Inhibitory Effects of Vandetanib on Catecholamine Synthesis in Rat Pheochromocytoma PC12 Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gain-of-function gene alterations in rearranged during transfection (RET), a receptor tyrosine kinase, are observed in both sporadic and hereditary medullary thyroid cancers (MTCs) and pheochromocytomas and paragangliomas (PPGLs). Several tyrosine kinase inhibitors (TKIs) that target RET have been proven to be effective on MTCs and PCCs. Recently, TKIs, namely, sunitinib and selpercatinib, which were clinically used to target PPGLs, have been reported to decrease catecholamine levels without reducing tumor size. Our clinical case of metastatic medullary thyroid cancer, which is associated with RET mutations undergoing treatment with vandetanib, also suggests that vandetanib can decrease catecholamine levels. Therefore, we investigated the effect of vandetanib, a representative multi-targeted TKI for RET-related MTC, on cell proliferation and catecholamine synthesis in rat pheochromocytoma PC12 cells. Vandetanib reduced viable cells in a concentration-dependent manner. The dopamine and noradrenaline levels of the cell lysate were reduced in a concentration-dependent manner. They also decreased more prominently at lower concentrations of vandetanib compared to the inhibition of cell proliferation. The RNA knockdown study of Ret revealed that this inhibitory effect on catecholamine synthesis is mainly mediated by the suppression of RET signaling. Next, we focused on two signaling pathways downstream of RET, namely, ERK and AKT signaling. Treatment with vandetanib reduced both ERK and AKT phosphorylation in PC12 cells. Moreover, both an MEK inhibitor U0126 and a PI3K/AKT inhibitor LY294002 suppressed catecholamine synthesis without decreasing viable cells. This study in rat pheochromocytoma PC12 cells reveals the direct inhibitory effects of vandetanib on catecholamine synthesis via the suppression of RET-ERK and RET-AKT signaling. en-copyright= kn-copyright= en-aut-name=ItohYoshihiko en-aut-sei=Itoh en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InagakiKenichi en-aut-sei=Inagaki en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TerasakaTomohiro en-aut-sei=Terasaka en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorimotoEisaku en-aut-sei=Morimoto en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshiiTakahiro en-aut-sei=Ishii en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamaokaKimitomo en-aut-sei=Yamaoka en-aut-mei=Kimitomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujisawaSatoshi en-aut-sei=Fujisawa en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=tyrosine kinase inhibitor kn-keyword=tyrosine kinase inhibitor en-keyword=multiple endocrine neoplasia type 2 kn-keyword=multiple endocrine neoplasia type 2 en-keyword=paraganglioma kn-keyword=paraganglioma en-keyword=RET kn-keyword=RET en-keyword=ERK kn-keyword=ERK en-keyword=AKT kn-keyword=AKT END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=ncaf080 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250718 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Optimizing radiation dose and image quality in neonatal mobile radiography en-subtitle= kn-subtitle= en-abstract= kn-abstract=Children are more susceptible to radiation exposure than adults. Therefore, determining an appropriate radiation dose requires balancing and minimizing radiation exposure while maintaining image quality (IQ) for accurate diagnosis. We evaluated the optimal radiation dose parameters for neonatal chest and abdominal mobile radiography by assessing entrance surface dose and IQ indices. A range of exposure parameters was tested on neonatal and acrylic phantoms, and the optimal settings were determined through visual and physical evaluations. Overall, 65 kVp and 1.2 mAs provided the best balance between minimizing radiation exposure and maintaining high IQ for neonates. This study offers essential insights into optimizing radiographic conditions for neonatal care, contributing to safe and effective radiological practices. These optimized parameters can help guide future clinical applications by ensuring reduced radiation risk and enhanced diagnostic accuracy. en-copyright= kn-copyright= en-aut-name=MaedaTakahiko en-aut-sei=Maeda en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaraMakoto en-aut-sei=Hara en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamasakiHiroyuki en-aut-sei=Yamasaki en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakaharaMakoto en-aut-sei=Nakahara en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanabeYoshinori en-aut-sei=Tanabe en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Health Sciences, Department of Radiological Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiology, Hyogo Prefectural Kobe Children’s Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Hyogo Prefectural Kobe Children’s Hospital kn-affil= affil-num=4 en-affil=Department of Radiology, Hyogo Prefectural Tamba Medical Center kn-affil= affil-num=5 en-affil=Faculty of Medicine, Graduate School of Health Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=637 cd-vols= no-issue=8046 article-no= start-page=744 end-page=748 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Centrophilic retrotransposon integration via CENH3 chromatin in Arabidopsis en-subtitle= kn-subtitle= en-abstract= kn-abstract=In organisms ranging from vertebrates to plants, major components of centromeres are rapidly evolving repeat sequences, such as tandem repeats (TRs) and transposable elements (TEs), which harbour centromere-specific histone H3 (CENH3)1,2. Complete centromere structures recently determined in human and Arabidopsis suggest frequent integration and purging of retrotransposons within the TR regions of centromeres3,4,5. Despite the high impact of ‘centrophilic’ retrotransposons on the paradox of rapid centromere evolution, the mechanisms involved in centromere targeting remain poorly understood in any organism. Here we show that both Ty3 and Ty1 long terminal repeat retrotransposons rapidly turnover within the centromeric TRs of Arabidopsis species. We demonstrate that the Ty1/Copia element Tal1 (Transposon of Arabidopsis lyrata 1) integrates de novo into regions occupied by CENH3 in Arabidopsis thaliana, and that ectopic expansion of the CENH3 region results in spread of Tal1 integration regions. The integration spectra of chimeric TEs reveal the key structural variations responsible for contrasting chromatin-targeting specificities to centromeres versus gene-rich regions, which have recurrently converted during the evolution of these TEs. Our findings show the impact of centromeric chromatin on TE-mediated rapid centromere evolution, with relevance across eukaryotic genomes. en-copyright= kn-copyright= en-aut-name=TsukaharaSayuri en-aut-sei=Tsukahara en-aut-mei=Sayuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BousiosAlexandros en-aut-sei=Bousios en-aut-mei=Alexandros kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Perez-RomanEstela en-aut-sei=Perez-Roman en-aut-mei=Estela kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamaguchiSota en-aut-sei=Yamaguchi en-aut-mei=Sota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LeduqueBasile en-aut-sei=Leduque en-aut-mei=Basile kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoAimi en-aut-sei=Nakano en-aut-mei=Aimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaishMatthew en-aut-sei=Naish en-aut-mei=Matthew kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OsakabeAkihisa en-aut-sei=Osakabe en-aut-mei=Akihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ToyodaAtsushi en-aut-sei=Toyoda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoHidetaka en-aut-sei=Ito en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EderaAlejandro en-aut-sei=Edera en-aut-mei=Alejandro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TominagaSayaka en-aut-sei=Tominaga en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Juliarni en-aut-sei=Juliarni en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatoKae en-aut-sei=Kato en-aut-mei=Kae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OdaShoko en-aut-sei=Oda en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=InagakiSoichi en-aut-sei=Inagaki en-aut-mei=Soichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Lorkovi?Zdravko en-aut-sei=Lorkovi? en-aut-mei=Zdravko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NagakiKiyotaka en-aut-sei=Nagaki en-aut-mei=Kiyotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=BergerFr?d?ric en-aut-sei=Berger en-aut-mei=Fr?d?ric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KawabeAkira en-aut-sei=Kawabe en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=QuadranaLeandro en-aut-sei=Quadrana en-aut-mei=Leandro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HendersonIan en-aut-sei=Henderson en-aut-mei=Ian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KakutaniTetsuji en-aut-sei=Kakutani en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=2 en-affil=School of Life Sciences, University of Sussex kn-affil= affil-num=3 en-affil=School of Life Sciences, University of Sussex kn-affil= affil-num=4 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=5 en-affil=Institute of Plant Sciences Paris‐Saclay (IPS2), Centre National de la Recherche Scientifique, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement, Universit? Evry, Universit? Paris kn-affil= affil-num=6 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Plant Sciences, University of Cambridge kn-affil= affil-num=8 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=9 en-affil=Center for Genetic Resource Information, National Institute of Genetics kn-affil= affil-num=10 en-affil=Faculty of Science, Hokkaido University kn-affil= affil-num=11 en-affil=Institute of Plant Sciences Paris‐Saclay (IPS2), Centre National de la Recherche Scientifique, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement, Universit? Evry, Universit? Paris kn-affil= affil-num=12 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=13 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=14 en-affil=Department of Integrated Genetics, National Institute of Genetics kn-affil= affil-num=15 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=16 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=17 en-affil=Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna BioCenter (VBC) kn-affil= affil-num=18 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=19 en-affil=Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna BioCenter (VBC) kn-affil= affil-num=20 en-affil=Faculty of Life Sciences, Kyoto Sangyo University kn-affil= affil-num=21 en-affil=Institute of Plant Sciences Paris‐Saclay (IPS2), Centre National de la Recherche Scientifique, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement, Universit? Evry, Universit? Paris kn-affil= affil-num=22 en-affil=Department of Plant Sciences, University of Cambridge kn-affil= affil-num=23 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=186 cd-vols= no-issue= article-no= start-page=118030 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=(+)-Terrein exerts anti-obesity and anti-diabetic effects by regulating the differentiation and thermogenesis of brown adipocytes in mice fed a high-fat diet en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: (+)-Terrein, a low-molecular-weight secondary metabolite from Aspergillus terreus, inhibits adipocyte differentiation in vitro. However, the precise mechanisms underlying the effects of (+)-terrein on adipocytes remain unclear. We hypothesized that (+)-terrein modulates adipogenesis and glucose homeostasis in obesity and diabetes via anti-inflammatory action and regulation of adipocyte differentiation. Hence, in this study, we aimed to investigate the in vivo anti-diabetic and anti-obesity effects of (+)-terrein.
Methods: Male C57BL/6?J mice were fed normal chow or high-fat (HF) diet and administered (+)-terrein (180?mg/kg) via intraperitoneal injection. Glucose and insulin tolerance tests, serum biochemical assays, and histological analyses were also performed. Rat brown preadipocytes, mouse brown preadipocytes (T37i cells), and inguinal white adipose tissue (ingWAT) preadipocytes were exposed to (+)-terrein during in vitro adipocyte differentiation. Molecular markers associated with thermogenesis and differentiation were quantified using real-time polymerase chain reaction and western blotting.
Results: (+)-Terrein-treated mice exhibited improved insulin sensitivity and reduced serum lipid and glucose levels, irrespective of the diet. Furthermore, (+)-terrein suppressed body weight gain and mitigated fat accumulation by activating brown adipose tissue in HF-fed mice. (+)-Terrein facilitated the in vitro differentiation of rat brown preadipocytes, T37i cells, and ingWAT preadipocytes by upregulating peroxisome proliferator-activated receptor-γ (PPARγ). This effect was synergistic with that of a PPARγ agonist.
Conclusion: This study demonstrated that (+)-terrein effectively induces PPARγ expression and brown adipocyte differentiation, leading to reduced weight gain and improved glucose and lipid profiles in HF-fed mice. Thus, (+)-terrein is a potent novel agent with potential anti-obesity and anti-diabetic properties. en-copyright= kn-copyright= en-aut-name=Aoki-SaitoHaruka en-aut-sei=Aoki-Saito en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MandaiHiroki en-aut-sei=Mandai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakakuraTakashi en-aut-sei=Nakakura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasakiTsutomu en-aut-sei=Sasaki en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitamuraTadahiro en-aut-sei=Kitamura en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HisadaTakeshi en-aut-sei=Hisada en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkadaShuichi en-aut-sei=Okada en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugaSeiji en-aut-sei=Suga en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaMasanobu en-aut-sei=Yamada en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SaitoTsugumichi en-aut-sei=Saito en-aut-mei=Tsugumichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science kn-affil= affil-num=3 en-affil=Department of Anatomy, Teikyo University School of Medicine kn-affil= affil-num=4 en-affil=Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University kn-affil= affil-num=5 en-affil=Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University kn-affil= affil-num=6 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Gunma University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Department of Diabetes, Soleiyu Asahi Clinic kn-affil= affil-num=9 en-affil=Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University kn-affil= affil-num=10 en-affil=Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Health & Sports Sciences, Faculty of Education, Tokyo Gakugei University kn-affil= en-keyword=(+)-Terrein kn-keyword=(+)-Terrein en-keyword=Brown adipose tissue kn-keyword=Brown adipose tissue en-keyword=Thermogenesis kn-keyword=Thermogenesis en-keyword=Obesity kn-keyword=Obesity en-keyword=PPARγ kn-keyword=PPARγ 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=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=From Carboxylic Acids or Their Derivatives to Amines and Ethers: Modern Decarboxylative Approaches for Sustainable C?N and C?O Bond Formation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Amines and ethers represent essential structural motifs in pharmaceuticals, natural products, organic materials, and catalytic systems. The development of novel, environmentally friendly, and cost-effective strategies for constructing C?N and C?O bonds is therefore of significant importance for the synthesis of these compounds. In recent years, carboxylic acids and their derivatives have emerged as attractive, inexpensive, non-toxic, and readily available synthetic building blocks, serving as promising alternatives to aryl halides. Growing evidence has demonstrated that decarboxylative amination and etherification of carboxylic acid derivatives offer a powerful approach for the synthesis of amines and ethers. These transformations proceed via three principal mechanistic pathways, each offering high atom economy. Specifically, carbanions (or organometallic species) generated through heterolytic decarboxylation can react with suitable electrophiles to form C?heteroatom bonds. In contrast, carbon-centred radicals produced through homolytic decarboxylation can couple with heteroatom-based reagents via radical recombination or oxidative trapping. Additionally, carbocations are typically formed via electrochemical oxidation of carboxylic acids: oxidative decarboxylation first yields a carbon radical, which is then further oxidized at the anode to generate a carbocation. This highly electrophilic intermediate can subsequently be intercepted by heteroatom nucleophiles to construct C?N or C?O bonds. This review highlights recent advances in the field, with a focus on transition metal catalysis, photoredox catalysis, and electrochemical methods for decarboxylative amination and etherification. en-copyright= kn-copyright= en-aut-name=YanWeidan en-aut-sei=Yan en-aut-mei=Weidan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TianTian en-aut-sei=Tian en-aut-mei=Tian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiharaYasushi en-aut-sei=Nishihara en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science (RIIS), Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e00678 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250623 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alkoxy‐Substituted Anthrabis(Thiadiazole)‐Terthiophene Copolymers for Organic Photovoltaics: A Unique Wavy Backbone Enhances Aggregation, Molecular Order, and Device Efficiency en-subtitle= kn-subtitle= en-abstract= kn-abstract=Two polymer donors, PATz3T-o6BO and PATz3T-o6HD, incorporating alkoxy-substituted anthra[1,2-c:5,6-c′]bis([1,2,5]thiadiazole), were strategically designed and synthesized. The unique wavy backbone of these polymers effectively reduced aggregation, leading to enhanced solubility and significantly improved molecular ordering. Consequently, the PATz3T-o6HD:Y12-based solar cells achieved a power conversion efficiency (PCE) of 7.94%. These findings provide valuable insights into the molecular design of high-performance polymer donors for organic photovoltaics (OPVs). en-copyright= kn-copyright= en-aut-name=YanYi en-aut-sei=Yan en-aut-mei=Yi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriHiroki en-aut-sei=Mori en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshinoTomoki en-aut-sei=Yoshino en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InamiRyuki en-aut-sei=Inami en-aut-mei=Ryuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChangJiaxin en-aut-sei=Chang en-aut-mei=Jiaxin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GaoJunqing en-aut-sei=Gao en-aut-mei=Junqing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishiharaYasushi en-aut-sei=Nishihara en-aut-mei=Yasushi 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=Research Institute for Interdisciplinary Science, 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=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=Aggregation kn-keyword=Aggregation en-keyword=Backbone conformation kn-keyword=Backbone conformation en-keyword=Conjugated polymers kn-keyword=Conjugated polymers en-keyword=Organic solar cells kn-keyword=Organic solar cells en-keyword=Semiconducting polymers kn-keyword=Semiconducting polymers END start-ver=1.4 cd-journal=joma no-vol=653 cd-vols= no-issue= article-no= start-page=119205 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Meteoritic and asteroidal amino acid heterogeneity: Implications for planetesimal alteration conditions and sample return missions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Carbonaceous chondrites (CC) and asteroid return samples contain amino acids (AA), which are essential for an origin of life on the early Earth and can provide important information concerning planetesimal alteration processes. While many studies have investigated AA from CC, separate studies have often found differing abundances for the same meteorite. Accordingly, analytical bias, differing terrestrial contamination levels and intrinsic sample heterogeneity have been proposed as potential reasons. However, current analytical techniques allow for the analysis of several mg-sized samples and can thus enable an investigation of AA heterogeneity within single meteorite specimens. Here, such an analytical technique is applied to characterise the AA in triplicate aliquots of three CCs. The results indicate that CCs are heterogenous in terms of their AA at the mm-scale. Furthermore, the results help to further constrain the effects of planetesimal alteration on organic matter and the requirements of future sample return missions that aim to obtain organic-bearing extraterrestrial materials. 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=OtaTsutomu en-aut-sei=Ota en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=5 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=6 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= en-keyword=Carbonaceous chondrite kn-keyword=Carbonaceous chondrite en-keyword=Heterogeneity kn-keyword=Heterogeneity en-keyword=Planetesimal kn-keyword=Planetesimal en-keyword=Aqueous alteration kn-keyword=Aqueous alteration en-keyword=Amino acid and meteorite kn-keyword=Amino acid and meteorite 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=2025 dt-pub=20250603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Amino Acid Substitutions in Loop C of Arabidopsis PIP2 Aquaporins Alters the Permeability of CO2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The transport of CO2 across biomembranes in plant cells is essential for efficient photosynthesis. Some aquaporins capable of CO2 transport, referred to as ‘COOporins’, are postulated to play a crucial role in leaf CO2 diffusion. However, the structural basis of CO2 permeation through aquaporins remains largely unknown. Here, we show that amino acids in loop C are critical for the CO2 permeability of Arabidopsis thaliana PIP2 aquaporins. We found that swapping tyrosine and serine in loop C to histidine and phenylalanine, which differ between AtPIP2;1 and AtPIP2;3, altered CO2 permeability when examined in the Xenopus laevis oocyte heterologous expression system. AlphaFold2 modelling indicated that these substitution induced a conformational shift in the sidechain of arginine in the aromatic/arginine (ar/R) selectivity filter and in lysine at the extracellular mouth of the monomeric pore in PIP2 aquaporins. Our findings demonstrate that distal amino acid substitutions can trigger conformational changes of the ar/R filter in the monomeric pore, modulating CO2 permeability. Additionally, phylogenetic analysis suggested that aquaporins capable of dual water/CO2 permeability are ancestral to those that are water-selective and CO2-impermeable, and CO2-selective and water impermeable. en-copyright= kn-copyright= en-aut-name=TaniaShaila Shermin en-aut-sei=Tania en-aut-mei=Shaila Shermin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TsuchiyaYoshiyuki en-aut-sei=Tsuchiya en-aut-mei=Yoshiyuki 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=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriIzumi C. en-aut-sei=Mori en-aut-mei=Izumi C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Arabidopsis thaliana kn-keyword=Arabidopsis thaliana en-keyword=CO2 transport kn-keyword=CO2 transport en-keyword=monomeric pore kn-keyword=monomeric pore en-keyword=PIP2 aquaporin kn-keyword=PIP2 aquaporin en-keyword=Xenopus laevis kn-keyword=Xenopus laevis END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=23 article-no= start-page=17720 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A meta-linked isomer of ITIC: influence of aggregation patterns on open-circuit voltage in organic solar cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Improving the open-circuit voltage (VOC) of organic solar cells (OSCs) remains an important challenge. While it is known that the energy levels at the donor/acceptor (D/A) interface affect the VOC, the impact of aggregation patterns on the energy levels at the D/A interface has not been fully elucidated. Herein, we focus on ITIC, a widely used acceptor in OSCs, and designed a meta-linked isomer of ITIC (referred to as im-ITIC) to alter molecular symmetry and modify substitution arrangements. Concentration-dependent 1H NMR spectra revealed that im-ITIC shows stronger aggregation behavior in solution. Single-crystal X-ray analysis showed that im-ITIC forms both tail-to-tail (J-aggregation) and face-to-face (H-aggregation) stacking modes, whereas ITIC exclusively forms tail-to-tail stacking. OSCs based on PBDB-T:im-ITIC showed a high VOC value of 1.02 V, which is 0.12 V higher than that of those based on PBDB-T:ITIC. Time-resolved infrared measurements revealed the lifetime of free electrons for the pristine and blend films. The energy levels of the charge transfer state (ECT) for PBDB-T:im-ITIC- and PBDB-T:ITIC OSCs were determined to be 1.57 and 1.39 eV, respectively, correlating with the VOC values. Theoretical calculations indicated that pronounced H-aggregation in im-ITIC increases the ECT compared with J-aggregation, contributing to the improved VOC. This study underscores the critical impact of molecular aggregation patterns on energy alignment and VOC enhancement, offering insights into molecular design for achieving high VOC in OSCs. en-copyright= kn-copyright= en-aut-name=WangKai en-aut-sei=Wang en-aut-mei=Kai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=JinnaiSeihou en-aut-sei=Jinnai en-aut-mei=Seihou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UesakaKaito en-aut-sei=Uesaka en-aut-mei=Kaito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=IeYutaka en-aut-sei=Ie en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=The Institute of Scientific and Industrial Research (SANKEN), The University of Osaka kn-affil= affil-num=2 en-affil=The Institute of Scientific and Industrial Research (SANKEN), The University of Osaka kn-affil= affil-num=3 en-affil=Graduate School of Natural Science & Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science & Technology, Okayama University kn-affil= affil-num=5 en-affil=The Institute of Scientific and Industrial Research (SANKEN), The University of Osaka kn-affil= END start-ver=1.4 cd-journal=joma no-vol=158 cd-vols= no-issue= article-no= start-page=107932 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trends in nontuberculous mycobacterial disease mortality based on 2000-2022 data from 83 countries en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To examine the international trends for nontuberculous mycobacterial-associated mortality rates, as nontuberculous mycobacterial infections are becoming increasingly prevalent and pose a significant public health challenge, especially in older populations.
Methods: This retrospective observational study used data from the World Health Organization mortality database, which included patients with nontuberculous mycobacterial infection in 83 countries. We stratified the data by sex, age, and geographic region and calculated crude and age-standardized mortality rates to estimate long-term mortality trends.
Results: In total, 42,182 nontuberculous mycobacterial infection-associated deaths (58.1% in women) were reported in 83 countries between 2000 and 2022. The locally weighted regression model estimation for the nontuberculous mycobacterial infection-associated mortality rate more than doubled?from 0.36 deaths per 1000,000 individuals in 2000 to 0.77 deaths per 1000,000 individuals in 2022. Eighty-six percent of nontuberculous mycobacterial infection-associated deaths occurred in people aged ?65 years. The mortality rate was the highest in the Western Pacific Region.
Conclusion: This study highlights the impact of emerging nontuberculous mycobacterial diseases and the importance of targeted interventions for managing and reducing mortality, particularly in vulnerable older populations. Further studies are warranted to determine the factors contributing to geographical disparity and treatment options. en-copyright= kn-copyright= en-aut-name=HaradaKo en-aut-sei=Harada en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=VuQuynh Thi en-aut-sei=Vu en-aut-mei=Quynh Thi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=MinatoYusuke en-aut-sei=Minato en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro 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=Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=2 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Hematology/Oncology, Mayo Clinic kn-affil= affil-num=4 en-affil=Department of Education and Research Centre for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Center for Infectious Disease Research, Fujita Health University kn-affil= affil-num=7 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Population surveillance kn-keyword=Population surveillance en-keyword=Mortality kn-keyword=Mortality en-keyword=Nontuberculous mycobacterial infections kn-keyword=Nontuberculous mycobacterial infections END start-ver=1.4 cd-journal=joma no-vol=262 cd-vols= no-issue=2 article-no= start-page=385 end-page=395 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Analysis of the effect of permeant solutes on the hydraulic resistance of the plasma membrane in cells of Chara corallina en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the cells of Chara corallina, permeant monohydric alcohols including methanol, ethanol and 1-propanol increased the hydraulic resistance of the membrane (Lpm?1). We found that the relative value of the hydraulic resistance (rLpm?1) was linearly dependent on the concentration (Cs) of the alcohol. The relationship is expressed in the equation: rLpm?1?=?ρmCs?+?1, where ρm is the hydraulic resistance modifier coefficient of the membrane. Ye et al. (2004) showed that membrane-permeant glycol ethers also increased Lp?1. We used their data to estimate Lpm?1 and rLpm?1. The values of rLpm?1 fit the above relation we found for alcohols. When we plotted the ρm values of all the permeant alcohols and glycol ethers against their molecular weights (MW), we obtained a linear curve with a slope of 0.014 M?1/MW and with a correlation coefficient of 0.99. We analyzed the influence of the permeant solutes on the relative hydraulic resistance of the membrane (rLpm?1) as a function of the external (π0) and internal (πi) osmotic pressures. The analysis showed that the hydraulic resistance modifier coefficients (ρm) were linearly related to the MW of the permeant solutes with a slope of 0.012 M?1/MW and with a correlation coefficient of 0.84. The linear relationship between the effects of permeating solutes on the hydraulic resistance modifier coefficient (ρm) and the MW can be explained in terms of the effect of the effective osmotic pressure on the hydraulic conductivity of water channels. The result of the analysis suggests that the osmotic pressure and not the size of the permeant solute as proposed by (Ye et al., J Exp Bot 55:449?461, 2004) is the decisive factor in a solute’s influence on hydraulic conductivity. Thus, characean water channels (aquaporins) respond to permeant solutes with essentially the same mechanism as to impermeant solutes. en-copyright= kn-copyright= en-aut-name=TazawaMasashi en-aut-sei=Tazawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WayneRandy en-aut-sei=Wayne en-aut-mei=Randy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= affil-num=1 en-affil=Yoshida Biological Laboratory kn-affil= affil-num=2 en-affil=Laboratory of Natural Philosophy, Plant Biology Section, Cornell University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= en-keyword=Chara corallina kn-keyword=Chara corallina en-keyword=Effective osmotic pressure kn-keyword=Effective osmotic pressure en-keyword=Hydraulic resistance kn-keyword=Hydraulic resistance en-keyword=Plasma membrane kn-keyword=Plasma membrane en-keyword=Reflection coefficient kn-keyword=Reflection coefficient END start-ver=1.4 cd-journal=joma no-vol=169 cd-vols= no-issue= article-no= start-page=155745 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recent progress on phenothiazine organophotoredox catalysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photoredox catalysis has garnered significant attention in recent years due to its broad applicability in visible-light-induced organic transformations. While significant progress has been made in the development of highly oxidizing catalysts, such as acridinium catalysts, there remains a notable shortage of strongly reducing organophotoredox catalysts. Phenothiazines are widely used as photoredox catalysts owing to their unique redox potentials, particularly their low excited-state oxidation potentials (Eox* = ?1.35 V to ?3.51 V vs. SCE). Thus, they can be applied to a variety of photoredox reactions with oxidative-quenching cycles, and effectively reduce various organic molecules, such as aryl and alkyl halides, alkenes, malonyl peroxides, cobalt complexes, and redox-active esters. Due to their unique properties, this review focuses on the recent advances in phenothiazine organophotoredox catalysis. en-copyright= kn-copyright= en-aut-name=TanakaKenta en-aut-sei=Tanaka en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakamuraHiroyoshi en-aut-sei=Takamura en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KadotaIsao en-aut-sei=Kadota en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=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= en-keyword=Phenothiazine kn-keyword=Phenothiazine en-keyword=Photoredox catalysis kn-keyword=Photoredox catalysis en-keyword=Visible light kn-keyword=Visible light en-keyword=Radical kn-keyword=Radical END start-ver=1.4 cd-journal=joma no-vol=599 cd-vols= no-issue=13 article-no= start-page=1914 end-page=1924 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250525 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characterization of molecular mechanisms of CaMKKα/1 oligomerization en-subtitle= kn-subtitle= en-abstract= kn-abstract=Calcium/calmodulin-dependent protein kinase kinase (CaMKK) is an activating kinase for calcium/calmodulin-dependent protein kinase type 1 (CaMKI), calcium/calmodulin-dependent protein kinase type IV (CaMKIV), RAC-alpha serine/threonine-protein kinase (PKB), and AMP-activated protein kinase (AMPK) that has been reported to form an active oligomer in cells. Glutathione S-transferase (GST) pulldown assay from the extracts of COS-7 cells expressing GST- and His6-CaMKKα/1 mutants showed that the C-terminal region containing the autoinhibitory and calmodulin (CaM)-binding sequence (residues 438?463) is required for CaMKKα/1 homo-oligomerization. This was confirmed by the fact that the GST-CaMKKα/1 C-terminal domain (residues 435?505) directly interacted with EGFP-CaMKKα/1 residues 435?505 as well as with wild-type CaMKKα/1. Notably, once oligomerized in cells, CaMKKα/1 is neither exchangeable between the oligomeric complexes nor dissociated by Ca2+/CaM binding. These results support stable oligomerization of CaMKK in the cells by intermolecular self-association of its C-terminal region containing a regulatory domain. en-copyright= kn-copyright= en-aut-name=UenoyamaShun en-aut-sei=Uenoyama en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NittaHayato en-aut-sei=Nitta en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhtsukaSatomi en-aut-sei=Ohtsuka en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MagariMasaki en-aut-sei=Magari en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuizuFutoshi en-aut-sei=Suizu en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TokumitsuHiroshi en-aut-sei=Tokumitsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=3 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Medical Technology, Kagawa Prefectural University of Health Sciences kn-affil= affil-num=6 en-affil= kn-affil= en-keyword=calmodulin kn-keyword=calmodulin en-keyword=calmodulin-kinase cascade kn-keyword=calmodulin-kinase cascade en-keyword=CaMKKa/ kn-keyword=CaMKKa/ en-keyword=oligomerization kn-keyword=oligomerization en-keyword=protein?protein interaction kn-keyword=protein?protein interaction en-keyword=regulatory domain kn-keyword=regulatory domain END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=5 article-no= start-page=705 end-page=721 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SHORT AND CROOKED AWN, encoding the epigenetic regulator EMF1, promotes barley awn development en-subtitle= kn-subtitle= en-abstract= kn-abstract=The awn is a bristle-like extension from the tip of the lemma in grasses. In barley, the predominant cultivars possess long awns that contribute to grain yield and quality through photosynthesis. In addition, various awn morphological mutants are available in barley, rendering it a useful cereal crop to investigate the mechanims of awn development. Here, we identified the gene causative of the short and crooked awn (sca) mutant, which exhibits a short and curved awn phenotype. Intercrossing experiments revealed that the sca mutant induced in the Japanese cultivar (cv.) “Akashinriki” is allelic to the independently isolated moderately short-awn mutant breviaristatum-a (ari-a). Map-based cloning and sequencing revealed that SCA encodes the Polycomb group?associated protein EMBRYONIC FLOWER 1. We found that SCA affects awn development through the promotion of cell proliferation, elongation, and cell wall synthesis. RNA sequencing of cv. Bowman backcross-derived near-isogenic lines of sca and ari-a6 alleles showed that SCA is directly or indirectly involved in promoting the expression of genes related to awn development. Additionally, SCA represses various transcription factors essential for floral organ development and plant architecture, such as MADS-box and Knotted1-like homeobox genes. Notably, the repression of the C-class MADS-box gene HvMADS58 by SCA in awns is associated with the accumulation of the repressive histone modification H3K27me3. These findings highlight the potential role of SCA-mediated gene regulation, including histone modification, as a novel pathway in barley awn development. en-copyright= kn-copyright= en-aut-name=NakamuraKoki en-aut-sei=Nakamura en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikuchiYuichi en-aut-sei=Kikuchi en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShiragaMizuho en-aut-sei=Shiraga en-aut-mei=Mizuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KotakeToshihisa en-aut-sei=Kotake en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HyodoKiwamu en-aut-sei=Hyodo en-aut-mei=Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TaketaShin en-aut-sei=Taketa en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkedaYoko en-aut-sei=Ikeda en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=Graduate School of Science and Engineering, Saitama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=barley kn-keyword=barley en-keyword=awn development kn-keyword=awn development en-keyword=EMBRYONIC FLOWER 1 (EMF1) kn-keyword=EMBRYONIC FLOWER 1 (EMF1) en-keyword=homeotic genes kn-keyword=homeotic genes en-keyword=H3K27 trimethylation kn-keyword=H3K27 trimethylation en-keyword=epigenetic regulation kn-keyword=epigenetic regulation 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=2025 dt-pub=20250710 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tumor Microvessels with Specific Morphology as a Prognostic Factor in Esophageal Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Angiogenesis is essential for tumor progression. Microvessel density (MVD) is a widely used histological method to assess angiogenesis using immunostained sections, but its prognostic significance in esophageal cancer remains controversial. Recently, the evaluation of microvascular architecture has gained importance as a method to assess tumor aggressiveness. The present study aimed to identify the histological characteristics of tumor microvessels that are associated with the aggressiveness of esophageal squamous cell carcinoma.
Patients and Methods A total of 108 esophageal squamous cell carcinoma tissues were immunohistochemically stained with blood vessel markers and angiogenesis-related markers, including CD31, alpha smooth muscle actin, vascular endothelial growth factor A (VEGF-A), CD206, and D2-40. MVD, microvessel pericyte coverage index (MPI), and tumor vascular morphology were evaluated by microscopy.
Results MVD was significantly associated with patient outcomes, whereas neither MPI nor VEGF-A expression throughout the tumor showed a significant correlation. In addition, the presence of blood vessels encircling clusters of tumor cells, termed C-shaped microvessels, and excessively branching microvessels, termed X-shaped microvessels, was significantly associated with poor prognosis. These vessel types were also correlated with clinicopathological parameters, including deeper invasion of the primary tumor, presence of lymph node metastasis, advanced pathological stage, and distant metastasis. Focal VEGF-A immunoexpression in tumor cells was higher in areas containing C-shaped or X-shaped microvessels compared with areas lacking these vessel morphologies.
Conclusions The data suggest that tumor microvessels with specific morphologies (C-shaped and X-shaped microvessels) may serve as a promising prognostic factor in esophageal squamous cell carcinoma. en-copyright= kn-copyright= en-aut-name=TunHnin Thida en-aut-sei=Tun en-aut-mei=Hnin Thida kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraSeitaro en-aut-sei=Nishimura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunitomoTomoyoshi en-aut-sei=Kunitomo en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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 Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Esophageal neoplasms kn-keyword=Esophageal neoplasms en-keyword=Angiogenesis kn-keyword=Angiogenesis en-keyword=Microvessel density kn-keyword=Microvessel density en-keyword=Pericytes kn-keyword=Pericytes en-keyword=VEGF-A kn-keyword=VEGF-A en-keyword=Immunohistochemistry kn-keyword=Immunohistochemistry en-keyword=Prognosis kn-keyword=Prognosis END start-ver=1.4 cd-journal=joma no-vol=177 cd-vols= no-issue=4 article-no= start-page=e70396 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CNGC2 Negatively Regulates Stomatal Closure and Is Not Required for flg22- and H2O2-Induced Guard Cell [Ca2+]cyt Elevation in Arabidopsis thaliana en-subtitle= kn-subtitle= en-abstract= kn-abstract=In guard cells, cytosolic Ca2+ acts as a second messenger that mediates abscisic acid (ABA)- and pathogen-associated molecular pattern (PAMP)-induced stomatal closure. It was reported that Arabidopsis cyclic nucleotide-gated ion channel 2 (CNGC2) functions as hydrogen peroxide (H2O2)- and PAMP-activated Ca2+-permeable channels at the plasma membrane of mesophyll cells and mediates Ca2+-dependent PAMP-triggered immunity. In this study, we examined the role of CNGC2 in the regulation of stomatal movement because CNGC2 is also expressed in guard cells. We found that stomata of the CNGC2 disruption mutant cngc2-3 are constitutively closed even in the absence of ABA or the flagellar-derived PAMP, flg22. Consistently, leaf temperatures of the cngc2-3 mutant were higher than those of wild-type (WT) plants. The stomatal phenotype of the cngc2-3 mutant was restored by complementation with wild-type CNGC2 under the control of the guard cell preferential promoter, pGC1. Elevation of cytosolic free Ca2+ concentration in guard cells induced by flg22 and H2O2 remained intact in the cngc2-3 mutant. The introduction of the ost1-3 mutation into the cngc2-3 background did not alter the stomatal phenotype. However, the stomatal phenotype of the cngc2-3 mutant was successfully rescued in the double disruption mutant cngc2-3aba2-2. Taken together, these results suggest that CNGC2 negatively regulates stomatal closure response and does not function as flg22? and H2O2-activated Ca2+ channels in guard cells. Though CNGC2 is responsive for H2O2- and flg22-induced [Ca2+]cyt elevation in mesophyll cells, the involvement of CNGC2 in the response to H2O2 and flg22 in guard cells is questionable. en-copyright= kn-copyright= en-aut-name=AkterRojina en-aut-sei=Akter en-aut-mei=Rojina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueYasuhiro en-aut-sei=Inoue en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MasumotoSaori en-aut-sei=Masumoto en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MimataYoshiharu en-aut-sei=Mimata en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuuraTakakazu en-aut-sei=Matsuura en-aut-mei=Takakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriIzumi C. en-aut-sei=Mori en-aut-mei=Izumi C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraToshiyuki en-aut-sei=Nakamura en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraYoshimasa en-aut-sei=Nakamura en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MurataYoshiyuki en-aut-sei=Murata en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MunemasaShintaro en-aut-sei=Munemasa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Agriculture, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil= kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=calcium signaling kn-keyword=calcium signaling en-keyword=CNGC kn-keyword=CNGC en-keyword=stomata kn-keyword=stomata END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=13 article-no= start-page=9595 end-page=9603 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250616 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Microagglomerate of VO2 Particles Packing Paraffin Wax Using Capillary Force as a Latent Thermal Energy Storage Medium en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study proposed a material to retain paraffin wax with vanadium dioxide (VO2) particles as a latent thermal energy storage medium, an alternative to core?shell microcapsules containing phase change materials. VO2 microparticles, which were synthesized through a sol?gel method and annealing process, were dispersed in the oil-in-water microemulsion to obtain microagglomerates of VO2 microparticles. The average diameter of microagglomerates was 5 μm, and they retained paraffin wax at the vacancies among VO2 particles. Although the microagglomerates had no complete shells similar to core?shell microcapsules, the microagglomerates successfully trapped paraffin wax droplets without any leakage even in a high-temperature environment. It was because capillary forces acting among VO2 particles strictly prevented any leakage of paraffin waxes. The differential scanning calorimetry revealed that the microagglomerates contained only 16.5 wt % of n-octadecane, used as a paraffin wax. However, since VO2 particles can release or absorb latent heat due to their metal?insulator phase transition, the proposed microagglomerates exhibited higher thermal energy storage densities than phase change microcapsules whose shells do not show phase transitions. Moreover, the microagglomerates exhibited higher thermal conductivity than microcapsules with amorphous inorganic shells because the VO2 particles were crystallized through annealing. The proposed microagglomerate is a promising form for further improving the thermal energy storage density and thermal performance of the latent thermal energy storage medium, especially in the temperature range of 30 to 70 °C. en-copyright= kn-copyright= en-aut-name=IsobeKazuma en-aut-sei=Isobe en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamauchiKaketo en-aut-sei=Yamauchi en-aut-mei=Kaketo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaYutaka en-aut-sei=Yamada en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HoribeAkihiko en-aut-sei=Horibe en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=microagglomerate kn-keyword=microagglomerate en-keyword=vanadium dioxide kn-keyword=vanadium dioxide en-keyword=paraffin wax kn-keyword=paraffin wax en-keyword=latent thermal energy storage medium kn-keyword=latent thermal energy storage medium en-keyword=capillary force kn-keyword=capillary force en-keyword=thermal energy storage density kn-keyword=thermal energy storage density en-keyword=thermal conductivity kn-keyword=thermal conductivity END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=26 article-no= start-page=12024 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Collective motions in the primary coordination sphere: a critical functional framework for catalytic activity of the oxygen-evolving complex of photosystem II en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosynthetic water oxidation, vital for dioxygen production and light energy conversion, is catalyzed by the oxygen-evolving complex of photosystem II, where the inorganic Mn4CaO5 cluster acts as the catalytic core. In this study, we investigate the functional significance of collective motions of amino acid side chains within the primary coordination sphere of the Mn cluster, focusing on their role in modulating the energetic demands for catalytic transformations in the S3 state. We applied regularized canonical correlation analysis to quantitatively correlate the three-dimensional arrangement of coordinating atoms with catalytic driving forces computed via density functional theory. Our analysis reveals that distinct collective side chain motions profoundly influence the energetic requirements for structural reconfigurations of the Mn cluster, achieved through expansion and contraction of the ligand cavity while fine-tuning its geometry to stabilize key intermediates. Complementary predictions from a neural network-based machine learning model indicate that the coordination sphere exerts a variable energetic impact on the catalytic transformations of the Mn cluster, depending on the S-state environment. Integrated computational analyses suggest that the extended lifetime of the S3YZ? state, consistently observed after three flash illuminations, may result from slow, progressive protein dynamics that continuously reshape the energy landscape, thereby shifting the equilibrium positions of rapid, reversible chemical processes over time. Overall, our findings demonstrate that collective motions in the primary coordination sphere constitute an active, dynamic framework essential for the efficient execution of multi-electron catalysis under ambient conditions, while simultaneously achieving a high selectivity with irreversible nature required for effective 3O2 evolution. en-copyright= kn-copyright= en-aut-name=IsobeHiroshi en-aut-sei=Isobe en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiTakayoshi en-aut-sei=Suzuki en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugaMichihiro en-aut-sei=Suga en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamaguchiKizashi en-aut-sei=Yamaguchi en-aut-mei=Kizashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=5 en-affil=Center for Quantum Information and Quantum Biology, Osaka University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=2 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of temperature cycles on the sleep-like state in Hydra vulgaris en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Sleep is a conserved physiological phenomenon across species. It is mainly controlled by two processes: a circadian clock that regulates the timing of sleep and a homeostat that regulates the sleep drive. Even cnidarians, such as Hydra and jellyfish, which lack a brain, display sleep-like states. However, the manner in which environmental cues affect sleep-like states in these organisms remains unknown. In the present study, we investigated the effects of light and temperature cycles on the sleep-like state in Hydra vulgaris.
Results Our findings indicate that Hydra responds to temperature cycles with a difference of up to 5° C, resulting in decreased sleep duration under light conditions and increased sleep duration in dark conditions. Furthermore, our results reveal that Hydra prioritizes temperature changes over light as an environmental cue. Additionally, our body resection experiments show tissue-specific responsiveness in the generation ofthe sleep-like state under different environmental cues. Specifically, the upper body can generate the sleep-like state in response to a single environmental cue. In contrast, the lower body did not respond to 12-h light?dark cycles at a constant temperature.
Conclusions These findings indicate that both light and temperature influence the regulation of the sleep-like state in Hydra. Moreover, these observations highlight the existence of distinct regulatory mechanisms that govern patterns of the sleep-like state in brainless organisms, suggesting the potential involvement of specific regions for responsiveness of environmental cues for regulation of the sleep-like state. en-copyright= kn-copyright= en-aut-name=SatoAya en-aut-sei=Sato en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SekiguchiManabu en-aut-sei=Sekiguchi en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakadaKoga en-aut-sei=Nakada en-aut-mei=Koga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshiiTaishi en-aut-sei=Yoshii en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItohTaichi Q. en-aut-sei=Itoh en-aut-mei=Taichi Q. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Faculty of Arts and Science, Kyushu University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Systems Life Sciences, Kyushu University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Arts and Science, Kyushu University kn-affil= en-keyword=Hydra kn-keyword=Hydra en-keyword=Sleep kn-keyword=Sleep en-keyword=Temperature kn-keyword=Temperature en-keyword=Environmental cues kn-keyword=Environmental cues END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=10819 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster en-subtitle= kn-subtitle= en-abstract= kn-abstract=Protein is essential for all living organisms; however, excessive protein intake can have adverse effects, such as hyperammonemia. Although mechanisms responding to protein deficiency are well-studied, there is a significant gap in our understanding of how organisms adaptively suppress excessive protein intake. In the present study, utilizing the fruit fly, Drosophila melanogaster, we discover that the peptide hormone CCHamide1 (CCHa1), secreted by enteroendocrine cells in response to a high-protein diet (HPD), is vital for suppressing overconsumption of protein. Gut-derived CCHa1 is received by a small subset of enteric neurons that produce short neuropeptide F, thereby modulating protein-specific satiety. Importantly, impairment of the CCHa1-mediated gut-enteric neuronal axis results in ammonia accumulation and a shortened lifespan under HPD conditions. Collectively, our findings unravel the crosstalk of gut hormone and neuronal pathways that orchestrate physiological responses to prevent and adapt to dietary protein overload. en-copyright= kn-copyright= en-aut-name=YoshinariYuto en-aut-sei=Yoshinari en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraTakashi en-aut-sei=Nishimura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=KondoShu en-aut-sei=Kondo en-aut-mei=Shu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanimotoHiromu en-aut-sei=Tanimoto en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiTomoe en-aut-sei=Kobayashi en-aut-mei=Tomoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuyamaMakoto en-aut-sei=Matsuyama en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NiwaRyusuke en-aut-sei=Niwa en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Metabolic Regulation and Genetics, Institute for Molecular and Cellular Regulation, Gunma University kn-affil= affil-num=2 en-affil=Metabolic Regulation and Genetics, Institute for Molecular and Cellular Regulation, Gunma 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=Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science kn-affil= affil-num=5 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=6 en-affil=Division of Molecular Genetics, Shigei Medical Research Institute kn-affil= affil-num=7 en-affil=Division of Molecular Genetics, Shigei Medical Research Institute kn-affil= affil-num=8 en-affil=Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba kn-affil= END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=7 article-no= start-page=1073 end-page=1082 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250520 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Direct insertion of an ion channel immobilized on a soft agarose gel bead into a lipid bilayer: an optimized method en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this paper, we report the development of a device that improves the conventional artificial lipid bilayer method and can measure channel currents more efficiently. Ion channel proteins are an attractive research target in biophysics, because their functions can be measured at the single-molecule level with high time resolution. In addition, they have attracted attention as targets for drug discovery because of their crucial roles in vivo. Although electrophysiological methods are powerful tools for studying channel proteins, they suffer from low measurement efficiency and require considerable skill. In our previous paper, we reported that by immobilizing channel proteins on agarose gel beads and forming an artificial lipid bilayer on the bead surface, we simultaneously solved two problems that had been hindering the efficiency of the artificial bilayer method: the time-consuming formation of artificial lipid bilayers and the time-consuming incorporation of channels into artificial bilayers. Previous studies have utilized crosslinked hard beads; however, here we show that channel current measurement can be achieved more simply and efficiently using non-crosslinked soft beads. In this study, we detailed the process of immobilizing channel proteins on the surface of non-crosslinked beads through chemical modification, allowing us to measure their channel activity. This method enables current measurements without the need for stringent bead size selection or high negative pressure. en-copyright= kn-copyright= en-aut-name=AsakuraMami en-aut-sei=Asakura en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangShuyan en-aut-sei=Wang en-aut-mei=Shuyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiranoMinako en-aut-sei=Hirano en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IdeToru en-aut-sei=Ide en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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= en-keyword=Ion channel kn-keyword=Ion channel en-keyword=Artificial lipid bilayer kn-keyword=Artificial lipid bilayer en-keyword=Suction fixation kn-keyword=Suction fixation en-keyword=Soft agarose bead kn-keyword=Soft agarose bead en-keyword=Current recording kn-keyword=Current recording END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=5 article-no= start-page=489 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mutagenesis Targeting the S153 Residue Within the Transmembrane β-Hairpin of Mosquito-Larvicidal Mpp46Ab Affects Its Toxicity and the Synergistic Toxicity with Cry4Aa en-subtitle= kn-subtitle= en-abstract= kn-abstract=We constructed a library of Mpp46Ab mutants, in which S153 within the transmembrane β-hairpin was randomly replaced by other amino acids. Mutagenesis and subsequent primary screening yielded 10 different Mpp46Ab mutants in addition to the wild type. Remarkably, S153 was replaced with a more hydrophobic amino acid in most of the mutants, and the S153I mutant in particular exhibited significantly increased toxicity. Electrophysiologic analysis using artificial lipid bilayers revealed that the single-channel conductance and PK/PCl permeability ratio were significantly increased for S153I pores. This suggests that the formation of highly ion-permeable and highly cation-selective toxin pores increases the influx of cations and water into cells, thereby facilitating osmotic shock. In addition, the S153F, S153L, and S153I mutants exhibited significantly reduced synergistic toxicity with Cry4Aa. Electrophysiologic analysis showed that the S153F, S153L, and S153I mutants form toxin pores with a significantly reduced PK/PNa permeability ratio and a significantly increased PK/PCa permeability ratio compared to wild-type pores. Thus, our results suggest that pore formation is central to the insecticidal activity of Mpp46Ab and that the ion permeability of toxin pores is a potential indicator correlated with both toxicity and synergistic toxicity with other toxins. en-copyright= kn-copyright= en-aut-name=HayakawaTohru en-aut-sei=Hayakawa en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamaokaSyun en-aut-sei=Yamaoka en-aut-mei=Syun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsakuraMami en-aut-sei=Asakura en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiranoMinako en-aut-sei=Hirano en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IdeToru en-aut-sei=Ide en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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= en-keyword=Bacillus thuringiensis kn-keyword=Bacillus thuringiensis en-keyword=mosquito-larvicidal proteins kn-keyword=mosquito-larvicidal proteins en-keyword=synergistic toxicity kn-keyword=synergistic toxicity en-keyword=Culex pipiens mosquito larvae kn-keyword=Culex pipiens mosquito larvae en-keyword=side-directed mutagenesis kn-keyword=side-directed mutagenesis en-keyword=electrophysiologic analysis kn-keyword=electrophysiologic analysis END start-ver=1.4 cd-journal=joma no-vol=297 cd-vols= no-issue= article-no= start-page=128540 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=Microfluidic paper-based analytical devices for antioxidant vitamins C and E in foods en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this study, we developed microfluidic paper-based analytical devices (μPADs) for the determination of antioxidant vitamins. The proposed μPADs utilize the reduction of metal ions by hydrophilic and hydrophobic antioxidant vitamins, which is followed by colorimetric reactions with chelating reagents. Hydrophilic vitamin C reduces Fe(III) to Fe(II) and forms a stable Fe(II)-bathophenanthroline complex in an aqueous solution. By contrast, this complex is unstable in organic solvents, and hydrophobic vitamin E requires Fe(III) and bathophenanthroline to be replaced with Cu(II) and bathocuproine. In these results, the relationship between the logarithm of a vitamin's concentration and its color intensity was linear and ranged from 4.4 to 35 mg L?1 for ascorbic acid and 50?200 mg L?1 for α-tocopherol. The limits of detection, estimated from the standard deviation of blank samples, were 3.1 mg L?1 for ascorbic acid and either 27 mg L?1 (in hexane) or 48 mg L?1 (in ethanol) for α-tocopherol. The proposed method was used to quantify vitamin C in bell peppers, mandarin oranges, kiwifruit, and lemons, as well as vitamin E in almonds, almond milk, and dietary supplements. The results demonstrate the effectiveness of these μPADs for the practical analysis of antioxidant vitamins in food samples. en-copyright= kn-copyright= en-aut-name=KawaharaMana en-aut-sei=Kawahara en-aut-mei=Mana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DanchanaKaewta en-aut-sei=Danchana en-aut-mei=Kaewta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanetaTakashi en-aut-sei=Kaneta en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Chemistry, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry, Okayama University kn-affil= en-keyword=Microfluidic paper-based analytical device kn-keyword=Microfluidic paper-based analytical device en-keyword=Vitamin C kn-keyword=Vitamin C en-keyword=Vitamin E kn-keyword=Vitamin E en-keyword=Antioxidant vitamin kn-keyword=Antioxidant vitamin en-keyword=Metal complex kn-keyword=Metal complex 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=2025 dt-pub=20250418 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Innovations in paper-based analytical devices and portable absorption photometers for onsite analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Two types of analytical instruments and devices?one sophisticated high-performance instrument and another portable device?have been the focus of recent trends in analytical science. The necessity of point-of-care testing and onsite analysis has accelerated the advancement of high-performance, user-friendly portable analytical devices such as paper-based analytical devices (PADs) and light-emitting diode-based portable photometers. In this review, we summarize our achievements in the study of PADs and portable photometers. Several types of PADs are capable of performing titrations, metal ion analysis, and food analysis, while photometers, which consist of paired emitter?detector light-emitting diode (PEDD) photometers, are used for thiocyanate and herbicide analysis. These PADs and photometers permit the onsite determination of real environmental, body fluid, and food samples when an equipped laboratory is unavailable. en-copyright= kn-copyright= en-aut-name=SeetasangSasikarn en-aut-sei=Seetasang en-aut-mei=Sasikarn kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UmedaMika I. en-aut-sei=Umeda en-aut-mei=Mika I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RenJianchao en-aut-sei=Ren en-aut-mei=Jianchao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanetaTakashi en-aut-sei=Kaneta en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Chemistry, Faculty of Science and Technology, Thammasat University kn-affil= affil-num=2 en-affil=Department of Chemistry, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry, Okayama University kn-affil= affil-num=4 en-affil=Department of Chemistry, Okayama University kn-affil= en-keyword=Point-of-care testing kn-keyword=Point-of-care testing en-keyword=Onsite analysis kn-keyword=Onsite analysis en-keyword=Paper-based analytical device kn-keyword=Paper-based analytical device en-keyword=Paired emitter?detector light-emitting diode kn-keyword=Paired emitter?detector light-emitting diode en-keyword=Photometer kn-keyword=Photometer en-keyword=Environmental analysis kn-keyword=Environmental analysis en-keyword=Food analysis kn-keyword=Food analysis END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=100242 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=Photochemical internalization of mRNA using a photosensitizer and nucleic acid carriers en-subtitle= kn-subtitle= en-abstract= kn-abstract=mRNA has great potential for therapeutic applications because it can encode a variety of proteins and antigens, in addition to advantages over DNA in terms of gene expression without genomic integration, nuclear localization, or transcription. However, therapeutic applications of mRNA require safe and effective delivery into target cells. Therefore, we aimed to investigate photochemical internalization (PCI) as a promising strategy for delivering mRNA to target cells. In this strategy, mRNA is taken up into cells by endocytosis, accumulates in endosomes, and is released in a light-dependent manner from the endosomes using an endosome-accumulating photosensitizer, aluminum phthalocyanine disulfonate (AlPcS2a), in combination with nucleic acid carrier molecules. We compared the efficacy of various nucleic acid carriers, including branched polyethyleneimine (bPEI) and poly{N'-[N-(2-aminoethyl)-2-aminoethyl] aspartamide} (PAsp(DET)) under the same conditions for PCI-based mRNA delivery. Our results indicated that bPEI and PAsp(DET) at low N/P ratios exhibited efficient light-enhancement of mRNA expression by PCI with AlPcS2a. Notably, bPEI exhibited the highest light-dependent mRNA delivery among the carriers evaluated (including cationic polymers, cationic peptides, and lipids), whereas PAsp(DET) showed promise for clinical use because of its lower toxicity compared with bPEI. This PCI strategy allows effective cytosolic mRNA delivery at low N/P ratios, thereby reducing cationic carrier molecule-induced cytotoxicity. This method allows spatiotemporal control of protein expression and holds potential for novel light-dependent mRNA therapies. Overall, this study provided valuable insights into optimizing mRNA delivery systems for therapeutic applications. en-copyright= kn-copyright= en-aut-name=MaemotoHayaki en-aut-sei=Maemoto en-aut-mei=Hayaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzakiRyohei en-aut-sei=Suzaki en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeKazunori en-aut-sei=Watanabe en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItakaKeiji en-aut-sei=Itaka en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University kn-affil= affil-num=5 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=mRNA kn-keyword=mRNA en-keyword=Photochemical internalization kn-keyword=Photochemical internalization en-keyword=Photosensitizer kn-keyword=Photosensitizer END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue=1 article-no= start-page=32 end-page=35 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250627 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The relationship between sleep disorder and dairy intake in university students of the nursing department in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study was conducted to clarify the relationship between sleep disorders and frequency, or timing of dairy intake with 192 university students in Japan. Pearson’s chi-squared test was carried out to find the relationship between two groups of sleep disorders and the timing of dairy product intake (p = 0.034, df = 4, χ2 = 10.38). The sleep disorder occurred significantly less if participants took a dairy product in the morning (p = 0.004) and significantly more when participants took a dairy product in the afternoon (p = 0.028). The findings showed that consuming dairy products in the morning is effective in treating sleep disorders. en-copyright= kn-copyright= en-aut-name=EdahiroShiho en-aut-sei=Edahiro en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakebayashiMaho en-aut-sei=Takebayashi en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiYui en-aut-sei=Kobayashi en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahataYoko en-aut-sei=Takahata en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Nursing, Faculty of Medicine, Okayama University kn-affil= affil-num=2 en-affil=Department of Nursing, Faculty of Medicine, Okayama University kn-affil= affil-num=3 en-affil=Department of Nursing, Faculty of Medicine, Okayama University kn-affil= affil-num=4 en-affil=Department of Nursing, Faculty of Medicine, Okayama University kn-affil= en-keyword=sleep disorder kn-keyword=sleep disorder en-keyword=the frequency of dairy products kn-keyword=the frequency of dairy products en-keyword=the timing of dairy products kn-keyword=the timing of dairy products en-keyword=nursing students kn-keyword=nursing students END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=311 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Co-occurrence of interstitial lung disease and pulmonary embolism as adverse events of adjuvant osimertinib treatment for EGFR mutant non-small cell lung cancer: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Postoperative osimertinib for EGFR mutant non-small cell lung cancer has become the standard of care. However, its adverse events in clinical practice remain unclear. We report a case of interstitial lung disease and pulmonary embolism occurring simultaneously as adverse events during adjuvant osimertinib treatment.
Case presentation A 74-year-old woman, diagnosed with left lower lobe lung adenocarcinoma harboring an EGFR mutation, underwent a left lower lobectomy with lymph node dissection. During adjuvant osimertinib therapy, the patient developed respiratory distress with hypoxia, leading to the diagnosis of interstitial lung disease. Despite immediate steroid therapy, respiratory distress persisted, the patient developed leg edema. She was diagnosed with deep vein thrombosis and pulmonary embolism via contrast-enhanced computed tomography scan. Following treatment with steroid and anticoagulation, her clinical symptoms improved rapidly, and she showed no recurrence of interstitial lung disease, pulmonary embolism, or lung cancer over the following nine months.
Conclusions We encountered a case of interstitial lung disease and pulmonary embolism occurring simultaneously as adverse events during adjuvant osimertinib treatment. In patients with osimertinib-induced interstitial lung disease, particularly when respiratory symptoms show poor improvement with steroid treatment, the possibility of pulmonary embolism complications should be suspected. en-copyright= kn-copyright= en-aut-name=ManabeKenta en-aut-sei=Manabe en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FurukawaShinichi en-aut-sei=Furukawa en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SenoTomoya en-aut-sei=Seno en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshimuraKousei en-aut-sei=Ishimura en-aut-mei=Kousei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=Osimertinib kn-keyword=Osimertinib en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Interstitial lung disease kn-keyword=Interstitial lung disease en-keyword=Pulmonary embolism kn-keyword=Pulmonary embolism 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=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=One-pot synthesis of trans-2,3-diaminoindolines through 2,3-diamination of electrophilic indolines en-subtitle= kn-subtitle= en-abstract= kn-abstract=Despite recent advances in the synthesis of 2,3-diaminoindole derivatives, construction of 2,3-diaminoindolines, whose two amine moieties on each molecule differ from one another has yet to be achieved. In this work, we developed a concise one-pot protocol for differentiated diamination involving reacting a C2,C3-electrophilic indole reagent with amines to access a variety of previously inaccessible 2,3-diaminoindolines. Furthermore, the synthetic utility of this protocol was demonstrated by a successful gram-scale reaction and further transformation of the 2,3-diaminoindolines. en-copyright= kn-copyright= en-aut-name=KoboriYuito en-aut-sei=Kobori en-aut-mei=Yuito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TokushigeKeisuke en-aut-sei=Tokushige en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AbeTakumi en-aut-sei=Abe en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=7 article-no= start-page=808 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Carnosol, a Rosemary Ingredient Discovered in a Screen for Inhibitors of SARM1-NAD+ Cleavage Activity, Ameliorates Symptoms of Peripheral Neuropathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sterile alpha and Toll/interleukin receptor motif-containing protein 1 (SARM1) is a nicotinamide adenine dinucleotide (NAD+) hydrolase involved in axonal degeneration and neuronal cell death. SARM1 plays a pivotal role in triggering the neurodegenerative processes that underlie peripheral neuropathies, traumatic brain injury, and neurodegenerative diseases. Importantly, SARM1 knockdown or knockout prevents the degeneration; as a result, SARM1 has been attracting attention as a potent therapeutic target. In recent years, the development of several SARM1 inhibitors derived from synthetic chemical compounds has been reported; however, no dietary ingredients with SARM1 inhibitory activity have been identified. Therefore, we here focused on dietary ingredients and found that carnosol, an antioxidant contained in rosemary, inhibits the NAD+-cleavage activity of SARM1. Purified carnosol inhibited the enzymatic activity of SARM1 and suppressed neurite degeneration and cell death induced by the anti-cancer medicine vincristine (VCR). Carnosol also inhibited VCR-induced hyperalgesia symptoms, suppressed the loss of intra-epidermal nerve fibers in vivo, and reduced the blood fluid level of phosphorylated neurofilament-H caused by an axonal degeneration event. These results indicate that carnosol has a neuroprotective effect via SARM1 inhibition in addition to its previously known antioxidant effect via NF-E2-related factor 2 and thus suppresses neurotoxin-induced peripheral neuropathy. en-copyright= kn-copyright= en-aut-name=MurataHitoshi en-aut-sei=Murata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgawaKazuki en-aut-sei=Ogawa en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuiYu en-aut-sei=Yasui en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OchiToshiki en-aut-sei=Ochi en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoKen-Ichi en-aut-sei=Yamamoto en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WadaYoji en-aut-sei=Wada en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraHiromichi en-aut-sei=Nakamura en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Tama Biochemical Co., Ltd. kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Tama Biochemical Co., Ltd. kn-affil= affil-num=9 en-affil=Tama Biochemical Co., Ltd. kn-affil= affil-num=10 en-affil=Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=SARM1 kn-keyword=SARM1 en-keyword=carnosol kn-keyword=carnosol en-keyword=NAD+ kn-keyword=NAD+ en-keyword=axon degeneration kn-keyword=axon degeneration en-keyword=peripheral neuropathy kn-keyword=peripheral neuropathy END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e202510319 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250626 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of a Vinylated Cyclic Allene: A Fleeting Strained Diene for the Diels?Alder Reaction en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fleeting molecules possessing strained multiple bonds are important components in organic synthesis due to their ability to undergo various chemical reactions driven by the release of strain energy. Although the use of strained π-bonds as 2π components, represented by dienophiles in Diels?Alder reactions, has been well studied, “the strained diene (4π component) approach” for molecular construction remains underexplored. Herein, we report the design of a vinyl cyclic allene (1-vinyl-1,2-cyclohexadiene) as a highly reactive strained diene and the development of its Diels?Alder reactions. Experimental and computational studies of vinyl cyclic allenes revealed that this diene system undergoes cycloaddition with dienophiles regio- and stereoselectively under mild reaction conditions. These studies also provide insight into the reactivity and selectivity of the system. The strained diene approach enables the convergent construction of polycyclic molecules through bond disconnections distinct from conventional retrosynthetic analysis, thus offering an efficient strategy for the assembly of functional molecules. en-copyright= kn-copyright= en-aut-name=MizoguchiHaruki en-aut-sei=Mizoguchi en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ObataTakumi en-aut-sei=Obata en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiraiTaiki en-aut-sei=Hirai en-aut-mei=Taiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KomatsuManaka en-aut-sei=Komatsu en-aut-mei=Manaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakakuraAkira en-aut-sei=Sakakura en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Activation strain model kn-keyword=Activation strain model en-keyword=Carbocycles kn-keyword=Carbocycles en-keyword=Diels?Alder reaction kn-keyword=Diels?Alder reaction en-keyword=Strained diene kn-keyword=Strained diene en-keyword=Vinylated cyclic allene kn-keyword=Vinylated cyclic allene 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=2025 dt-pub=20250604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy of transcatheter patent foramen ovale closure for drug-resistant migraine: initial experience in Japan and long-term outcome en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study evaluates the efficacy and safety of transcatheter patent foramen ovale (PFO) closure for the treatment of drug-resistant migraine in Japan. Previous studies have suggested a potential benefit for migraine with aura, although large-scale trials in the United States and Europe have failed to confirm efficacy as a primary endpoint. The study included 27 patients (mean age 36.4 years, 15 female, 21 with aura) who had more than two migraine attacks per month despite medication. All had PFO confirmed by transesophageal echocardiography and underwent transcatheter closure with the Amplatzer PFO Occluder. Patients were followed up to 12 months with migraine severity monitored by headache specialist. The procedure was successful and without complications in all cases. One patient required a larger occluder (35 mm) due to the size of PFO. At 12 months, 22 of 27 (81%) patients reported either complete resolution or improvement of migraine. Specifically, 10 of 21 (48%) patients with aura experienced complete resolution of migraine at one year. Patients without aura had a lower response rate, with only one case of complete resolution. Despite limitations such as the lack of a control group and potential patient selection bias, the study demonstrated that PFO closure may provide significant relief for patients with drug-resistant migraine, particularly those with aura. These findings support further investigation to better define its clinical indications and potential benefits. en-copyright= kn-copyright= en-aut-name=AkagiTeiji en-aut-sei=Akagi en-aut-mei=Teiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakayaYoichi en-aut-sei=Takaya en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MikiTakashi en-aut-sei=Miki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakayamaRie en-aut-sei=Nakayama en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakashimaMitsuki en-aut-sei=Nakashima en-aut-mei=Mitsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiYoshiaki en-aut-sei=Takahashi en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HishikawaNozomi en-aut-sei=Hishikawa en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Patent foramen ovale kn-keyword=Patent foramen ovale en-keyword=Migraine kn-keyword=Migraine en-keyword=Headache kn-keyword=Headache en-keyword=Stroke kn-keyword=Stroke en-keyword=Catheter kn-keyword=Catheter END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=4 article-no= start-page=773 end-page=782 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Japanese translation of the Functional Assessment of Cancer Therapy-Breast?+?4 (FACT-B?+?4) following international guidelines: a verification of linguistic validity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background For breast cancer patients, postoperative lymphedema and upper limb movement disorders are serious complications that absolutely reduce their quality of life (QOL). To evaluate this serious complication, we used “Quick Dash” or “FACT-B”, which can assess a patient's physical, social, emotional, and functional health status. To evaluate their breast cancer surgery-related dysfunction correctly, “FACT-B?+?4” was created by adding four questions about “arm swelling'' and “tenderness”. We have translated it into Japanese according to international translation guidelines.
Methods At the beginning, we contacted FACT headquarters that we would like to create a Japanese version of FACT-B?+?4. They formed the FACIT Trans Team (FACIT) following international translation procedures, and then, we began translating according to them. The steps are 1: perform “Forward and Reverse translations” to create a “Preliminary Japanese version”, 2: request the cooperation of 5 breast cancer patients and “conduct a pilot study” and “questionnaire survey”, and 3: amendments and final approval based on pilot study results and clinical perspectives.
Result In Step1, FACIT requested faithful translation of the words, verbs, and nouns from the original text. In Step2, patients reported that they felt uncomfortable with the Japanese version words such as “numb'' and “stiffness'' and felt that it might be difficult to describe their symptoms accurately. In Step3, we readjusted the translation to be more concise and closer to common Japanese language, and performed “Step1” again to ensure that the translation definitely retained the meaning of the original.
Conclusion A Japanese version of FACT has existed until now, but there was no Japanese version of FACT-B?+?4, which adds four additional items to evaluate swelling and pain in the upper limbs. This time, we have created a Japanese version that has been approved by FACT. en-copyright= kn-copyright= en-aut-name=TsukiokiTakahiro en-aut-sei=Tsukioki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakataNozomu en-aut-sei=Takata en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DennisSaya R. en-aut-sei=Dennis en-aut-mei=Saya R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 ORCID= en-aut-name=TakayamaShin en-aut-sei=Takayama en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KitagawaDai en-aut-sei=Kitagawa en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KikawaYuichiro en-aut-sei=Kikawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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=12 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=13 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=14 ORCID= affil-num=1 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Simpson Querrey Biomedical Research Center, Northwestern University kn-affil= affil-num=3 en-affil=Department of Preventive Medicine Feinberg School of Medicine, Northwestern University kn-affil= affil-num=4 en-affil=Department of Breast and Endocrine Surgery, Akita University Hospital kn-affil= affil-num=5 en-affil=Department of Breast Surgical Oncology, Social Medical Corporation Hakuaikai Sagara Hospital kn-affil= affil-num=6 en-affil=Department of Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital of JFCR kn-affil= affil-num=7 en-affil=Department of Breast Surgery, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Breast Surgical Oncology, National Center for Global Health and Medicine kn-affil= affil-num=9 en-affil=Department of Breast Surgery, Kansai Medical 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 Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=13 en-affil=Department of Breast Cancer, Gunma Prefectural Cancer Center kn-affil= affil-num=14 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=FACT-B kn-keyword=FACT-B en-keyword=FACT-B+4 kn-keyword=FACT-B+4 en-keyword=QOL kn-keyword=QOL END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=4 article-no= start-page=510 end-page=524 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250626 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=C1orf50 Drives Malignant Melanoma Progression Through the Regulation of Stemness en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Recent advancements in omics analysis have significantly enhanced our understanding of the molecular pathology of malignant melanoma, leading to the development of novel therapeutic strategies that target specific vulnerabilities within the disease. Despite these improvements, the factors contributing to the poor prognosis of patients with malignant melanoma remain incompletely understood. The aim of this study was to investigate the role of C1orf50 (Chromosome 1 open reading frame 50), a gene previously of unknown function, as a prognostic biomarker in melanoma.
Materials and Methods: We performed comprehensive transcriptome data analysis and subsequent functional validation of the human Skin Cutaneous Melanoma project from The Cancer Genome Atlas (TCGA).
Results: Elevated expression levels of C1orf50 correlated with worse survival outcomes. Mechanistically, we revealed that C1orf50 plays a significant role in the regulation of cell cycle processes and cancer cell stemness, providing a potential avenue for novel therapeutic interventions in melanoma.
Conclusion: This study is the first to identify C1orf50 as a prognostic biomarker in melanoma. The clinical relevance of our results sheds light on the importance of further investigation into the biological mechanisms underpinning C1orf50’s impact on melanoma progression and patient prognosis. en-copyright= kn-copyright= en-aut-name=OTANIYUSUKE en-aut-sei=OTANI en-aut-mei=YUSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MAEKAWAMASAKI en-aut-sei=MAEKAWA en-aut-mei=MASAKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TANAKAATSUSHI en-aut-sei=TANAKA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PE?ATIRSO en-aut-sei=PE?A en-aut-mei=TIRSO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CHINVANESSA D. en-aut-sei=CHIN en-aut-mei=VANESSA D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ROGACHEVSKAYAANNA en-aut-sei=ROGACHEVSKAYA en-aut-mei=ANNA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=ROEHRLMICHAEL H. en-aut-sei=ROEHRL en-aut-mei=MICHAEL H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FUJIMURAATSUSHI en-aut-sei=FUJIMURA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=2 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=3 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=4 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=5 en-affil=UMass Chan Medical School, UMass Memorial Medical Center kn-affil= affil-num=6 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=9 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=C1orf50 kn-keyword=C1orf50 en-keyword=melanoma kn-keyword=melanoma en-keyword=cancer stem cells kn-keyword=cancer stem cells en-keyword=YAP/TAZ kn-keyword=YAP/TAZ 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=2025 dt-pub=20250624 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dual functions of SNAP25 in mouse taste buds en-subtitle= kn-subtitle= en-abstract= kn-abstract=Type III cells in mouse taste buds are considered to transmit aversive stimuli, such as sourness, to the gustatory nerve through vesicular synapses. Synaptosome-associated protein 25 (SNAP25) might contribute to synaptic vesicular release in sour sensation, although direct evidence has been lacking. Here, we demonstrated that epithelia-specific Snap25 conditional knockout (cKO) mice exhibited a significant reduction in the number of type III cells. Notably, the proportion of 5-ethynyl 2′-deoxyuridine-positive post-mitotic type III cells in Snap25 cKO mice was significantly lower on tracing day 14, but not at day 7, which suggests that SNAP25 contributes to the maintenance of type III cells. In a short-term lick test, Snap25 cKO (sour taste absent) and Snap25/ transient receptor potential vanilloid 1 double KO (sour taste and somatosensory absent) mice exhibit a significantly higher lick response to sour tastants, confirming the role of SNAP25 for sour sensation. Electrophysiological recordings of the chorda tympani nerve reveal nearly abolished ammonium and sour taste responses in Snap25 cKO mice, which concludes sour-dependent synapse transmission in type III cells. Overall, these data suggest that vesicular synapses in taste buds are indispensable for transmission of information from, and the replenishment of, sour-sensitive type III taste cells. en-copyright= kn-copyright= en-aut-name=HorieKengo en-aut-sei=Horie en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangKuanyu en-aut-sei=Wang en-aut-mei=Kuanyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuangHai en-aut-sei=Huang en-aut-mei=Hai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasumatsuKeiko en-aut-sei=Yasumatsu en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NinomiyaYuzo en-aut-sei=Ninomiya en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitohYoshihiro en-aut-sei=Mitoh en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Tokyo Dental Junior College kn-affil= affil-num=5 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=sour taste kn-keyword=sour taste en-keyword=synapse kn-keyword=synapse en-keyword=taste buds kn-keyword=taste buds en-keyword=taste nerve kn-keyword=taste nerve en-keyword=Type III cells kn-keyword=Type III cells END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=85 end-page=104 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220812 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CyNER: Information Extraction from?Unstructured Text of?CTI Sources with?Noncontextual IOCs en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cybersecurity threats have been increasing and growing more sophisticated year by year. In such circumstances, gathering Cyber Threat Intelligence (CTI) and following up with up-to-date threat information is crucial. Structured CTI such as Structured Threat Information eXpression (STIX) is particularly useful because it can automate security operations such as updating FW/IDS rules and analyzing attack trends. However, as most CTIs are written in natural language, manual analysis with domain knowledge is required, which becomes quite time-consuming.
In this work, we propose CyNER, a method for automatically structuring CTIs and converting them into STIX format. CyNER extracts named entities in the context of CTI and then extracts the relations between named entities and IOCs in order to convert them into STIX. In addition, by using key phrase extraction, CyNER can extract relations between IOCs that lack contextual information, such as those listed at the bottom of a CTI, and named entities. We describe our design and implementation of CyNER and demonstrate that it can extract named entities with the F-measure of 0.80 and extract relations between named entities and IOCs with the maximum accuracy of 81.6%. Our analysis of structured CTI showed that CyNER can extract IOCs that are not included in existing reputation sites, and that it can automatically extract IOCs that have been exploited for a long time and across multiple attack groups. CyNER is thus expected to contribute to the efficiency of CTI analysis. en-copyright= kn-copyright= en-aut-name=FujiiShota en-aut-sei=Fujii en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaguchiNobutaka en-aut-sei=Kawaguchi en-aut-mei=Nobutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShigemotoTomohiro en-aut-sei=Shigemoto en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamauchiToshihiro en-aut-sei=Yamauchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research & Development Group, Hitachi, Ltd. kn-affil= affil-num=3 en-affil=Research & Development Group, Hitachi, Ltd. kn-affil= affil-num=4 en-affil=Faculty of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=292 end-page=297 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Analyzing Post-injection Attacker Activities in IoT Devices: A Comprehensive Log Analysis Approach en-subtitle= kn-subtitle= en-abstract= kn-abstract=With the continuous proliferation of Internet of Things (IoT) devices, malware threats that specifically target these devices continue to increase. The urgent need for robust security measures is predicated on a comprehensive understanding of the behavioral patterns of IoT malware. However, previous studies have often overlooked the analysis of command sequences in Telnet logs. This study bridges this research gap by examining the post-injection behaviors of attackers. By analyzing a vast dataset comprising more than ten million logs collected from an IoT honeypot, we reveal three distinct post-injection activity patterns, each with unique characteristics. These patterns provide pivotal insights that not only help distinguish between legitimate operations and attempted attacks, but also drive the development of robust cybersecurity measures that effectively deter such behaviors. The nuances discovered in this study contribute significantly to IoT security by enhancing our understanding of malware tactics and informing targeted defense strategies. en-copyright= kn-copyright= en-aut-name=VictorHervet en-aut-sei=Victor en-aut-mei=Hervet kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiSatoru en-aut-sei=Kobayashi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamauchiToshihiro en-aut-sei=Yamauchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Malware analysis kn-keyword=Malware analysis en-keyword=IoT kn-keyword=IoT en-keyword=Honeypot kn-keyword=Honeypot en-keyword=Log analysis kn-keyword=Log analysis en-keyword=Attack patterns kn-keyword=Attack patterns END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=6 article-no= start-page=e86695 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250624 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Managing Persistent Pupillary Membranes With Surgery or Medication: A Report of Three Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=The persistent pupillary membrane, as a congenital anomaly, is a remnant of a network of feeding blood vessels for the lens of the eye, called tunica vasculosa lentis. This study reports three patients with persistent pupillary membrane in both eyes who presented in different situations and were managed differently to achieve better vision. The first child (Case 1) who had been seen initially at the age of two years complained of severe photophobia even though he had good visual acuity, and hence, he and his family chose surgical resection of the pupillary membrane in both eyes at the age of six years just before the admission to an elementary school. He did not develop any surgical complications, such as cataract and glaucoma, and maintained the visual acuity in decimals of 1.2 in both eyes at the age of 17 years.
The second child (Case 2), who was seen first at the age of one month, had persistent pupillary membranes in both eyes, together with Peters' anomaly in the left eye. The iris process adhesion to the corneal inner surface was visualized later by optical coherence tomography. She wore full-correction glasses and obtained the visual acuity of 0.7 in the right eye, so she had no problem studying at an elementary school. She used topical 1% atropine once a week in both eyes to maintain pupillary dilation and also used 0.5% timolol and 1% brinzolamide as pressure-lowering eye drops in the left eye with Peters' anomaly.
The third patient (Case 3) with persistent pupillary membranes in both eyes complained of vision problems for the first time at the age of 49 years when she developed cataract. Surgical resection of the pupillary membrane was done in the initial phase of cataract surgery with intraocular lens implantation in both eyes. At surgical resection of the pupillary membrane, a safe and efficient way was to cut the root of the pupillary membrane on the iris surface with scissors, and then the isolated tissues of the pupillary membrane were pulled out with forceps from the side port at the corneal limbus. Pathological examinations of the excised tissues showed blood vessels with red blood cells in the lumen. In such a rare congenital disease as the persistent pupillary membrane, a case-based approach to choose a better option in different conditions from individual to individual is still required to have a better vision in learning at school and in daily working life. 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=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Division of Healthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=anterior segment dysgenesis kn-keyword=anterior segment dysgenesis en-keyword=cataract kn-keyword=cataract en-keyword=forceps kn-keyword=forceps en-keyword=optical coherence tomography kn-keyword=optical coherence tomography en-keyword=persistent pupillary membrane kn-keyword=persistent pupillary membrane en-keyword=peters anomaly kn-keyword=peters anomaly en-keyword=resection kn-keyword=resection en-keyword=scissors kn-keyword=scissors en-keyword=vitrectomy cutter kn-keyword=vitrectomy cutter END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=6 article-no= start-page=e85680 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Whole-Eye Radiation for the Local Control of Choroidal Lymphoma in Primary Central Nervous System Lymphoma: A 14-Year Case Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Involved-site radiation therapy is effective for curative and palliative treatments of cancers, including lymphoma. This case study describes the use of whole-eye radiation for primary intraocular lymphoma occurring during primary central nervous system lymphoma. The patient, a 68-year-old man, developed personality changes and apathy two weeks after cataract surgery combined with vitrectomy for vitreous opacity in the left eye. Magnetic resonance imaging revealed a mass lesion in the left frontal lobe, and biopsy by craniotomy confirmed diffuse large B-cell lymphoma. He underwent chemotherapy using rituximab combined with high-dose methotrexate and high-dose cytarabine in association with intrathecal methotrexate and cytarabine injections, leading to complete remission. At age 75, he noticed forgetfulness, and fluorodeoxyglucose positron emission tomography and magnetic resonance imaging revealed a relapse of lymphoma in the splenium of the corpus callosum. He underwent chemotherapy using rituximab combined with high-dose methotrexate, followed by monthly rituximab monotherapy for one year and then rituximab monotherapy every two months for one year. He maintained complete remission with no treatment until age 78, when he developed subretinal choroidal lesions in the left eye and underwent whole-eye radiation at 40 Gy. One year later, he developed subretinal choroidal lesions in the right eye and underwent whole-eye radiation at 40 Gy. At age 81, he had lower limb weakness with disorientation. Magnetic resonance imaging showed a relapse of lymphoma in the right frontal to temporal lobe. The brain lesions showed a marked response to four weeks of oral tirabrutinib as a salvage therapy, but the lesions regrew, and the patient died seven months later. Throughout the treatment, he maintained a visual acuity of 0.7 (decimal scale) in both eyes. In conclusion, whole-eye radiation should be considered as a treatment option for the local control of active intraocular lymphoma, especially choroidal lesions, for patients with primary central nervous system lymphoma with no active brain lesions and without systemic treatment. 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=YanoTomofumi en-aut-sei=Yano en-aut-mei=Tomofumi 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=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=NishimuraHirotake en-aut-sei=Nishimura en-aut-mei=Hirotake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=Department of Internal Medicine, Okayama Rosai Hospital 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=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=brain biopsy kn-keyword=brain biopsy en-keyword=bruton tyrosine kinase (btk) inhibitor kn-keyword=bruton tyrosine kinase (btk) inhibitor en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=diffuse large b-cell lymphoma kn-keyword=diffuse large b-cell lymphoma en-keyword=fluorodeoxyglucose positron emission tomography kn-keyword=fluorodeoxyglucose positron emission tomography en-keyword=primary central nervous system lymphoma kn-keyword=primary central nervous system lymphoma en-keyword=primary intraocular (vitreoretinal) lymphoma kn-keyword=primary intraocular (vitreoretinal) lymphoma en-keyword=radiation therapy (radiotherapy) kn-keyword=radiation therapy (radiotherapy) en-keyword=tirabrutinib kn-keyword=tirabrutinib en-keyword=whole-eye radiation kn-keyword=whole-eye radiation END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=5 article-no= start-page=e83484 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Detailed Ophthalmic and Pathological Features of Choroidal Metastasis From Breast Cancer: A Case Series of Five Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Breast cancer causes choroidal metastases on rare occasions. This study presented the eye manifestations of choroidal metastases from breast cancer and their response to treatments in detail as well as their pathological correlation in five patients. The patients' age at the diagnosis of breast cancer ranged from 24 to 69 years (median: 37 years). The time from the diagnosis of breast cancer to the detection of metastases was concurrent in one patient, two years later in three patients, and six years later in the other patient. The time from the detection of systemic metastases to the detection of choroidal metastases was the same in one patient, while it ranged from one to seven years later in four patients. Choroidal metastases were in the unilateral eye of four patients, whereas they were in both eyes of one patient. Choroidal metastases manifested as one or a few nodular or flat choroidal lesions with serous retinal detachment. As for the treatment of choroidal metastases, enucleation of the right eye was chosen based on the patient's wish as well as the family's wish in the earliest patient when cancer notification was not the norm in Japan. In the other four patients, whole-eye radiation was performed to reduce the choroidal metastatic lesions. As regards the prognosis, which was available in four patients, three patients died within one year from the diagnosis of choroidal metastases, while one patient died one year and eight months later. Regarding the pathology of breast cancer, which was available in four patients, immunostaining of the preserved enucleated eye in the earliest patient revealed that breast cancer cells in the choroidal metastatic lesion were positive for estrogen receptor and negative for progesterone receptor and human epidermal growth factor receptor 2 (HER2). Invasive ductal carcinoma in two patients was positive for estrogen receptor and negative for HER2, while invasive ductal carcinoma in the other patient was triple-negative for estrogen receptor, progesterone receptor, and HER2 with a high Ki-67 index. In conclusion, the prognosis for life was poor in patients with breast cancer who developed choroidal metastases. Choroidal metastatic lesions showed a response to whole-eye radiation to improve the quality of vision at the end of life. Vision-related symptoms should be monitored in the course of chemotherapy for systemic metastases. 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=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=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MuraokaAtsushi en-aut-sei=Muraoka en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= affil-num=1 en-affil=Division of Healthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Surgery, Kagawa Rosai Hospital kn-affil= affil-num=5 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=choroidal metastasis kn-keyword=choroidal metastasis en-keyword=estrogen receptor kn-keyword=estrogen receptor en-keyword=her2 kn-keyword=her2 en-keyword=immunostaining kn-keyword=immunostaining en-keyword=invasive ductal carcinoma kn-keyword=invasive ductal carcinoma en-keyword=ki-67 kn-keyword=ki-67 en-keyword=progesterone receptor kn-keyword=progesterone receptor en-keyword=radiation kn-keyword=radiation END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=21 article-no= start-page=13372 end-page=13380 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250520 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Unraveling the Molecular Mechanism of Transient Multilamellar Formation in Ethanol-Modified Vesicle Solutions en-subtitle= kn-subtitle= en-abstract= kn-abstract=A recent microfluidic-based small-angle X-ray scattering (SAXS) measurement intriguingly suggested the transient formation of multilamellar structures during the mixing of unilamellar vesicles with ethanol in an aqueous solution. This study explores a possible molecular mechanism underlying this phenomenon, primarily through coarse-grained molecular dynamics (CG-MD) simulations. We first examined lipid aggregate morphology as a function of ethanol concentration in an aqueous solution. Even though vesicles were observed in pure aqueous solution, increasing ethanol concentrations led to more frequent pore formation in vesicular membranes. At ethanol concentrations above 52%, vesicles destabilized and transformed into worm-like micelles. We hypothesized that the transient multilamellar structures might arise from vesicle stacking due to variations in the effective interactions between vesicles. However, a series of potential of mean force (PMF) calculations consistently showed repulsive interactions between vesicles, regardless of ethanol concentration, ruling out this possibility. In contrast, once lipid aggregates transformed into worm-like micelles, the PMF barrier between them dropped (?5kBT), promoting fusion. Our CG-MD simulations further demonstrated that lipid aggregates (micelles) readily fused and grew in high ethanol concentrations. Upon subsequent exposure to lower ethanol levels, these enlarged aggregates reorganized into vesicles with internal lamellar structure─multilamellar vesicles. These findings suggest that the heterogeneous mixing of unilamellar vesicular solutions with ethanol in a microfluidic device plays a key role in the emergence of transient multilamellar structures. en-copyright= kn-copyright= en-aut-name=ShibataKana en-aut-sei=Shibata en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaekiMasatoshi en-aut-sei=Maeki en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokeshiManabu en-aut-sei=Tokeshi en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShinodaWataru en-aut-sei=Shinoda en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Materials Chemistry, Nagoya University kn-affil= affil-num=2 en-affil=Division of Applied Chemistry, Faculty of Engineering, Hokkaido University kn-affil= affil-num=3 en-affil=Division of Applied Chemistry, Faculty of Engineering, Hokkaido University kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=6 article-no= start-page=e70126 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sulphur‐Acquisition Pathways for Cysteine Synthesis Confer a Fitness Advantage to Bacteria in Plant Extracts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bacteria and plants are closely associated with human society, in fields such as agriculture, public health, the food industry, and waste disposal. Bacteria have evolved nutrient-utilisation systems adapted to achieve the most efficient growth in their major habitats. However, empirical evidence to support the significance of bacterial nutrient utilisation in adaptation to plants is limited. Therefore, we investigated the genetic and nutritional factors required for bacterial growth in plant extracts by screening an Escherichia coli gene-knockout library in vegetable-based medium. Mutants lacking genes involved in sulphur assimilation, whereby sulphur is transferred from sulphate to cysteine, exhibited negligible growth in vegetable-based medium or plant extracts, owing to the low cysteine levels. The reverse transsulphuration pathway from methionine, another pathway for donating sulphur to cysteine, occurring in bacteria such as Bacillus subtilis, also played an important role in growth in plant extracts. These two sulphur-assimilation pathways were more frequently observed in plant-associated than in animal-associated bacteria. Sulphur-acquisition pathways for cysteine synthesis thus play a key role in bacterial growth in plant-derived environments such as plant residues and plant exudates. 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=YamaguchiSaki en-aut-sei=Yamaguchi en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsukaokaTaketo en-aut-sei=Tsukaoka en-aut-mei=Taketo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsunodaMakoto en-aut-sei=Tsunoda en-aut-mei=Makoto 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 Pharmaceutical Sciences, The University of Tokyo 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=Bacillus subtilis kn-keyword=Bacillus subtilis en-keyword=bacterial nutrient utilisation kn-keyword=bacterial nutrient utilisation en-keyword=cysteine synthesis kn-keyword=cysteine synthesis en-keyword=Escherichia coli kn-keyword=Escherichia coli en-keyword=plant-derived environments kn-keyword=plant-derived environments en-keyword=sulphur acquisition pathway kn-keyword=sulphur acquisition pathway 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=2025 dt-pub=20250620 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=International Consensus Histopathological Criteria for Subtyping Idiopathic Multicentric Castleman Disease Based on Machine Learning Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder classified into three recognized clinical subtypes?idiopathic plasmacytic lymphadenopathy (IPL), TAFRO, and NOS. Although clinical criteria are available for subtyping, diagnostically challenging cases with overlapping histopathological features highlight the need for an improved classification system integrating clinical and histopathological findings. We aimed to develop an objective histopathological subtyping system for iMCD that closely correlates with the clinical subtypes. Excisional lymph node specimens from 94 Japanese iMCD patients (54 IPL, 28 TAFRO, 12 NOS) were analyzed for five key histopathological parameters: germinal center (GC) status, plasmacytosis, vascularity, hemosiderin deposition, and “whirlpool” vessel formation in GC. Using hierarchical clustering, we visualized subgroups and developed a machine learning-based decision tree to differentiate the clinical subtypes and validated it in an external cohort of 12 patients with iMCD. Hierarchical cluster analysis separated the IPL and TAFRO cases into mutually exclusive clusters, whereas the NOS cases were interspersed between them. Decision tree modeling identified plasmacytosis, vascularity, and whirlpool vessel formation as key features distinguishing IPL from TAFRO, achieving 91% and 92% accuracy in the training and test sets, respectively. External validation correctly classified all IPL and TAFRO cases, confirming the reproducibility of the system. Our histopathological classification system closely aligns with the clinical subtypes, offering a more precise approach to iMCD subtyping. It may enhance diagnostic accuracy, guide clinical decision-making for predicting treatment response in challenging cases, and improve patient selection for future research. Further validation of its versatility and clinical utility is required. en-copyright= kn-copyright= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaratakeTomoka en-aut-sei=Haratake en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SumiyoshiRemi en-aut-sei=Sumiyoshi en-aut-mei=Remi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UjiieHideki en-aut-sei=Ujiie en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawaharaYuri en-aut-sei=Kawahara en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KogaTomohiro en-aut-sei=Koga en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UekiMasao en-aut-sei=Ueki en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LaczkoDorottya en-aut-sei=Laczko en-aut-mei=Dorottya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OksenhendlerEric en-aut-sei=Oksenhendler en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FajgenbaumDavid C. en-aut-sei=Fajgenbaum en-aut-mei=David C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=van RheeFrits en-aut-sei=van Rhee en-aut-mei=Frits kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawakamiAtsushi en-aut-sei=Kawakami en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease, TAFRO and Related Ddisease Research Group kn-affil= affil-num=6 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=7 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease, TAFRO and Related Ddisease Research Group kn-affil= affil-num=9 en-affil=School of Information and Data Sciences, Nagasaki University kn-affil= affil-num=10 en-affil=Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania kn-affil= affil-num=11 en-affil=Department of Clinical Immunology, H?pital Saint-Louis kn-affil= affil-num=12 en-affil=Center for Cytokine Storm Treatment and Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=13 en-affil=Myeloma Center, University of Arkansas for Medical Sciences kn-affil= affil-num=14 en-affil=The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease, TAFRO and Related Ddisease Research Group kn-affil= affil-num=15 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=clinical subtype kn-keyword=clinical subtype en-keyword=histopathological criteria kn-keyword=histopathological criteria en-keyword=idiopathic multicentric castleman disease kn-keyword=idiopathic multicentric castleman disease en-keyword=lymphoproliferative disease kn-keyword=lymphoproliferative disease en-keyword=machine-learning kn-keyword=machine-learning 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=2025 dt-pub=20250623 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Transformation of α,β-Unsaturated Aldehydes with a Small Amount of Electricity: Cyanosilylation, Isomerization, and Nucleophilic Addition en-subtitle= kn-subtitle= en-abstract= kn-abstract=An electrochemical method was developed to convert α,β-unsaturated aldehydes into carboxylic acid derivatives via cyanosilylation, isomerization, and nucleophilic addition. This reaction is more sustainable than the usual electrochemical organic reaction because this reaction proceeds catalytically with active species generated by a very small amount of electricity. Furthermore, scale-up synthesis with a flow reactor has been achieved. en-copyright= kn-copyright= en-aut-name=FujiiMayu en-aut-sei=Fujii en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UenoNanaho en-aut-sei=Ueno en-aut-mei=Nanaho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsudoKoichi en-aut-sei=Mitsudo en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoEisuke en-aut-sei=Sato en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugaSeiji en-aut-sei=Suga en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=166 cd-vols= no-issue=8 article-no= start-page=bqaf102 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neuromedin U Deficiency Disrupts Daily Testosterone Fluctuation and Reduces Wheel-running Activity in Rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=The objective of this study was to elucidate the role of endogenous Neuromedin U (NMU) in rats by performing NMU knockout (KO). Male, but not female NMU KO rats exhibited decreased wheel-running activity vs wildtype (WT), although overall home cage activity was not affected. Plasma testosterone in WT rats varied significantly over the course of a day, with a peak at ZT1 and a nadir at ZT18, whereas in NMU KO rats testosterone remained stable throughout the day. Chronic administration of testosterone restored wheel-running activity in NMU KO rats to the same level as in WT rats, suggesting that the decrease in wheel-running activity in NMU KO rats is due to the disruption of the diurnal change of testosterone. Accordingly, expression of the luteinizing hormone beta subunit (Lhb) mRNA in the pars distalis of anterior pituitary was significantly lower in NMU KO rats; immunostaining revealed that the size of luteinizing hormone (LH)?expressing cells was also relatively small in those animals. In the brain of male WT rats, Nmu was highly expressed in the pars tuberalis, and the NMU receptor Nmur2 was highly expressed in the ependymal cell layer of the third ventricle. This study reveals a novel function of NMU and indicates that endogenous NMU in rats plays a role in the regulation of motivated activity via regulation of testosterone. en-copyright= kn-copyright= en-aut-name=OtsukaMai en-aut-sei=Otsuka en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeuchiYu en-aut-sei=Takeuchi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriyamaMaho en-aut-sei=Moriyama en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EgoshiSakura en-aut-sei=Egoshi en-aut-mei=Sakura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotoYuki en-aut-sei=Goto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GuTingting en-aut-sei=Gu en-aut-mei=Tingting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimuraAtsushi P en-aut-sei=Kimura en-aut-mei=Atsushi P kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaraguchiShogo en-aut-sei=Haraguchi en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=TakeuchiSakae en-aut-sei=Takeuchi en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsuyamaMakoto en-aut-sei=Matsuyama en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=BentleyGeorge E en-aut-sei=Bentley en-aut-mei=George E kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AizawaSayaka en-aut-sei=Aizawa en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Biology, Faculty of Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Department of Biological Sciences, Faculty of Science, Hokkaido University kn-affil= affil-num=8 en-affil=Department of Biochemistry, Showa University School of Medicine kn-affil= affil-num=9 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Division of Molecular Genetics, Shigei Medical Research Institute kn-affil= affil-num=12 en-affil=Department of Integrative Biology and Helen Wills Neuroscience Institute, University of California at Berkeley kn-affil= affil-num=13 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Neuromedin U kn-keyword=Neuromedin U en-keyword=rat kn-keyword=rat en-keyword=motivation kn-keyword=motivation en-keyword=activity kn-keyword=activity en-keyword=testosterone kn-keyword=testosterone en-keyword=wheel-running kn-keyword=wheel-running END start-ver=1.4 cd-journal=joma no-vol=121 cd-vols= no-issue=2 article-no= start-page=232 end-page=243 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Outcomes of allogeneic SCT versus tisagenlecleucel in patients with R/R LBCL and poor prognostic factors en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigated the efficacy of tisagenlecleucel (tisa-cel) and allogeneic hematopoietic stem cell transplantation (allo-SCT) for patients with relapsed and/or refractory (r/r) large B-cell lymphoma (LBCL) with poor prognostic factors, defined as performance status (PS)???2, multiple extranodal lesions (EN), chemorefractory disease, or higher lactate dehydrogenase (LDH). Overall, the allo-SCT group demonstrated worse progression-free survival (PFS), higher non-relapse mortality, and a similar relapse/progression rate. Notably, the tisa-cel group showed better PFS than the allo-SCT group among patients with chemorefractory disease (3.2 vs. 2.0 months, p?=?0.092) or higher LDH (4.0 vs. 2.0 months, p =?0.018), whereas PFS in the two cellular therapy groups was similar among those with PS???2 or multiple EN. Survival time after relapse post-cellular therapy in patients with poor prognostic factors was 1.6 with allo-SCT and 4.6 months with tisa-cel. These findings were confirmed in a propensity score matching cohort. In conclusion, tisa-cel resulted in better survival than allo-SCT in patients with poor prognostic factors. However, patients who relapsed post-cellular therapy had dismal outcomes regardless of therapy. Further strategies are warranted to improve outcomes in these patients. en-copyright= kn-copyright= en-aut-name=HayashinoKenta en-aut-sei=Hayashino en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeraoToshiki en-aut-sei=Terao en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KamoiChihiro en-aut-sei=Kamoi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= en-keyword=Large B-cell lymphoma kn-keyword=Large B-cell lymphoma en-keyword=Allogeneic hematopoietic stem cell transplantation kn-keyword=Allogeneic hematopoietic stem cell transplantation en-keyword=CAR-T cell therapy kn-keyword=CAR-T cell therapy en-keyword=Tisagenlecleucel kn-keyword=Tisagenlecleucel en-keyword=Poor prognostic factors kn-keyword=Poor prognostic factors END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=6 article-no= start-page=388.e1 end-page=388.e14 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=Clinical effects of granulocyte colony-stimulating factor administration and the timing of its initiation on allogeneic hematopoietic cell transplantation outcomes for myelodysplastic syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Granulocyte colony-stimulating factor (G-CSF) accelerates neutrophil recovery after allogeneic hematopoietic cell transplantation (HCT). However, the optimal use of G-CSF and the timing of its initiation after allogeneic HCT for myelodysplastic syndrome (MDS) according to graft type have not been determined. This retrospective study aimed to investigate the effects of using G-CSF administration and the timing of its initiation on transplant outcomes in adult patients with MDS undergoing allogeneic HCT. Using Japanese registry data, we retrospectively investigated the effects of G-CSF administration and the timing of its initiation on transplant outcomes among 4140 adults with MDS after bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), or single-unit cord blood transplantation (CBT) between 2013 and 2022. Multivariate analysis showed that early (days 0 to 4) and late (days 5 to 10) G-CSF administration significantly accelerated neutrophil recovery compared with no G-CSF administration following BMT, PBSCT, and CBT, but there was no benefit of early G-CSF initiation for early neutrophilic recovery regardless of graft type. Late G-CSF initiation was significantly associated with a higher risk of overall chronic GVHD following PBSCT (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.18 to 2.24; P = .002) and CBT (HR, 2.09; 95% CI, 1.21 to 3.60; P = .007) compared with no G-CSF administration. Late G-CSF initiation significantly improved OS compared with no G-CSF administration only following PBSCT (HR, 0.74; 95% CI, 0.58 to 0.94; P = .015). However, G-CSF administration and the timing of its initiation did not affect acute GVHD, relapse, or non-relapse mortality, irrespective of graft type. These results suggest that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT, but increased risk of overall chronic GVHD after PBSCT and CBT. However, the effect of early and late G-CSF initiation on transplant outcomes needs further study in adult patients with MDS. 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=FujiokaMachiko en-aut-sei=Fujioka en-aut-mei=Machiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FuseKyoko en-aut-sei=Fuse en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HosoiHiroki en-aut-sei=Hosoi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasamotoYosuke en-aut-sei=Masamoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=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=IshikawaJun en-aut-sei=Ishikawa en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakamaeHirohisa en-aut-sei=Nakamae en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 ORCID= en-aut-name=MaedaTakeshi en-aut-sei=Maeda en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= en-aut-name=KawamuraKoji en-aut-sei=Kawamura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 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=20 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ItonagaHidehiro en-aut-sei=Itonaga en-aut-mei=Hidehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 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=Department of Hematology, Sasebo City General Hospital kn-affil= affil-num=3 en-affil=Faculty of Medicine, Department of Hematology, Endocrinology and Metabolism, Niigata University kn-affil= affil-num=4 en-affil=Department of Hematology/Oncology, Wakayama Medical University kn-affil= affil-num=5 en-affil=Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital kn-affil= affil-num=6 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=7 en-affil=Department of Hematology, Toranomon Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Kanagawa Cancer Center kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Anjo Kosei Hospital 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 Hematology, Osaka International Cancer Institute kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Hematology, Hokkaido University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Tokai University School of Medicine kn-affil= affil-num=16 en-affil=Department of Hematology and oncology, Kurashiki Central Hospital kn-affil= affil-num=17 en-affil=Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital kn-affil= affil-num=18 en-affil=Department of Hematology, Tottori University Hospital kn-affil= affil-num=19 en-affil=Division of Hematology, Jichi Medical University kn-affil= affil-num=20 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=21 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=22 en-affil=Transfusion and Cell Therapy Unit, Nagasaki University Hospital kn-affil= en-keyword=Granulocyte colony-stimulating factor kn-keyword=Granulocyte colony-stimulating factor en-keyword=Graft-versus-host disease kn-keyword=Graft-versus-host disease en-keyword=Bone marrow transplantation kn-keyword=Bone marrow transplantation en-keyword=Peripheral blood stem cell transplantation kn-keyword=Peripheral blood stem cell transplantation en-keyword=Cord blood transplantation kn-keyword=Cord blood transplantation en-keyword=Myelodysplastic syndrome kn-keyword=Myelodysplastic syndrome END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue=2 article-no= start-page=145 end-page=148 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The trochlea for the intermediate tendon of the digastric muscle: a review en-subtitle= kn-subtitle= en-abstract= kn-abstract=This review explores the novel perspective that the intermediate tendon of the digastric muscle may function as an anatomical trochlear pulley system within the human body, challenging the traditional understanding of trochlear systems. While widely recognized trochlear units include structures like the medial part of the humerus and the superior oblique muscle of the orbit, the review focuses on the unique anatomical arrangement of the intermediate tendon of the digastric muscle in connection with the anterior and posterior bellies of the digastric muscles. Despite current debates within the anatomical community about labeling the digastric muscles as having a trochlea, this paper delves into the scientific definition of a trochlear pulley system, presenting the intermediate tendon of the digastric muscle as a potential trochlea. en-copyright= kn-copyright= en-aut-name=du PlooyXander en-aut-sei=du Plooy en-aut-mei=Xander 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=CardonaJuan J. en-aut-sei=Cardona en-aut-mei=Juan J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TabiraYoko en-aut-sei=Tabira en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BubbKathleen Carol en-aut-sei=Bubb en-aut-mei=Kathleen Carol kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=RaeburnKazzara en-aut-sei=Raeburn en-aut-mei=Kazzara 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= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Tulane University School of Medicine 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 Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine kn-affil= affil-num=4 en-affil=Division of Gross and Clinical Anatomy, Department of Anatomy, Kurume University School of Medicine kn-affil= affil-num=5 en-affil=Anatomy Division, Department of Radiology, Weill Cornell Medical College kn-affil= affil-num=6 en-affil=Department of Anatomical Sciences, St. George’s 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 Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine kn-affil= affil-num=9 en-affil=Department of Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine kn-affil= en-keyword=Digastric muscles kn-keyword=Digastric muscles en-keyword=Intermediate tendon kn-keyword=Intermediate tendon en-keyword=Trochlea kn-keyword=Trochlea en-keyword=Anatomy kn-keyword=Anatomy en-keyword=Fascia kn-keyword=Fascia 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=2025 dt-pub=20250612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sulfur dioxide-induced guard cell death and stomatal closure are attenuated in nitrate/proton antiporter AtCLCa mutants en-subtitle= kn-subtitle= en-abstract= kn-abstract=Guard cells surrounding the stomata play a crucial role in regulating the entrance of hazardous gases such as SO2 into leaves. Stomatal closure could be a plant response to mitigate SO2 damage, although the mechanism for SO2-induced closure remains controversial. Proposed mediators for SO2-induced stomatal closure include phytohormones, reactive oxygen species, gasotransmitters, and cytosolic acidification. In this study, we investigated the mechanism of stomatal closure in Arabidopsis in response to SO2. Despite an increment in auxin and jasmonates after SO2 exposure, the addition of auxin did not cause stomatal closure and jasmonate-insensitive mutants exhibited SO2-induced stomatal closure suggesting auxin and jasmonates are not mediators leading to the closure. In addition, supplementation of scavenging reagents for reactive oxygen species and gasotransmitters did not inhibit SO2-induced closure. Instead, we found that cytosolic acidification is a credible mechanism for SO2-induced stomatal closure in Arabidopsis. CLCa mutants coding H+/nitrate antiporter, involved in cytosolic pH homeostasis, showed less sensitive stomatal phenotype against SO2. These results suggest that cytosolic pH homeostasis plays a tenable role in SO2 response in guard cells. en-copyright= kn-copyright= en-aut-name=OoiLia en-aut-sei=Ooi en-aut-mei=Lia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuuraTakakazu en-aut-sei=Matsuura en-aut-mei=Takakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriIzumi C. en-aut-sei=Mori en-aut-mei=Izumi C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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= en-keyword=airborne pollutants kn-keyword=airborne pollutants en-keyword=cytosolic acidification kn-keyword=cytosolic acidification en-keyword=stomatal closure kn-keyword=stomatal closure en-keyword=sulfur dioxide kn-keyword=sulfur dioxide END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=5 article-no= start-page=733 end-page=747 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A PRA-Rab trafficking machinery modulates NLR immune receptor plasma membrane microdomain anchoring and blast resistance in rice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nucleotide-binding leucine-rich repeat (NLR) receptors mediate pathogen effector-triggered immunity (ETI) in plants, and a subclass of NLRs are hypothesized to function at the plasma membrane (PM). However, how NLR traffic and PM delivery are regulated during immune responses remains largely unknown. The rice NLR PigmR confers broad-spectrum resistance to the blast fungus Magnaporthe oryzae. Here, we report that a PRA (Prenylated Rab acceptor) protein, PIBP4 (PigmR-INTERACTING and BLAST RESISTANCE PROTEIN 4), interacts with both PigmR and the active form of the Rab GTPase, OsRab5a, thereby loads a portion of PigmR on trafficking vesicles that target to PM microdomains. Microdomain-localized PigmR interacts with and activates the small GTPase OsRac1, which triggers reactive oxygen species signaling and hypersensitive response, leading to immune responses against blast infection. Thus, our study discovers a previously unknown mechanism that deploys a PRA-Rab protein delivering hub to ensure ETI, linking the membrane trafficking machinery with NLR function and immune activation in plants. en-copyright= kn-copyright= en-aut-name=LiangDi en-aut-sei=Liang en-aut-mei=Di kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YangDongyong en-aut-sei=Yang en-aut-mei=Dongyong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiTai en-aut-sei=Li en-aut-mei=Tai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhuZhe en-aut-sei=Zhu en-aut-mei=Zhe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanBingxiao en-aut-sei=Yan en-aut-mei=Bingxiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HeYang en-aut-sei=He en-aut-mei=Yang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LiXiaoyuan en-aut-sei=Li en-aut-mei=Xiaoyuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ZhaiKeran en-aut-sei=Zhai en-aut-mei=Keran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=LiuJiyun en-aut-sei=Liu en-aut-mei=Jiyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawanoYoji en-aut-sei=Kawano en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DengYiwen en-aut-sei=Deng en-aut-mei=Yiwen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WuXu Na en-aut-sei=Wu en-aut-mei=Xu Na kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=LiuJunzhong en-aut-sei=Liu en-aut-mei=Junzhong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HeZuhua en-aut-sei=He en-aut-mei=Zuhua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= affil-num=2 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= affil-num=3 en-affil=Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan, Center for Life Sciences, School of Life Sciences, Yunnan University kn-affil= affil-num=4 en-affil=Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan, Center for Life Sciences, School of Life Sciences, Yunnan University kn-affil= affil-num=5 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= affil-num=6 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= affil-num=7 en-affil=School of Life Science and Technology, ShanghaiTech University kn-affil= affil-num=8 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= affil-num=9 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= affil-num=10 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=11 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= affil-num=12 en-affil=Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan, Center for Life Sciences, School of Life Sciences, Yunnan University kn-affil= affil-num=13 en-affil=Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan, Center for Life Sciences, School of Life Sciences, Yunnan University kn-affil= affil-num=14 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= en-keyword=Prenylated Rab acceptor kn-keyword=Prenylated Rab acceptor en-keyword=PigmR kn-keyword=PigmR en-keyword=Trafficking vesicles kn-keyword=Trafficking vesicles en-keyword=OsRab5a kn-keyword=OsRab5a en-keyword=Blast resistance kn-keyword=Blast resistance 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=2025 dt-pub=20250609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The maxillary vein: an anatomical narrative review with clinical implications for oral and maxillofacial surgeons en-subtitle= kn-subtitle= en-abstract= kn-abstract=The maxillary vein, despite its clinical significance, remains underexplored in anatomical literature. It plays a crucial role in venous drainage of the maxillofacial region and is closely associated with surgical procedures such as sagittal split ramus osteotomy, mandibuloplasty, and condylar or parotid surgeries. Due to its variable anatomy and proximity to critical structures, the maxillary vein poses a risk of significant hemorrhage if injured. Its small size and deep location make preoperative identification challenging, especially without contrast-enhanced imaging. Embryologically, the maxillary vein originates from the primitive maxillary vein and develops through complex anastomoses with other craniofacial veins. Anatomical studies have revealed several variations, including the presence of accessory mandibular foramina and unusual venous connections, which may increase surgical risk. Understanding the detailed anatomy and potential variations of the maxillary vein is essential for minimizing complications and improving surgical outcomes. Despite its importance, more anatomical and clinical research is needed to better define its course, variations, and implications in oral and maxillofacial surgery. en-copyright= kn-copyright= en-aut-name=RaeburnKazzara en-aut-sei=Raeburn en-aut-mei=Kazzara 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=TakakuraHiroaki en-aut-sei=Takakura en-aut-mei=Hiroaki 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=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=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SamridRarinthorn en-aut-sei=Samrid en-aut-mei=Rarinthorn kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LoukasMarios en-aut-sei=Loukas en-aut-mei=Marios kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 ORCID= affil-num=1 en-affil=Department of Anatomical Sciences, St. George’s 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 Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 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 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= kn-affil= affil-num=8 en-affil=Department of Anatomical Sciences, St. George’s University kn-affil= affil-num=9 en-affil=Department of Anatomical Sciences, St. George’s University kn-affil= affil-num=10 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= en-keyword=Embryology kn-keyword=Embryology en-keyword=Anatomy kn-keyword=Anatomy en-keyword=Radiology kn-keyword=Radiology en-keyword=Cadaver kn-keyword=Cadaver en-keyword=Mandible kn-keyword=Mandible 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=2025 dt-pub=20250526 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lytic Transglycosylase Deficiency Increases Susceptibility to β-lactam Antibiotics But Reduces Susceptibility to Vancomycin in Escherichia coli en-subtitle= kn-subtitle= en-abstract= kn-abstract=In Staphylococcus aureus, a gram-positive pathogen, vancomycin-resistant strains become susceptible to β-lactam antibiotics, referred to as the “seesaw effect.” However, in gram-negative bacteria, the phenomenon is less clear. Here, we analyzed the gene-knockout effects of eight lytic transglycosylases (slt, mltA, mltB, mltC, mltD, mltE, mltF, mltG) on antibiotic sensitivity in Escherichia coli. Knockout of both slt and mltG increased sensitivity to β-lactam antibiotics and reduced sensitivity to vancomycin. The β-lactam antibiotic sensitivity and vancomycin resistance of the slt-knockout mutant were abolished by the introduction of the wild-type slt gene but remained unchanged by the introduction of the mutant slt gene encoding an amino acid substitution variant of the transglycosylase catalytic centre. The double-knockout strain for slt and mltB was more sensitive to ampicillin and more resistant to vancomycin than each single-knockout strain. The double-knockout strain for slt and mltG was more sensitive to ampicillin and more resistant to vancomycin than each single-knockout strain. These results suggest that loss of lytic transglycosylase activity causes β-lactam antibiotic sensitivity and vancomycin resistance in E. coli. en-copyright= kn-copyright= en-aut-name=KimuraTakahiko en-aut-sei=Kimura en-aut-mei=Takahiko 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=NakagawaRyosuke en-aut-sei=Nakagawa en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FurutaKazuyuki en-aut-sei=Furuta en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KaitoChikara en-aut-sei=Kaito en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Laboratory of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Laboratory of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Laboratory of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Laboratory of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Laboratory of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Escherichia coli kn-keyword=Escherichia coli en-keyword=lytic transglycosylase kn-keyword=lytic transglycosylase en-keyword=seesaw effect kn-keyword=seesaw effect en-keyword=vancomycin kn-keyword=vancomycin en-keyword=β‐lactam antibiotics kn-keyword=β‐lactam antibiotics END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=RP99858 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural basis for molecular assembly of fucoxanthin chlorophyll a/c-binding proteins in a diatom photosystem I supercomplex en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosynthetic organisms exhibit remarkable diversity in their light-harvesting complexes (LHCs). LHCs are associated with photosystem I (PSI), forming a PSI-LHCI supercomplex. The number of LHCI subunits, along with their protein sequences and pigment compositions, has been found to differ greatly among the PSI-LHCI structures. However, the mechanisms by which LHCIs recognize their specific binding sites within the PSI core remain unclear. In this study, we determined the cryo-electron microscopy structure of a PSI supercomplex incorporating fucoxanthin chlorophyll a/c-binding proteins (FCPs), designated as PSI-FCPI, isolated from the diatom Thalassiosira pseudonana CCMP1335. Structural analysis of PSI-FCPI revealed five FCPI subunits associated with a PSI monomer; these subunits were identified as RedCAP, Lhcr3, Lhcq10, Lhcf10, and Lhcq8. Through structural and sequence analyses, we identified specific protein?protein interactions at the interfaces between FCPI and PSI subunits, as well as among FCPI subunits themselves. Comparative structural analyses of PSI-FCPI supercomplexes, combined with phylogenetic analysis of FCPs from T. pseudonana and the diatom Chaetoceros gracilis, underscore the evolutionary conservation of protein motifs crucial for the selective binding of individual FCPI subunits. These findings provide significant insights into the molecular mechanisms underlying the assembly and selective binding of FCPIs in diatoms. en-copyright= kn-copyright= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=XingJian en-aut-sei=Xing en-aut-mei=Jian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KumazawaMinoru en-aut-sei=Kumazawa en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OgawaHaruya en-aut-sei=Ogawa en-aut-mei=Haruya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IfukuKentaro en-aut-sei=Ifuku en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagaoRyo en-aut-sei=Nagao en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=4 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=5 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=8 en-affil=Faculty of Agriculture, Shizuoka University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=18981 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role of galectin-9 in the development of gestational diabetes mellitus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Galectin-9 (Gal-9) is highly expressed in trophoblasts in placenta. Interaction between Gal-9 and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) is important for the differentiation of tissue resident natural killer (trNK) cells in placenta and maintenance of normal pregnancy. Furthermore, the enhanced maternal systemic inflammation associated with increased proinflammatory cytokines in preeclampsia is mediated by enhanced interaction between Gal-9 and Tim-3. However, the role of Gal-9 in gestational diabetes (GDM) remains unexplored. Plasma Gal-9 levels were elevated at 3rd trimester in pregnant women with GDM and positively correlated with placenta and newborn weight. Lgals9 knockout pregnant mice fed with high fat diet (HFD KO) demonstrated maternal glucose intolerance and fetus macrosomia compared with controls (HFD WT). In HFD KO, increased proliferating cells, reduced apoptosis, and autophagy impairment were observed in junctional zones. The number of trNK cells and percentage of Tim-3?+?trNK increased, while early apoptosis percentage in Tim-3?+?trNK was reduced in placenta of HFD KO. The elevation of plasma Gal-9 may be a biomarker for prediction of maternal glucose intolerance and fetal macrosomia in pregnant women with GDM and Gal-9 functions as a compensation factor for GDM by inducing apoptosis in Tim-3?+?trNK cells. en-copyright= kn-copyright= en-aut-name=AlbuayjanHaya Hamed Hassan en-aut-sei=Albuayjan en-aut-mei=Haya Hamed Hassan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeMayu en-aut-sei=Watanabe en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugawaraRyosuke en-aut-sei=Sugawara en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsuyamaEri en-aut-sei=Katsuyama en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiseKoki en-aut-sei=Mise en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OiYukiko en-aut-sei=Oi en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KannoAyaka en-aut-sei=Kanno en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YangBoXuan en-aut-sei=Yang en-aut-mei=BoXuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TaharaToshihisa en-aut-sei=Tahara en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NojimaIchiro en-aut-sei=Nojima en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakatsukaAtsuko en-aut-sei=Nakatsuka en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=EguchiJun en-aut-sei=Eguchi en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 ORCID= en-aut-name=HayataKei 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affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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kn-article= en-subject= kn-subject= en-title=血管内皮細胞、線維芽細胞、およびiPS心筋細胞からなるヒト心臓チップマイクロ生理システム kn-title=Human heart?on?a?chip microphysiological system comprising endothelial cells, fibroblasts, and iPSC?derived cardiomyocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=LIUYUN en-aut-sei=LIU en-aut-mei=YUN kn-aut-name=劉云 kn-aut-sei=劉 kn-aut-mei=云 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=樹状細胞の成熟は、腫瘍由来エクソソームを介してp53搭載腫瘍融解アデノウイルスによって誘導され、全身の抗腫瘍免疫を誘導する kn-title=Dendritic cell maturation is induced by p53?armed oncolytic adenovirus via tumor?derived exosomes enhancing systemic antitumor immunity 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kn-subject= en-title=ヒト臍帯血内皮前駆細胞はラット脳卒中モデルにおける動脈損傷の内膜過形成を緩和する kn-title=Human Cord Blood?Endothelial Progenitor Cells Alleviate Intimal Hyperplasia of Arterial Damage in a Rat Stroke Model en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SUNHONGMING en-aut-sei=SUN en-aut-mei=HONGMING kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=アドレナリンβ2受容体はリガンド非依存的にマスト細胞の IgE 誘導性カルシウム流入を促進する kn-title=Ligand-independent function of β2-adrenergic receptor affects IgE-mediated Ca2+ influx in mast cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NAGAOKei en-aut-sei=NAGAO en-aut-mei=Kei kn-aut-name=長尾圭 kn-aut-sei=長尾 kn-aut-mei=圭 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=p53を搭載した腫瘍融解ウイルス療法は免疫原性細胞死を促進することにより骨肉腫にアブスコパル効果を誘導する kn-title=p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=DEMIYAKoji en-aut-sei=DEMIYA en-aut-mei=Koji kn-aut-name=出宮光二 kn-aut-sei=出宮 kn-aut-mei=光二 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=1 article-no= start-page=vdaf036 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluating short-term survivors of glioblastoma: A proposal based on SEER registry data en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Glioblastomas (GBMs) are central nervous system tumors with a poor prognosis and limited treatment options. Although small subsets of GBM patients survive longer than 3 years, there is little evidence regarding the prognostic factors of GBM. Therefore, we conducted a thorough characterization of GBM in the United States.
Methods: We queried the Surveillance, Epidemiology, and End Results database between 2000 and 2021 to extract age-adjusted incidence rates (AAIRs), age-adjusted mortality rates (AAMRs), and survival data for GBM. We compared trends in AAIR, AAMR, and survival time across age groups 0?14, 15?39, 40?69, and 70+ years. Also, we employed the Fine?Gray competing risk model among short-term survivors (STSs), defined as those with a survival time of 6 months or less, and long-term survivors (LTSs), defined as those with a survival time of 3 years or more.
Results: This study included 60 615 incident GBM cases, 54 998 GBM-specific deaths, and 47 207 GBM patients with available survival time between 2000 and 2021. The mortality-to-incidence ratio was constant among STSs, whereas it increased with age among LTSs. Higher age and male sex were significantly associated with GBM-specific death among LTSs, whereas non-Hispanic White and less intensive treatments were associated with GBM-specific deaths among STSs. Interestingly, higher age was significantly associated with other causes of death among STSs.
Conclusions: STSs partially consist of populations who died from causes other than GBM. It is important to include only GBM-specific deaths in STS groups to conduct reproducible research comparing STSs and LTSs. en-copyright= kn-copyright= en-aut-name=TomitaYusuke en-aut-sei=Tomita en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=OmaeRyo en-aut-sei=Omae en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MizutaRyo en-aut-sei=Mizuta en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirotsuneNobuyuki en-aut-sei=Hirotsune en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Medical School kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurosurgery and Neuroendovascular Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=glioblastoma kn-keyword=glioblastoma en-keyword=long-term survivor kn-keyword=long-term survivor en-keyword=SEER kn-keyword=SEER en-keyword=short-term survivor kn-keyword=short-term survivor en-keyword=United States kn-keyword=United States END start-ver=1.4 cd-journal=joma no-vol=38 cd-vols= no-issue=8 article-no= start-page=100782 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Involvement of PI3K?Akt Signaling in the Clinical and Pathological Findings of Idiopathic Multicentric Castleman Disease?Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis, and Organomegaly and Not Otherwise Specified Subtypes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Idiopathic multicentric Castleman disease is a rare lymphoproliferative disorder that is clinically classified into idiopathic plasmacytic lymphadenopathy (IPL); thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO); and not otherwise specified (NOS). Although each subtype shows varying degrees of hypervascularity, no statistical data on the degree of vascularization have been reported. Additionally, the mechanisms underlying vascularization in each clinical subtype are poorly understood. Here, we aimed to clarify these mechanisms by evaluating the histopathological characteristics of each clinical subtype across 37 patients and performing a whole-transcriptome analysis focusing on angiogenesis-related gene expression. Histologically, TAFRO and NOS exhibited a significantly higher degree of vascularization than IPL (IPL vs TAFRO, P < .001; IPL vs NOS, P = .002). In addition, the germinal centers (GCs) were significantly more atrophic in TAFRO than in IPL. In TAFRO and NOS, “whirlpool vessels” in GCs were seen in most cases (TAFRO, 9/9, 100%; NOS, 6/8, 75%) but not in IPL (IPL vs TAFRO, P < .001; IPL vs NOS, P = .007). Likewise, immunostaining for Ets-related gene revealed higher levels in endothelial cells of GCs in TAFRO than in IPL (P = .014), and TAFRO and NOS were associated with a significantly higher number of endothelial cells in interfollicular areas compared with that in IPL (TAFRO vs IPL, P < .001; NOS vs IPL, P = .002). Gene expression analysis revealed that the PI3K?Akt signaling pathway was significantly enriched in the TAFRO and NOS (TAFRO/NOS) groups. This pathway, which may be activated by vascular endothelial growth factor A and some integrins, is known to affect angiogenesis by increasing vascular permeability, which may explain the clinical manifestations of anasarca and/or fluid retention in TAFRO/NOS. These results suggest that the PI3K?Akt pathway plays an important role in the pathogenesis of TAFRO/NOS. en-copyright= kn-copyright= en-aut-name=HaratakeTomoka en-aut-sei=Haratake en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GonzalezMichael V. en-aut-sei=Gonzalez en-aut-mei=Michael V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LaiYou Cheng en-aut-sei=Lai en-aut-mei=You Cheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OchiSayaka en-aut-sei=Ochi en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsunodaManaka en-aut-sei=Tsunoda en-aut-mei=Manaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FajgenbaumDavid C. en-aut-sei=Fajgenbaum en-aut-mei=David C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=van RheeFrits en-aut-sei=van Rhee en-aut-mei=Frits kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MomoseShuji en-aut-sei=Momose en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Center for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=5 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Medical Biotechnology and Laboratory Science, Chang Gung University kn-affil= affil-num=7 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=9 en-affil=Center for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=10 en-affil=Center for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=11 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=12 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=idiopathic multicentric Castleman disease kn-keyword=idiopathic multicentric Castleman disease en-keyword=integrin subunit alpha 5 kn-keyword=integrin subunit alpha 5 en-keyword=PI3K?Akt signaling pathway kn-keyword=PI3K?Akt signaling pathway en-keyword=platelet-derived growth factor receptor beta kn-keyword=platelet-derived growth factor receptor beta en-keyword=vascular endothelial growth factor A kn-keyword=vascular endothelial growth factor A en-keyword=vascularity kn-keyword=vascularity END start-ver=1.4 cd-journal=joma no-vol=295 cd-vols= no-issue= article-no= start-page=128303 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Using a microfluidic paper-based analytical device and solid-phase extraction to determine phosphate concentration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Phosphate is an essential nutrient, but in high concentrations it contributes to water pollution. Traditional methods for phosphate measurement, such as absorption spectrophotometry and ion chromatography, require expensive equipment and skilled operators. This study introduces a microfluidic paper-based analytical device (μPAD) that is designed to accomplish field-based, low-concentration phosphate measurements. This μPAD utilizes colorimetric detection based on the molybdenum blue method. Herein, we describe how the conditions were optimized in terms of design and sensitivity by adjusting reagent concentrations, paper thickness, and the time frames for sample introduction, and reaction. The operation consists of simply dipping the μPAD into a sample, capturing images in a home-made photo studio box, and processing the images with ImageJ software to measure RGB intensity. An additional preconcentration step involves solid-phase extraction with an anion exchange resin that achieves a 10-fold enrichment, which enables detection that ranges from 0.05 to 1 mg L?1 with a detection limit of 0.089 mg L?1 and a quantification limit of 0.269 mg L?1. The replicated measurements showed good reproducibility both intraday and interday (five different days) as 4.7 % and 3.0 % of relative standard deviations, respectively. After storage in a refrigerator for as long as 26 days, this μPAD delivered stable and accurate results for real-world samples of natural water, soil, and toothpaste. The results produced using this system correlate well with those produced via spectrophotometry. This μPAD-based method is a cost-effective, portable, rapid, and simple approach that allows relatively unskilled operators to monitor phosphate concentrations in field applications. en-copyright= kn-copyright= en-aut-name=DanchanaKaewta en-aut-sei=Danchana en-aut-mei=Kaewta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NambaHaruka en-aut-sei=Namba en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanetaTakashi en-aut-sei=Kaneta en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Chemistry, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry, Okayama University kn-affil= en-keyword=Phosphate kn-keyword=Phosphate en-keyword=Microfluidic paper-based analytical device kn-keyword=Microfluidic paper-based analytical device en-keyword=Solid-phase extraction kn-keyword=Solid-phase extraction en-keyword=Anion exchanger kn-keyword=Anion exchanger en-keyword=Molybdenum blue method kn-keyword=Molybdenum blue method 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=2025 dt-pub=20250519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel method of leukocytapheresis using a highly concentrated sodium citrate solution alternative to acid citrate dextrose solution A en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Large-volume leukocytapheresis is time consuming. The upper limit of the inlet flow rate is determined by the inlet: anticoagulant (AC) ratio and can be changed by combining the AC with heparin. Here, we devised a protocol to increase the AC ratio using a highly concentrated sodium citrate solution without heparin.
Study Design and Methods: We collected data from 40 consecutive apheresis procedures performed using the Spectra Optia system on 40 donors for allogeneic peripheral blood stem cells between June 2022 and June 2023. We used AC containing 2.2% sodium citrate (normal concentrated sodium citrate [NSC]) and 5.32% sodium citrate (highly concentrated sodium citrate [HSC]). The AC ratios were set to 12:1 and 24:1 for the NSC and HSC, respectively.
Results: The processed volume was not different; the maximum inlet flow rate increased, the total processing time was reduced, the AC solution used was reduced, and the product volume was reduced in the HSC group, compared to the NSC group. Although the CD34+ cell CE2 was reduced in the HSC group, no difference was observed in the number of collected CD34+ cells. The incidences of citrate-related reactions were similar.
Discussion: We propose a novel leukocytapheresis method using HSC that shortens the procedure time and reduces the amount of AC solution used compared to the conventional method en-copyright= kn-copyright= en-aut-name=AbeMasaya en-aut-sei=Abe en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkeuchiKazuhiro en-aut-sei=Ikeuchi en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukumiTakuya en-aut-sei=Fukumi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WashioKana en-aut-sei=Washio en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Transfusion and Cell Therapy, Okayama University Hospital kn-affil= affil-num=2 en-affil=Division of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=3 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Transfusion and Cell Therapy, Okayama University Hospital kn-affil= affil-num=5 en-affil=Division of Transfusion and Cell Therapy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Transfusion and Cell Therapy, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pediatric Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Division of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Division of Transfusion and Cell Therapy, Okayama University Hospital kn-affil= en-keyword=anticoagulant kn-keyword=anticoagulant en-keyword=apheresis kn-keyword=apheresis en-keyword=high sodium citrate concentration kn-keyword=high sodium citrate concentration en-keyword=Spectra Optia kn-keyword=Spectra Optia END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=20 article-no= start-page=eadv7488 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250516 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structure of a photosystem I supercomplex from Galdieria sulphuraria close to an ancestral red alga en-subtitle= kn-subtitle= en-abstract= kn-abstract=Red algae exhibit unique photosynthetic adaptations, characterized by photosystem I (PSI) supercomplexes containing light-harvesting complexes (LHCs), forming PSI-LHCI supercomplexes. In this study, we solved the PSI-LHCI structure of Galdieria sulphuraria NIES-3638 at 2.19-angstrom resolution using cryo-electron microscopy, revealing a PSI monomer core associated with seven LHCI subunits. Structural analysis uncovered the absence of phylloquinones, the common secondary electron acceptor in PSI of photosynthetic organisms, suggesting adaptation to a benzoquinone-like molecule. Phylogenetic analysis suggests that G. sulphuraria retains traits characteristic of an ancestral red alga, including distinctive LHCI binding and interaction patterns. Variations in LHCI composition and interactions across red algae, particularly in red-lineage chlorophyll a/b-binding-like protein and red algal LHCs, highlight evolutionary divergence and specialization. These findings not only deepen our understanding of red algal PSI-LHCI diversification but also enable us to predict features of an ancestral red algal PSI-LHCI supercomplex, providing a framework to explore evolutionary adaptations from an ancestral red alga. en-copyright= kn-copyright= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KumazawaMinoru en-aut-sei=Kumazawa en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiTakehiro en-aut-sei=Suzuki en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DohmaeNaoshi en-aut-sei=Dohmae en-aut-mei=Naoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IfukuKentaro en-aut-sei=Ifuku en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagaoRyo en-aut-sei=Nagao en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Research institute for interdisciplinary Science and Graduate School of environ-mental, life, natural Science and technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=3 en-affil=Research institute for interdisciplinary Science and Graduate School of environ-mental, life, natural Science and technology, Okayama University kn-affil= affil-num=4 en-affil=Biomolecular characterization Unit, RiKen center for Sustainable Resource Science kn-affil= affil-num=5 en-affil=Biomolecular characterization Unit, RiKen center for Sustainable Resource Science kn-affil= affil-num=6 en-affil=Research institute for interdisciplinary Science and Graduate School of environ-mental, life, natural Science and technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=8 en-affil=Faculty of Agriculture, Shizuoka University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=4175 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structure of a photosystem II-FCPII supercomplex from a haptophyte reveals a distinct antenna organization en-subtitle= kn-subtitle= en-abstract= kn-abstract=Haptophytes are unicellular algae that produce 30 to 50% of biomass in oceans. Among haptophytes, a subset named coccolithophores is characterized by calcified scales. Despite the importance of coccolithophores in global carbon fixation and CaCO3 production, their energy conversion system is still poorly known. Here we report a cryo-electron microscopic structure of photosystem II (PSII)-fucoxanthin chlorophyll c-binding protein (FCPII) supercomplex from Chyrostila roscoffensis, a representative of coccolithophores. This complex has two sets of six dimeric and monomeric FCPIIs, with distinct orientations. Interfaces of both FCPII/FCPII and FCPII/core differ from previously reported. We also determine the sequence of Psb36, a subunit previously found in diatoms and red algae. The principal excitation energy transfer (EET) pathways involve mainly 5 FCPIIs, where one FCPII monomer mediates EET to CP47. Our findings provide a solid structural basis for EET and energy dissipation pathways occurring in coccolithophores. en-copyright= kn-copyright= en-aut-name=La RoccaRomain en-aut-sei=La Rocca en-aut-mei=Romain kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsaiPi-Cheng en-aut-sei=Tsai en-aut-mei=Pi-Cheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkitaFusamichi en-aut-sei=Akita en-aut-mei=Fusamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3 article-no= start-page=213 end-page=219 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Chromophobe Renal Cell Carcinoma Metastasizing to the Cervical Lymph Nodes after Long-term Follow-up en-subtitle= kn-subtitle= en-abstract= kn-abstract=Renal cell carcinoma (RCC) can metastasize hematogenously and recur after a long dormancy. Chromophobe RCC metastasized to the cervical lymph nodes 10 years after the primary resection in a woman who underwent nephrectomy for RCC (T1aN0M0 stage I). Metastatic RCC diagnosis was confirmed by aspiration. The lymph node mass was resected, and the tumor cells matched chromophobe RCC metastasis. No adjuvant therapy was administered due to the lack of evidence regarding adjuvant therapy for chromophobe RCC. Long-term surveillance is crucial in RCC because of the possibility of late metastasis. We reviewed the clinical aspects and literature on metastatic cervical RCC. en-copyright= kn-copyright= en-aut-name=WatanabeMakoto en-aut-sei=Watanabe en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgawaTomoyuki en-aut-sei=Ogawa en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiKanao en-aut-sei=Kobayashi en-aut-mei=Kanao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsuyaNarutaka en-aut-sei=Katsuya en-aut-mei=Narutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshikawaAkira en-aut-sei=Ishikawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HamamotoTakao en-aut-sei=Hamamoto en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TaharaHiroaki en-aut-sei=Tahara en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UedaTsutomu en-aut-sei=Ueda en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakenoSachio en-aut-sei=Takeno en-aut-mei=Sachio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Otolaryngology, Chugoku Rosai Hospital kn-affil= affil-num=2 en-affil=Department of Otolaryngology, Chugoku Rosai Hospital kn-affil= affil-num=3 en-affil=Department of Nephrology and Urological Surgery, Chugoku Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Molecular Pathology, Graduate School of Medical Sciences, Hiroshima University kn-affil= affil-num=5 en-affil=Department of Molecular Pathology, Graduate School of Medical Sciences, Hiroshima University kn-affil= affil-num=6 en-affil=Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital kn-affil= affil-num=7 en-affil=Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital kn-affil= affil-num=8 en-affil=Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital kn-affil= affil-num=9 en-affil=Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital kn-affil= en-keyword=renal cell carcinoma kn-keyword=renal cell carcinoma en-keyword=cervical lymph node metastasis kn-keyword=cervical lymph node metastasis en-keyword=late recurrence kn-keyword=late recurrence en-keyword=head and neck kn-keyword=head and neck END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3 article-no= start-page=197 end-page=203 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=Rheumatoid Arthritis with Rapid Destructive Arthropathy of the Shoulder due to Calcium Pyrophosphate Deposition en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 67-year-old woman with rheumatoid arthritis presented with an untriggered hematoma in the right shoulder joint. Radiographic findings showed humeral head collapse and destruction of the glenoid fossa with ectopic calcification. Calcium pyrophosphate deposition (CPPD) in the synovial fluid was observed using a polarizing microscope. Histopathological findings revealed chronic inflammatory cell infiltration and giant cells surrounded by CPPD. The patient was diagnosed with rapid destructive arthropathy (RDA). Endoscopic shoulder joint debridement was performed. Postoperatively, active flexion improved from 40 to 75 degrees. This case highlights that CPPD can cause RDA in the shoulder, detectable with detailed histopathology. en-copyright= kn-copyright= en-aut-name=KondoNaoki en-aut-sei=Kondo en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KakutaniRika en-aut-sei=Kakutani en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MochizukiTomoharu en-aut-sei=Mochizuki en-aut-mei=Tomoharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WakuiJunichi en-aut-sei=Wakui en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaoNariaki en-aut-sei=Hao en-aut-mei=Nariaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KinoshitaEiji en-aut-sei=Kinoshita en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawashimaHiroyuki en-aut-sei=Kawashima en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=2 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=3 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=4 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=5 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=6 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=7 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= en-keyword=rheumatoid arthritis kn-keyword=rheumatoid arthritis en-keyword=calcium pyrophosphate deposition kn-keyword=calcium pyrophosphate deposition en-keyword=rapid destructive arthropathy kn-keyword=rapid destructive arthropathy en-keyword=case report kn-keyword=case report END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3 article-no= start-page=167 end-page=176 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=Promising Effectiveness of Combined Chemotherapy and Immunotherapy in Patients with Advanced Non-small Cell Lung Cancer: A Real-World Prospective Observational Study (CS-Lung-003) en-subtitle= kn-subtitle= en-abstract= kn-abstract=This prospective observational study investigated the clinical status of patients with advanced non-small cell lung cancer (NSCLC) treated with cytotoxic chemotherapy+an immune checkpoint inhibitor (chemo + IO) as first-line treatment in a real-world setting. The cases of 98 patients treated with chemo + IO were prospectively collected and analyzed for effectiveness and safety. The response rate to chemo + IO was 46.9%, and the disease control rate was 76.5%. The median progression-free survival and overall survival (OS) in the total population were 5.2 and 22.3 months, respectively. The patients positive for PD-L1 (? 1%) showed significantly longer OS than the negative group (<1%) (median 26.7 vs. 18.7 months, p=0.04). Pre-existing interstitial lung disease (ILD) was associated with shorter OS than the absence of ILD (median 9.0 vs. 22.6 months, p<0.01). Immunerelated adverse events (irAEs) were observed in 28 patients (28.6%). The most frequent irAE was ILD (n=11); Grade 1 (n=1 patient), G2 (n=5), G3 (n=4), and only a single patient with a G5 irAE. In this CS-Lung-003 study, first-line chemo + IO in a real-world setting showed good effectiveness, comparable to that observed in international clinical trials. In real-world practice, chemo + IO is a promising and steadfast strategy. en-copyright= kn-copyright= en-aut-name=KanajiNobuhiro en-aut-sei=Kanaji en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TsubataYukari en-aut-sei=Tsubata en-aut-mei=Yukari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakaoMika en-aut-sei=Nakao en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkunoTakae en-aut-sei=Okuno en-aut-mei=Takae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=TakataKenji en-aut-sei=Takata en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KodaniMasahiro en-aut-sei=Kodani en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamasakiMasahiro en-aut-sei=Yamasaki en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujitakaKazunori en-aut-sei=Fujitaka en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KubotaTetsuya en-aut-sei=Kubota en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=WatanabeNaoki en-aut-sei=Watanabe en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=CS-Lung-003 Investigator en-aut-sei=CS-Lung-003 Investigator en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine kn-affil= affil-num=6 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University kn-affil= affil-num=9 en-affil=Department of Respiratory Disease, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital kn-affil= affil-num=10 en-affil=Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine and Allergology, Kochi University kn-affil= affil-num=12 en-affil=Department of Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=13 en-affil=Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University kn-affil= affil-num=14 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil= kn-affil= en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=real-world kn-keyword=real-world en-keyword=first-line kn-keyword=first-line en-keyword=immune checkpoint inhibitor kn-keyword=immune checkpoint inhibitor en-keyword=combined immunotherapy kn-keyword=combined immunotherapy END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3 article-no= start-page=157 end-page=166 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=Continuous Stimulation with Glycolaldehyde-derived Advanced Glycation End Product Reduces Aggrecan and COL2A1 Production via RAGE in Human OUMS-27 Chondrosarcoma Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chondrocytes are responsible for the production of extracellular matrix (ECM) components such as collagen type II alpha-1 (COL2A1) and aggrecan, which are loosely distributed in articular cartilage. Chondrocyte dysfunction has been implicated in the pathogenesis of rheumatic diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). With age, advanced glycation end products (AGEs) accumulate in all tissues and body fluids, including cartilage and synovial fluid, causing and accelerating pathological changes associated with chronic diseases such as OA. Glycolaldehyde-derived AGE (AGE3), which is toxic to a variety of cell types, have a stronger effect on cartilage compared with other AGEs. To understand the long-term effects of AGE3 on cartilage, we stimulated a human chondrosarcoma cell line (OUMS-27), which exhibits a chondrocytic phenotype, with 10 μg/ml AGE3 for 4 weeks. As a result, the expressions of COL2A1 and aggrecan were significantly downregulated in the OUMS-27 cells without inducing cell death, but the expressions of proteases that play an important role in cartilage destruction were not affected. Inhibition of the receptor for advanced glycation end products (RAGE) suppressed the AGE3-induced reduction in cartilage component production, suggesting the involvement of RAGE in the action of AGE3. en-copyright= kn-copyright= en-aut-name=HatipogluOmer Faruk en-aut-sei=Hatipoglu en-aut-mei=Omer Faruk kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishinakaTakashi en-aut-sei=Nishinaka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YaykasliKursat Oguz en-aut-sei=Yaykasli en-aut-mei=Kursat Oguz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriShuji en-aut-sei=Mori en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeMasahiro en-aut-sei=Watanabe en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ToyomuraTakao en-aut-sei=Toyomura en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=TakahashiHideo en-aut-sei=Takahashi en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University kn-affil= affil-num=2 en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University kn-affil= affil-num=3 en-affil=Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-N?rnberg (FAU) and Universit?tsklinikum Erlangen kn-affil= affil-num=4 en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=5 en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=6 en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=7 en-affil=Department of Translational Research & Dug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University kn-affil= affil-num=10 en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University kn-affil= en-keyword=advanced glycation end product kn-keyword=advanced glycation end product en-keyword=aging kn-keyword=aging en-keyword=cartilage kn-keyword=cartilage en-keyword=collagen kn-keyword=collagen en-keyword=aggrecan kn-keyword=aggrecan END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3 article-no= start-page=147 end-page=155 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=Immunometabolic Regulation of Innate Immunity in Systemic Lupus Erythematosus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pathogens or their components can induce long-lasting changes in the behavior of innate immune cells, a process analogous to “training” for future threats or environmental adaptation. However, such training can sometimes have unintended consequences, such as the development of autoimmunity. Systemic lupus erythematosus (SLE) is a chronic and heterogeneous autoimmune disease characterized by the production of autoantibodies and progressive organ damage. Innate immunity plays a central role in its pathogenesis, contributing through impaired clearance of apoptotic cells, excessive type I interferon production, and dysregulated formation of neutrophil extracellular traps. Recent studies have revealed that metabolites and nucleic acids derived from mitochondria, a crucial energy production site, directly regulate type I interferon and anti-inflammatory cytokine production. These insights have fueled interest in targeting metabolic pathways as a novel therapeutic approach for SLE, offering promise for improving long-term patient outcomes. en-copyright= kn-copyright= en-aut-name=WatanabeHaruki en-aut-sei=Watanabe en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=systemic lupus erythematosus kn-keyword=systemic lupus erythematosus en-keyword=interferon kn-keyword=interferon en-keyword=tricarboxylic acid cycle kn-keyword=tricarboxylic acid cycle en-keyword=innate immune memory kn-keyword=innate immune memory en-keyword=trained immunity kn-keyword=trained immunity END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e202500439 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=2-Hydroxy-3-(Pyrrolidin-1-yl)-Indolines: A Platform for Accessing Decorated Deaminokynurenines Enabled by a Double Tautomeric Control en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this study we introduce indoline hemiaminals as phenacyl bromide surrogates for the synthesis of deaminokynurenine derivatives through cyclic-linear tautomeric intermediates. The reaction proceeds through a tandem process involving the ring opening of indoline hemiaminals, generating transient acyclic aldehydes which are then trapped with in situ generated enolate species. Our protocol overcomes traditional dilemma in production of polar-mismatch 1,4-dicarbonyl compounds by utilizing a transient highly electrophilic linear aldehyde and late-stage transposition of carbonyl moiety. The synthetic utility of our transformation was demonstrated by follow-up transformations, including the first total synthesis of quinoline-2,4-dione alkaloid. en-copyright= kn-copyright= en-aut-name=TokushigeKeisuke en-aut-sei=Tokushige en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AbeTakumi en-aut-sei=Abe en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Deaminokynurenines kn-keyword=Deaminokynurenines en-keyword=Enolates kn-keyword=Enolates en-keyword=Indoline hemiaminals kn-keyword=Indoline hemiaminals en-keyword=Potassium tertbutoxide kn-keyword=Potassium tertbutoxide en-keyword=Tautomerism kn-keyword=Tautomerism 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=2025 dt-pub=20250220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Supplement-induced acute kidney injury reproduced in kidney organoids en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Acute kidney injury associated with the consumption of Beni-koji CholesteHelp supplements, which contain red yeast rice (Beni-Koji), has become a significant public health concern in Japan. While renal biopsy findings from several case reports have suggested tubular damage, no definitive causal relationship has been established, and the underlying mechanisms of kidney injury remain poorly understood. The complexity of identifying toxic substances in supplements containing various bioactive compounds makes conventional investigative approaches both time-consuming and challenging. This highlights an urgent need to establish a reliable platform for assessing organ-specific toxicity in such supplements. In this study, we utilized a kidney organoid model derived from adult rat kidney stem cells (KS cells) to assess the potential tubular toxicity of these supplements. Methods: KS cell clusters were cultured in three-dimensional system supplemented with growth factors to promote kidney organoids. The organoids were subsequently exposed to Beni-koji CholesteHelp supplements or cisplatin, followed by histological and molecular analyses to evaluate structural impacts. Results: Established organoids had the kidney-like structures including tubular-like structures and glomerulus-like structures at the tips of multiple tubules. Treatment with Beni-koji CholesteHelp supplements induced significant tubular damage in the organoids, characterized by epithelial cell thinning, structural disruption, and increase in cleaved-caspase 3-positive apoptotic tubular cells, similar to the organoids treated with cisplatin. Conclusion: These findings provide the first evidence suggesting that certain toxicants in specific batches of Beni-koji CholesteHelp supplements cause direct renal tubular injury. This KS cell-based organoid system represents a cost-effective, reproducible, and technically simple platform for nephrotoxicity screening. en-copyright= kn-copyright= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaraguchiSoichiro en-aut-sei=Haraguchi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Acute kidney injury kn-keyword=Acute kidney injury en-keyword=Drug-induced nephrotoxicity kn-keyword=Drug-induced nephrotoxicity en-keyword=Kidney organoid kn-keyword=Kidney organoid en-keyword=Kidney stem cell kn-keyword=Kidney stem cell END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=18 article-no= start-page=4737 end-page=4741 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250429 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Electrochemical Oxidation of Benzyl Alcohols via Hydrogen Atom Transfer Mediated by 2,2,2-Trifluoroethanol en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a novel electrochemical oxidation of benzyl alcohols. We found that trifluoroethanol plays a role as a hydrogen atom transfer (HAT) mediator, enabling the oxidation of electron-deficient substrates that are difficult to directly oxidize on electrode surfaces. Density functional theory calculations, cyclic voltammetry measurements, and constant potential electrolysis studies supported the proposed HAT mechanism. Moreover, the obtained carbonyl compounds could be functionalized in an electrochemical one-pot manner, further highlighting their synthetic utility. en-copyright= kn-copyright= en-aut-name=KawajiriTakahiro en-aut-sei=Kawajiri en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HosoyaMasahiro en-aut-sei=Hosoya en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GodaSatoshi en-aut-sei=Goda en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoEisuke en-aut-sei=Sato en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugaSeiji en-aut-sei=Suga en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=API R&D Laboratory, Research Division, Shionogi & Co., Ltd. kn-affil= affil-num=2 en-affil=API R&D Laboratory, Research Division, Shionogi & Co., Ltd. kn-affil= affil-num=3 en-affil=API R&D Laboratory, Research Division, Shionogi & Co., Ltd. kn-affil= affil-num=4 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=6 article-no= start-page=97 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250411 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of aged garlic extract on experimental periodontitis in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aged garlic extract (AGE) has been reported to exert anti?inflammatory effects. AGE has been recently found to reduce the inflammatory symptoms of periodontitis, a widespread chronic inflammatory disease caused by oral bacterial infection. However, the mechanisms underlying these effects remain unclear. In the present study, it was aimed to determine the effects of AGE on experimental periodontitis and the related inflammatory factors. AGE (2 g/kg/day) was orally administered to 15 mice during the experimental period, while a control group consisted of 15 mice that received pure water. A total of 3 days after initiation of administration, the left maxillary second molar was ligated with a 5?0 silk thread for 7 days. Blood biochemical tests were performed to monitor the systemic effects of AGE. Alveolar bone loss was measured morphometrically using a stereomicroscope, and reverse transcription?quantitative PCR was performed to assay mRNAs of proinflammatory cytokines in gingival tissues. A histological survey was also performed to identify osteoclasts in periodontitis lesions (five mice per group). The total protein and albumin levels showed no significant differences between the AGE and control groups. However, ligation?induced bone resorption was lower in the AGE group than in the control group (P=0.01). Additionally, ligature increased the mRNA expression of inflammatory cytokines, whereas AGE administration tended to suppress them. Remarkably, tumor necrosis factor gene expression was significantly suppressed (P=0.04). The number of osteoclasts in periodontitis lesions was reduced in the AGE?treated group. These results indicate that AGE prevents alveolar bone loss by suppressing the inflammatory responses related to osteoclast differentiation in the periodontal tissue. Further research is needed to elucidate the role of AGE in reducing inflammatory bone resorption. en-copyright= kn-copyright= en-aut-name=KuangCanyan en-aut-sei=Kuang en-aut-mei=Canyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiraiAnna en-aut-sei=Hirai en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Kamei?ΝagataChiaki en-aut-sei=Kamei?Νagata en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NangoHiroshi en-aut-sei=Nango en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtaniMasahiro en-aut-sei=Ohtani en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Division of Periodontics and Endodontics, Department of Dentistry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Periodontics and Endodontics, Department of Dentistry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Central Research Institute, Wakunaga Pharmaceutical Co., Ltd. kn-affil= affil-num=5 en-affil=Central Research Institute, Wakunaga Pharmaceutical Co., Ltd. kn-affil= affil-num=6 en-affil=Department of Pathophysiology?Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathophysiology?Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=AGE kn-keyword=AGE en-keyword=experimental periodontitis kn-keyword=experimental periodontitis en-keyword=bone resorption kn-keyword=bone resorption en-keyword=inflammation kn-keyword=inflammation en-keyword=osteoclasts kn-keyword=osteoclasts 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=2025 dt-pub=20250429 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparative inhibitory effects of bepotastine and diphenhydramine on rituximab-induced infusion reactions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Infusion-related reaction (IRR) is a common adverse event induced by rituximab. Although first-generation histamine 1 receptor antagonists (H1RAs) are commonly used to prevent IRR, evidence on IRR suppression by the second-generation H1RA bepotastine is scarce. In this study, we assessed the inhibitory effects of bepotastine on rituximab-induced IRR and compared them with those of the first-generation H1RA diphenhydramine.
Methods We retrospectively evaluated IRR incidence in patients with B-cell non-Hodgkin lymphoma who received their first dose of rituximab.
Results The incidence of any grade IRR was 9.8% in the bepotastine group (n?=?92), which was significantly lower than the 30.2% rate in the diphenhydramine group (n?=?96; p? Conclusion Bepotastine may be more effective than diphenhydramine in reducing the incidence of rituximab-induced IRR, particularly low-grade reactions. en-copyright= kn-copyright= en-aut-name=HoriTomoki en-aut-sei=Hori en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakagawaTomoaki en-aut-sei=Nakagawa en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakagawaRinako en-aut-sei=Nakagawa en-aut-mei=Rinako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkayamaMasami en-aut-sei=Okayama en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SudouTamika en-aut-sei=Sudou en-aut-mei=Tamika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamasakiMoe en-aut-sei=Hamasaki en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YasudaMai en-aut-sei=Yasuda en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KobayashiShinya en-aut-sei=Kobayashi en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakamuraFumihiko en-aut-sei=Nakamura en-aut-mei=Fumihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YagiHideo en-aut-sei=Yagi en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=IkushimaShigeki en-aut-sei=Ikushima en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= affil-num=1 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=2 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=4 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=5 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=6 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=7 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=8 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Nara Prefecture General Medical Center kn-affil= affil-num=10 en-affil=Department of Laboratory Medicine, Nara Prefecture General Medical Center kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Nara Prefecture General Medical Center kn-affil= affil-num=12 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=13 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=14 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= en-keyword=Rituximab kn-keyword=Rituximab en-keyword=Infusion reaction kn-keyword=Infusion reaction en-keyword=Bepotastine kn-keyword=Bepotastine en-keyword=Diphenhydramine kn-keyword=Diphenhydramine END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=7 article-no= start-page=193 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Osteosarcoma cell-derived CCL2 facilitates lung metastasis via accumulation of tumor-associated macrophages en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteosarcoma (OS) is the most common malignant tumor of bone in children and adolescents. Although lung metastasis is a major obstacle to improving the prognosis of OS patients, the underlying mechanism of lung metastasis of OS is poorly understood. Tumor-associated macrophages (TAMs) with M2-like characteristics are reportedly associated with lung metastasis and poor prognosis in OS patients. In this study, we investigated the metastasis-associated tumor microenvironment (TME) in orthotopic OS tumor models with non-metastatic and metastatic OS cells. Non-metastatic and metastatic tumor cells derived from mouse OS (Dunn and LM8) and human OS (HOS and 143B) were used to analyze the TME associated with lung metastasis in orthotopic OS tumor models. OS cell-derived secretion factors were identified by cytokine array and enzyme-linked immunosorbent assay (ELISA). Orthotopic tumor models with metastatic LM8 and 143B cells were analyzed to evaluate the therapeutic potential of a neutralizing antibody in the development of primary and metastatic tumors. Metastatic OS cells developed metastatic tumors with infiltration of M2-like TAMs in the lungs. Cytokine array and ELISA demonstrated that metastatic mouse and human OS cells commonly secreted CCL2, which was partially encapsulated in extracellular vesicles. In vivo experiments demonstrated that while primary tumor growth was unaffected, administration of CCL2-neutralizing antibody led to a significant suppression of lung metastasis and infiltration of M2-like TAMs in the lung tissue. Our results suggest that CCL2 plays a crucial role in promoting the lung metastasis of OS cells via accumulation of M2-like TAMs. en-copyright= kn-copyright= en-aut-name=KondoHiroya en-aut-sei=Kondo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KureMiho en-aut-sei=Kure en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DemiyaKoji en-aut-sei=Demiya en-aut-mei=Koji 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=HataToshiaki en-aut-sei=Hata en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 ORCID= en-aut-name=YoshiokaYusuke en-aut-sei=Yoshioka en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=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=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Molecular and Cellular Medicine, Tokyo Medical University kn-affil= affil-num=14 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Osteosarcoma kn-keyword=Osteosarcoma en-keyword=Lung metastasis kn-keyword=Lung metastasis en-keyword=Tumor-associated macrophage kn-keyword=Tumor-associated macrophage en-keyword=CCL2 kn-keyword=CCL2 en-keyword=Extracellular vesicle kn-keyword=Extracellular vesicle END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=9 article-no= start-page=1559 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impacts of Dental Follicle Cells and Periodontal Ligament Cells on the Bone Invasion of Well-Differentiated Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Oral squamous cell carcinoma (OSCC) frequently invades the jawbone, leading to diagnostic and therapeutic challenges. While tumor-bone interactions have been studied, the specific roles of dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) in OSCC-associated bone resorption remain unclear. This study aimed to compare the effects of DFCs and PDLCs on OSCC-induced bone invasion and elucidate the underlying mechanisms. Methods: Primary human DFCs and PDLCs were isolated from extracted third molars and characterized by Giemsa and immunofluorescence staining. An in vitro co-culture system and an in vivo xenograft mouse model were established using the HSC-2 OSCC cell line. Tumor invasion and osteoclast activation were assessed by hematoxylin and eosin (HE) and tartrate-resistant acid phosphatase (TRAP) staining. Immunohistochemical analysis was performed to evaluate the expression of receptor activator of NF-kappa B ligand (RANKL) and parathyroid hormone-related peptide (PTHrP). Results: DFCs significantly enhanced OSCC-induced bone resorption by promoting osteoclastogenesis and upregulating RANKL and PTHrP expression. In contrast, PDLCs suppressed RANKL expression and partially modulated PTHrP levels, thereby reducing osteoclast activity. Conclusions: DFCs and PDLCs exert opposite regulatory effects on OSCC-associated bone destruction. These findings underscore the importance of stromal heterogeneity and highlight the therapeutic potential of targeting specific stromal-tumor interactions to mitigate bone-invasive OSCC. en-copyright= kn-copyright= en-aut-name=ChangAnqi en-aut-sei=Chang en-aut-mei=Anqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=ArashimaTakuma en-aut-sei=Arashima en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= 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=6 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=7 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=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=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= en-keyword=oral squamous cell carcinoma kn-keyword=oral squamous cell carcinoma en-keyword=dental follicle cells kn-keyword=dental follicle cells en-keyword=periodontal ligament cells kn-keyword=periodontal ligament cells en-keyword=bone invasion kn-keyword=bone invasion en-keyword=receptor activator of NF-kappa B ligand kn-keyword=receptor activator of NF-kappa B ligand en-keyword=parathyroid hormone-related peptide kn-keyword=parathyroid hormone-related peptide END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=7 article-no= start-page=192 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=HIF-PH inhibitors induce pseudohypoxia in T cells and suppress the growth of microsatellite stable colorectal cancer by enhancing antitumor immune responses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Recent studies have revealed that CD8+ T cells can be activated via genetic upregulation of HIF-1 alpha, thereby augmenting antitumor effector functions. HIF-1 alpha upregulation can be attained by inhibiting HIF-prolyl hydroxylase (HIF-PH) under normoxic conditions, termed pseudohypoxia. This study investigated whether pseudohypoxia induced by HIF-PH inhibitors suppresses Microsatellite stable (MSS) colorectal cancer (CRC) by affecting tumor immune response.
Methods The HIF-PH inhibitors Roxadustat and Vadadustat were utilized in this study. In vitro, we assessed the effects of HIF-PH inhibitors on human and murine colon cancer cell lines (SW480, HT29, Colon26) and murine T cells. In vivo experiments were performed with mice bearing Colon26 tumors to evaluate the effect of these inhibitors on tumor immune responses. Tumor and spleen samples were analyzed using immunohistochemistry, RT-qPCR, and flow cytometry to elucidate potential mechanisms.
Results HIF-PH inhibitors demonstrated antitumor effects in vivo but not in vitro. These inhibitors enhanced the tumor immune response by increasing the infiltration of CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs). HIF-PH inhibitors induced IL-2 production in splenic and intratumoral CD4+ T cells, promoting T cell proliferation, differentiation, and immune responses. Roxadustat synergistically enhanced the efficacy of anti-PD-1 antibody for MSS cancer by increasing the recruitment of TILs and augmenting effector-like CD8+ T cells.
Conclusion Pseudohypoxia induced by HIF-PH inhibitors activates antitumor immune responses, at least in part, through the induction of IL-2 secretion from CD4+ T cells in the spleen and tumor microenvironment, thereby enhancing immune efficacy against MSS CRC. en-copyright= kn-copyright= en-aut-name=ChenYuehua en-aut-sei=Chen en-aut-mei=Yuehua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=HamadaYusuke en-aut-sei=Hamada en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangYuze en-aut-sei=Wang en-aut-mei=Yuze kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TianMiao en-aut-sei=Tian en-aut-mei=Miao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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=10 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 Pathology and Experimental 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 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 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= affil-num=10 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Colorectal cancer kn-keyword=Colorectal cancer en-keyword=Microsatellite stable kn-keyword=Microsatellite stable en-keyword=Hypoxia-inducible factor kn-keyword=Hypoxia-inducible factor en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=5 article-no= start-page=e70091 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pseudomonas syringae pv. tabaci 6605 Requires Seven Type III Effectors to Infect Nicotiana benthamiana en-subtitle= kn-subtitle= en-abstract= kn-abstract=Type III effectors (T3Es), virulence factors injected into plant cells via the type III secretion system (T3SS), play essential roles in the infection of host plants. Pseudomonas syringae pv. tabaci 6605 (Pta 6605) is the causal agent of wildfire disease in tobacco and harbours at least 22 T3Es in its genome. However, the specific T3Es required by Pta 6605 to infect Nicotiana benthamiana remain unidentified. In this study, we investigated the T3Es that contribute to Pta 6605 infection of N. benthamiana. We constructed Pta 6605 poly-T3E-deficient mutants (Pta DxE) and inoculated them into N. benthamiana. Flood assay, which mimics natural opening-based entry, showed that mutant strains lacking 14-22 T3Es, namely, Pta D14E-D22E mutants, exhibited reduced disease symptoms. By contrast, infiltration inoculation, which involves direct injection into leaves, showed that the Pta D14E to Pta D20E mutants developed disease symptoms. Notably, the Pta D20E, containing AvrE1 and HopM1, induced weak but observable symptoms upon infiltration inoculation. Conversely, no symptoms were observed in either the flood assay or infiltration inoculation for Pta D21E and Pta D22E. Taken together, these findings indicate that the many T3Es such as AvrPto4/AvrPtoB, HopW1/HopAE1, and HopM1/AvrE1 in Pta 6605 collectively contribute to invasion through natural openings and symptom development in N. benthamiana. This study provides the basis for understanding virulence in the host by identifying the minimum T3E repertoire required by Pta 6605 to infect N. benthamiana. 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=NishimuraTakafumi en-aut-sei=Nishimura en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KashiharaSachi en-aut-sei=Kashihara en-aut-mei=Sachi 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=YamamotoMikihiro en-aut-sei=Yamamoto en-aut-mei=Mikihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=ToyodaKazuhiro en-aut-sei=Toyoda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IchinoseYuki en-aut-sei=Ichinose en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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= 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= en-keyword=poly T3E mutant kn-keyword=poly T3E mutant en-keyword=type III effector kn-keyword=type III effector en-keyword=type III secretion system kn-keyword=type III secretion system END start-ver=1.4 cd-journal=joma no-vol=116 cd-vols= no-issue=5 article-no= start-page=1214 end-page=1226 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250227 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High Antigenicity for Treg Cells Confers Resistance to PD-1 Blockade Therapy via High PD-1 Expression in Treg Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Regulatory T (Treg) cells have an immunosuppressive function, and programmed death-1 (PD-1)-expressing Treg cells reportedly induce resistance to PD-1 blockade therapies through their reactivation. However, the effects of antigenicity on PD-1 expression in Treg cells and the resistance to PD-1 blockade therapy remain unclear. Here, we show that Treg cells gain high PD-1 expression through an antigen with high antigenicity. Additionally, tumors with high antigenicity for Treg cells were resistant to PD-1 blockade in vivo due to PD-1+ Treg-cell infiltration. Because such PD-1+ Treg cells have high cytotoxic T lymphocyte antigen (CTLA)-4 expression, resistance could be overcome by combination with an anti-CTLA-4 monoclonal antibody (mAb). Patients who responded to combination therapy with anti-PD-1 and anti-CTLA-4 mAbs sequentially after primary resistance to PD-1 blockade monotherapy showed high Treg cell infiltration. We propose that the high antigenicity of Treg cells confers resistance to PD-1 blockade therapy via high PD-1 expression in Treg cells, which can be overcome by combination therapy with an anti-CTLA-4 mAb. en-copyright= kn-copyright= en-aut-name=MatsuuraHiroaki en-aut-sei=Matsuura en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NinomiyaToshifumi en-aut-sei=Ninomiya en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=TachibanaKota en-aut-sei=Tachibana en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Honobe-TabuchiAkiko en-aut-sei=Honobe-Tabuchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MutoYoshinori en-aut-sei=Muto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, Okayama University kn-affil= affil-num=2 en-affil=Department of Tumor Microenvironment, Okayama University kn-affil= affil-num=3 en-affil=Department of Tumor Microenvironment, Okayama University kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine,Okayama University kn-affil= affil-num=5 en-affil=Department of Dermatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=7 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=8 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=9 en-affil=Department of Tumor Microenvironment, Okayama University 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=Department of Tumor Microenvironment, Okayama University kn-affil= affil-num=13 en-affil=Department of Tumor Microenvironment, Okayama University kn-affil= en-keyword=antigenicity kn-keyword=antigenicity en-keyword=cancer immunotherapy kn-keyword=cancer immunotherapy en-keyword=CTLA-4 kn-keyword=CTLA-4 en-keyword=PD-1 kn-keyword=PD-1 en-keyword=regulatory T cell kn-keyword=regulatory T cell 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=2025 dt-pub=20250430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High-Resolution HPLC for Separating Peptide-Oligonucleotide Conjugates en-subtitle= kn-subtitle= en-abstract= kn-abstract=Peptide-oligonucleotide conjugates (POCs) are chimeric molecules that combine the specificity of oligonucleotides with the functionality of peptides, improving the delivery and therapeutic potential of nucleic acid-based drugs. However, the analysis of POCs, particularly those containing arginine-rich sequences, poses major challenges because of aggregation caused by electrostatic interactions. In this study, we developed an optimized high-performance liquid chromatography (HPLC) method for analyzing POCs. Using a conjugate of DNA and nona-arginine as a model compound, we systematically investigated the effects of various analytical parameters, including column type, column temperature, mobile-phase composition, and pH. A column packed with C18 resin with wide pores combined with butylammonium acetate as the ion-pairing reagent and an optimal column temperature of 80 degrees C provided superior peak resolution and sensitivity. The optimized conditions gave clear separation of POCs from unlinked oligonucleotides and enabled the detection of nucleic acid fragments lacking an alkyne moiety as a linkage part, which is critical for quality control. Our HPLC method is robust and reproducible and substantially reduces the complexity, time, and cost associated with the POC analysis. The method may improve the efficiency of quality control in the production of POCs, thereby supporting their development as promising therapeutic agents for clinical applications. en-copyright= kn-copyright= en-aut-name=NaganumaMiyako en-aut-sei=Naganuma en-aut-mei=Miyako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiGenichiro en-aut-sei=Tsuji en-aut-mei=Genichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AmiyaMisato en-aut-sei=Amiya en-aut-mei=Misato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiraiReira en-aut-sei=Hirai en-aut-mei=Reira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HiguchiYuki en-aut-sei=Higuchi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HataNaoko en-aut-sei=Hata en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NozawaSaoko en-aut-sei=Nozawa en-aut-mei=Saoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeDaishi en-aut-sei=Watanabe en-aut-mei=Daishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakajimaTaeko en-aut-sei=Nakajima en-aut-mei=Taeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=DemizuYosuke en-aut-sei=Demizu en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Organic Chemistry, National Institute of Health Sciences kn-affil= affil-num=2 en-affil=Division of Organic Chemistry, National Institute of Health Sciences kn-affil= affil-num=3 en-affil=YMC CO., LTD. kn-affil= affil-num=4 en-affil=YMC CO., LTD. kn-affil= affil-num=5 en-affil=YMC CO., LTD. kn-affil= affil-num=6 en-affil=YMC CO., LTD. kn-affil= affil-num=7 en-affil=YMC CO., LTD. kn-affil= affil-num=8 en-affil=Division of Organic Chemistry, National Institute of Health Sciences kn-affil= affil-num=9 en-affil=YMC CO., LTD. kn-affil= affil-num=10 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Division of Pharmaceutical Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=214 cd-vols= no-issue= article-no= start-page=32 end-page=41 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Medaka approach to evolutionary social neuroscience en-subtitle= kn-subtitle= en-abstract= kn-abstract=Previously, the integration of comparative biological and neuroscientific approaches has led to significant advancements in social neuroscience. This review highlights the potential and future directions of evolutionary social neuroscience research utilizing medaka fishes (the family Adrianichthyidae) including Japanese medaka (Oryzias latipes). We focus on medaka social cognitive capabilities and mate choice behavior, particularly emphasizing mate preference using visual cues. Medaka fishes are also advantageous due to their abundant genetic resources, extensive genomic information, and the relative ease of laboratory breeding and genetic manipulation. Here we present some research examples of both the conventional neuroscience approach and evolutionary approach involving medaka fishes and other species. We also discuss the prospects of uncovering the molecular and cellular mechanisms underlying the diversity of visual mate preference among species. Especially, we introduce that the single-cell transcriptome technology, particularly in conjunction with 'Adaptive Circuitry Census', is an innovative tool that bridges comparative biological methods and neuroscientific approaches. Evolutionary social neuroscience research using medaka has the potential to unveil fundamental principles in neuroscience and elucidate the mechanisms responsible for generating diversity in mating strategies. en-copyright= kn-copyright= en-aut-name=AnsaiSatoshi en-aut-sei=Ansai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Hiraki-KajiyamaTowako en-aut-sei=Hiraki-Kajiyama en-aut-mei=Towako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UedaRyutaro en-aut-sei=Ueda en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekiTakahide en-aut-sei=Seki en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YokoiSaori en-aut-sei=Yokoi en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatsumuraTakafumi en-aut-sei=Katsumura en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeuchiHideaki en-aut-sei=Takeuchi en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=3 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=4 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=5 en-affil=School of Pharmaceutical Sciences, Hokkaido University kn-affil= affil-num=6 en-affil=School of Medicine, Kitasato University kn-affil= affil-num=7 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= en-keyword=Evolutionary neuroscience kn-keyword=Evolutionary neuroscience en-keyword=Comparative neuroscience kn-keyword=Comparative neuroscience en-keyword=Medaka bioresource kn-keyword=Medaka bioresource en-keyword=Visual mate preference kn-keyword=Visual mate preference en-keyword=Sexual selection kn-keyword=Sexual selection en-keyword=Genetic manipulation kn-keyword=Genetic manipulation END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=1 article-no= start-page=15 end-page=19 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=The potential and prospects of organ generation medicine kn-title=臓器創造・移植医療の可能性と展望 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MoriMunemasa en-aut-sei=Mori en-aut-mei=Munemasa kn-aut-name=森宗昌 kn-aut-sei=森 kn-aut-mei=宗昌 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Organ Generation and Biomedical Engineering, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学学術研究院医歯薬域　臓器創造医療・生命医工学 en-keyword=organ generation kn-keyword=organ generation en-keyword=regeneration kn-keyword=regeneration en-keyword=bioengineering kn-keyword=bioengineering END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=2 article-no= start-page=e70091 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250427 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Olanzapine enabled rechallenge after lorlatinib-induced psychosis: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Lorlatinib is a third-generation tyrosine kinase inhibitor for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). While it has a high intracranial lesion control rate, it can also cause central nervous system complications, including psychotic symptoms. We present a case of lorlatinib-induced psychosis successfully managed with olanzapine, enabling lorlatinib rechallenge.
Case Presentation: A 32-year-old woman with ALK-positive NSCLC and brain metastases was started on lorlatinib. After 18 months, she developed hallucinations and delusions. Despite treatment with risperidone, her psychotic symptoms persisted, leading to hospitalization. Her symptoms resolved upon lorlatinib discontinuation while risperidone was continued. Given the critical role of lorlatinib in controlling brain metastases, rechallenge was considered. To mitigate concerns regarding drug interactions, risperidone was replaced with olanzapine. Following lorlatinib rechallenge with olanzapine, no recurrence of psychiatric symptoms was observed, allowing continued lorlatinib treatment. Additionally, no progression of lung cancer was noted.
Conclusion: Lorlatinib is an essential drug for controlling brain metastases in ALK-positive NSCLC. However, it can induce psychotic symptoms. When psychiatrists are involved in managing adverse effects during cancer treatment, close collaboration among oncologists, psychiatrists, and patients is essential. en-copyright= kn-copyright= en-aut-name=YokodeAkiyoshi en-aut-sei=Yokode en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraYuko en-aut-sei=Nakamura en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakamotoShinji en-aut-sei=Sakamoto en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine,Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=psycho-oncology kn-keyword=psycho-oncology en-keyword=lorlatinib kn-keyword=lorlatinib en-keyword=lung cancer kn-keyword=lung cancer en-keyword=medication-induced psychosis kn-keyword=medication-induced psychosis END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=1 article-no= start-page=4 end-page=6 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=The 2023 Incentive Award of the Okayama Medical Association in General Medical Science (2023 Yuuki Prize) kn-title=令和５年度岡山医学会賞　総合研究奨励賞（結城賞） en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SumiiYuichi en-aut-sei=Sumii en-aut-mei=Yuichi kn-aut-name=住居優一 kn-aut-sei=住居 kn-aut-mei=優一 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=岡山大学大学院医歯薬学総合研究科　血液・腫瘍・呼吸器内科学 END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=1 article-no= start-page=1 end-page=15 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250331 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Improved sedimentary layer model including the accretionary prism in the fore-arc region of the Ryukyu arc, Japan kn-title=南西諸島の前弧域における付加体を含む堆積層のモデル化 en-subtitle= kn-subtitle= en-abstract= kn-abstract=　We combine the recent seismic reflection profiles to construct a new seismic velocity model of the sedimentary layer incorporating the accretionary prism along the Ryukyu trench. In constructing the new model, we refer to the zoning (ZONE1 to ZONE4) identified by Okamura et al. (2017, Tectonophys.). The construction process consists of the following steps: First, we digitize either unconformities or VP=4 to 5 km/s lines as the seismic basement, whichever is more clearly identifiable. Second, the digitized thickness data of the sedimentary layer from the reflection profiles are geometrically modeled and interpolated to make the three-dimensional structure model. Finally, we supplement the external region of the constructed 3-D sedimentary model using the J-SHIS model provided by the NIED to complete the velocity structure model in the entire Ryukyu arc. The main features of our model are as follows: In ZONE1, off Ishigaki-jima island, the thick sedimentary layer extends about 50 km wide from the Ryukyu trench. In ZONE2, off Miyako-jima island, the thinner layer compared to the other zones is found near the trench, with a thin sedimentary terrace covering the area behind it. In ZONE3, off Okinawa-jima island, the sedimentary layer deepens as it approaches the trench. In ZONE4, off Tokara islands, the deepest layer among all zones is identified. We then conduct 3-D finite-difference simulations of seismic wave propagation using the new and the previous models to confirm the improvement of the new model. In the simulations, the effects of the accretionary prism along the Ryukyu trench on the seismic wave propagation are clearly identified. en-copyright= kn-copyright= en-aut-name=KOMATSUMasanao en-aut-sei=KOMATSU en-aut-mei=Masanao kn-aut-name=小松正直 kn-aut-sei=小松 kn-aut-mei=正直 aut-affil-num=1 ORCID= en-aut-name=URAKAMISohei en-aut-sei=URAKAMI en-aut-mei=Sohei kn-aut-name=浦上想平 kn-aut-sei=浦上 kn-aut-mei=想平 aut-affil-num=2 ORCID= en-aut-name=OKAMOTOTaro en-aut-sei=OKAMOTO en-aut-mei=Taro kn-aut-name=岡元太郎 kn-aut-sei=岡元 kn-aut-mei=太郎 aut-affil-num=3 ORCID= en-aut-name=TAKENAKAHiroshi en-aut-sei=TAKENAKA en-aut-mei=Hiroshi kn-aut-name=竹中博士 kn-aut-sei=竹中 kn-aut-mei=博士 aut-affil-num=4 ORCID= affil-num=1 en-affil=Okayama Gakuin University kn-affil=岡山学院大学 affil-num=2 en-affil=Formerly Department of Earth Sciences, Okayama University kn-affil=元・岡山大学大学院自然科学研究科 affil-num=3 en-affil=Department of Earth and Planetary Sciences, School of Science, Institute of Science Tokyo kn-affil=東京科学大学理学院地球惑星科学系 affil-num=4 en-affil=Department of Earth Sciences, Okayama University kn-affil=岡山大学学術研究院環境生命自然科学学域 en-keyword=Sedimentary layer model kn-keyword=Sedimentary layer model en-keyword=Accretionary prism kn-keyword=Accretionary prism en-keyword=Ryukyu arc kn-keyword=Ryukyu arc END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=2 article-no= start-page=e70108 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250421 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A case report of ineffective electroconvulsive therapy for chronic pain en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Somatic symptom disorder (SSD), which includes chronic pain, is a common mental disorder characterized by significant functional impairment and other psychiatric comorbidities. Electroconvulsive therapy (ECT) has been proposed as a potential treatment for refractory chronic pain. However, evidence supporting its efficacy is limited and/or low quality. We present a case of SSD with chronic pain in which ECT was ineffective.
Case Presentation: The patient was a 63-year-old man with chronic pain in the lower back, buttocks, thighs, and soles of the feet. The duration of his chronic pain was 3.8 years. He was diagnosed with Bertolotti's syndrome and SSD. He did not meet the criteria for major depressive disorder. He kept physically active by walking and doing exercises to distract himself from his pain. He strongly perceived pain as a physical issue and preferred ECT over psychotherapy. Despite undergoing 10 ECT sessions with adequate seizures, his pain persisted. After four sessions, he experienced despair over the lack of improvement in pain, which temporarily intensified his suicidal ideation. After undergoing ECT, he continued to maintain his activities, including walking and exercise, while his catastrophic thinking about pain persisted.
Conclusion: The ineffectiveness of ECT in this case highlights the need for balanced counseling, particularly for patients who consider ECT a last-resort treatment. Psychological monitoring and depression screening are essential, especially given the risk of heightened despair or suicidal ideation when ECT is ineffective. Therefore, collaborative decision-making based on accurate information is vital. en-copyright= kn-copyright= en-aut-name=FukaoTakashi en-aut-sei=Fukao en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaYuto en-aut-sei=Yamada en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AsadaKazushi en-aut-sei=Asada en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AsadaTakahiro en-aut-sei=Asada en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=RiHirotoshi en-aut-sei=Ri en-aut-mei=Hirotoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakamotoShinji en-aut-sei=Sakamoto en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=chronic pain kn-keyword=chronic pain en-keyword=electroconvulsive therapy kn-keyword=electroconvulsive therapy en-keyword=pain disorder kn-keyword=pain disorder en-keyword=somatic symptom disorder kn-keyword=somatic symptom disorder END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=1 article-no= start-page=36 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=Anticoagulant effects of edoxaban in cancer and noncancer patients with venous thromboembolism en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Edoxaban, a direct oral anticoagulant (DOAC), is a first-line treatment for venous thromboembolism (VTE) and the suppression of VTE recurrence. In patients with cancer, however, recurrent VTE after DOAC treatment may be more common than in noncancer patients. To evaluate our hypothesis that the anticoagulation effect of edoxaban is lower in VTE patients with cancer than in noncancer patients.
Methods This study was a prospective, multicenter, observational study including patients treated with edoxaban for VTE in Japan. The primary outcome was the difference in the prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer level at 5 h after initial edoxaban administration between the cancer and noncancer groups. An additional outcome was the longitudinal change in PT and APTT from 5 h to overnight after edoxaban administration. The incidence of adverse events was further investigated.
Results PT and APTT at 5 h after initial edoxaban administration were not significantly different between the cancer (n = 84) and noncancer groups (n = 138) (e.g., log-transformed APTT 3.55 vs. 3.55, p = 0.45). However, D-dimer in the cancer groups was significantly greater than that in the noncancer groups (log-transformed 1.83 vs. 1.79, p = 0.009). PT and APTT significantly decreased from 5 h to overnight after edoxaban, but a similar pattern was observed in each group. All adverse events after edoxaban administration were also similar between patients with cancer and noncancer.
Conclusion PT and APTT after edoxaban administration were similar between VTE patients with cancer and noncancer groups, suggesting that edoxaban has anticoagulation effects on cancer-associated VTE similar to those of noncancer patients.
Trial registration UMIN000041973; Registration Date: 2020.10.5. en-copyright= kn-copyright= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuoNaoaki en-aut-sei=Matsuo en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaitoTakanori en-aut-sei=Naito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurodaKazuhiro en-aut-sei=Kuroda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TokiokaKoji en-aut-sei=Tokioka en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HatanakaKunihiko en-aut-sei=Hatanaka en-aut-mei=Kunihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujimotoRyohei en-aut-sei=Fujimoto en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamaokaHidenaru en-aut-sei=Yamaoka en-aut-mei=Hidenaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KajikawaYutaka en-aut-sei=Kajikawa en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SurugaKazuki en-aut-sei=Suruga en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SugiyamaHiroki en-aut-sei=Sugiyama en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MiyajiTsuyoshi en-aut-sei=Miyaji en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MorimotoYoshimasa en-aut-sei=Morimoto en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OkamuraNobuhiro en-aut-sei=Okamura en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SarashinaToshihiro en-aut-sei=Sarashina en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 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=21 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama City Hospital kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama Rosai Hospital kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, NHO Fukuyama Medical Center kn-affil= affil-num=11 en-affil=Department of Cardiovascular Medicine, Okayama Medical Center kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=13 en-affil=Hosogi Hospital kn-affil= affil-num=14 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=15 en-affil=Okamura Isshindow Hospital kn-affil= affil-num=16 en-affil=Kuroda Clinic kn-affil= affil-num=17 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School kn-affil= affil-num=21 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Factor Xa inhibitors kn-keyword=Factor Xa inhibitors en-keyword=Anticoagulation effects kn-keyword=Anticoagulation effects en-keyword=Cancer kn-keyword=Cancer en-keyword=Venous thromboembolism kn-keyword=Venous thromboembolism END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=116 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=ADAR1-high tumor-associated macrophages induce drug resistance and are therapeutic targets in colorectal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Colorectal cancer (CRC) is considered the third most common type of cancer worldwide. Tumor-associated macrophages (TAMs) have been shown to promote drug resistance. Adenosine-to-inosine RNA-editing, as regulated by adenosine deaminase acting on RNA (ADAR), is a process that induces the posttranscriptional modification of critical oncogenes. The aim of this study is to determine whether the signals from cancer cells would induce RNA-editing in macrophages.
Methods The effects of RNA-editing on phenotypes in macrophages were analyzed using clinical samples and in vitro and in vivo models.
Results The intensity of the RNA-editing enzyme ADAR1 (Adenosine deaminase acting on RNA 1) in cancer and mononuclear cells indicated a strong positive correlation between the nucleus and cytoplasm. The ADAR1-positive mononuclear cells were positive for CD68 and CD163, a marker for M2 macrophages. Cancer cells transport pro-inflammatory cytokines or ADAR1 protein directly to macrophages via the exosomes, promoting RNA-editing in AZIN1 (Antizyme Inhibitor 1) and GLI1 (Glioma-Associated Oncogene Homolog 1) and resulting in M2 macrophage polarization. GLI1 RNA-editing in the macrophages induced by cancer cells promotes the secretion of SPP1, which is supplied to the cancer cells. This activates the NF kappa B pathway in cancer cells, promoting oxaliplatin resistance. When the JAK inhibitors were administered, oncogenic RNA-editing in the macrophages was suppressed. This altered the macrophage polarization from M2 to M1 and decreased oxaliplatin resistance in cancer cells.
Conclusions This study revealed that ADAR1-high TAMs are crucial in regulating drug resistance in CRC and that targeting ADAR1 in TAMs could be a promising treatment approach for overcoming drug resistance in CRC. en-copyright= kn-copyright= en-aut-name=UmedaHibiki en-aut-sei=Umeda en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriwakeKazuya en-aut-sei=Moriwake en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=YoshidaKazuhiro en-aut-sei=Yoshida en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakedaSho en-aut-sei=Takeda en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YanoShuya en-aut-sei=Yano en-aut-mei=Shuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=KishimotoHiroyuki en-aut-sei=Kishimoto en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=KayanoMasashi en-aut-sei=Kayano en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= en-aut-name=MoriYoshiko en-aut-sei=Mori en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 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=21 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=22 ORCID= en-aut-name=GoelAjay en-aut-sei=Goel en-aut-mei=Ajay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 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=24 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= 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= affil-num=13 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=17 en-affil=Department of Obstetrics and Gynecology, Okayama University Gradu?ate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=22 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute, City of Hope Comprehensive Cancer Center kn-affil= affil-num=24 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=RNA-editing kn-keyword=RNA-editing en-keyword=Macrophage kn-keyword=Macrophage en-keyword=Chemoresistance kn-keyword=Chemoresistance en-keyword=Biomarker kn-keyword=Biomarker en-keyword=Colorectal cancer kn-keyword=Colorectal cancer END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=8 article-no= start-page=e70793 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=Genomic Differences and Distinct TP53 Mutation Site-Linked Chemosensitivity in Early- and Late-Onset Gastric Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Gastric cancer (GC) in younger patients often exhibits aggressive behavior and a poorer prognosis than that in older patients. Although the clinical differences may stem from oncogenic gene variations, it is unclear whether genetic differences exist between these groups. This study compared the genetic profiles of early- and late-onset GC and evaluated their impact on treatment outcomes.
Methods: We analyzed genetic data from 1284 patients with GC in the Japanese nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, comparing early-onset (<= 39 years; n = 143) and late-onset (>= 65 years; n = 1141) groups. The influence of TP53 mutations on the time to treatment failure (TTF) with platinum-based chemotherapy and the sensitivity of cancer cells with different TP53 mutation sites to oxaliplatin were assessed in vitro.
Results: Early- and late-onset GC showed distinct genetic profiles, with fewer neoantigen-associated genetic changes observed in early-onset cases. In particular, TP53 has distinct mutation sites; R175H and R273 mutations are more frequent in early- and late-onset GC, respectively. The R175H mutation showed higher sensitivity to oxaliplatin in vitro, consistent with the longer TTF in early-onset patients (17.3 vs. 7.0 months, p = 0.013) when focusing on the patients with TP53 mutations.
Conclusion: Genomic differences, particularly in TP53 mutation sites, between early- and late-onset GC support the need for age-specific treatment strategies. en-copyright= kn-copyright= en-aut-name=KamioTomohiro en-aut-sei=Kamio en-aut-mei=Tomohiro 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=HirosunaKensuke en-aut-sei=Hirosuna en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OzatoToshiki en-aut-sei=Ozato en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=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, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=early-onset gastric cancer kn-keyword=early-onset gastric cancer en-keyword=oxaliplatin kn-keyword=oxaliplatin en-keyword=TP53 kn-keyword=TP53 END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=4 article-no= start-page=e70151 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=Frequency and Characteristics of Gastrointestinal Diseases in Patients With Neurofibromatosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aim: Patients with neurofibromatosis (NF) frequently experience gastrointestinal symptoms, but the specific characteristics of these lesions are not well understood.
Methods: To investigate the prevalence and nature of gastrointestinal diseases in this population, we analyzed the gastrointestinal lesions identified through endoscopic examinations in patients with NF.
Results: We included 225 patients with NF type 1 (NF1) and 15 with NF type 2 (NF2). None of the NF2 patients underwent endoscopy. Among the NF1 patients, 27 received endoscopies, and 13 (59%) had gastrointestinal lesions. These 13 patients were predominantly male (10 males and three females), with a median age of 53 years (range: 19-76 years). The identified lesions included colorectal polyps (n = 6), gastrointestinal stromal tumors ([GIST], n = 4), subepithelial lesions (n = 3), gastric fundic gland polyps (n = 3), diffuse intestinal ganglioneuromatosis (n = 2), esophageal polyps (n = 2), a Schwann cell hamartoma (n = 1), esophageal cancer (n = 1), and a gastric hyperplastic polyp (n = 1). All GISTs and one case of diffuse intestinal ganglioneuromatosis were surgically resected. Interestingly, six out of 13 patients were asymptomatic. Additionally, all patients who required surgery were 40 years of age or older.
Conclusions: These findings suggest that routine endoscopic examinations, along with imaging techniques like computed tomography and magnetic resonance imaging, could be beneficial for the early detection of gastrointestinal lesions in NF1 patients aged 40 and above. en-copyright= kn-copyright= en-aut-name=HondaManami en-aut-sei=Honda en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya 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=YamasakiYasushi en-aut-sei=Yamasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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 Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathology, 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= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Practical Gastrointestinal Endoscopy,Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=colonoscopy kn-keyword=colonoscopy en-keyword=esophagogastroduodenoscopy kn-keyword=esophagogastroduodenoscopy en-keyword=gastrointestinal neoplasms kn-keyword=gastrointestinal neoplasms en-keyword=gastrointestinal stromal tumor kn-keyword=gastrointestinal stromal tumor en-keyword=neurofibromatosis kn-keyword=neurofibromatosis END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=139 end-page=144 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=Safe Resection of Esophageal Cancer with a Non-Recurrent Inferior Laryngeal Nerve Associated with an Aberrant Right Subclavian Artery Using Intraoperative Nerve Monitoring en-subtitle= kn-subtitle= en-abstract= kn-abstract=In thoracic esophageal cancer, lymph node dissection around the recurrent laryngeal nerve is crucial but poses a risk of nerve palsy, affecting postoperative quality of life. In cases with an aberrant right subclavian artery (ARSA), the right recurrent laryngeal nerve is absent, and the non-recurrent inferior laryngeal nerve (NRILN) enters the larynx directly from the vagus nerve in the cervical region. Identifying the course of the NRILN is vital to avoid injury. A case of esophageal cancer with an ARSA, in which the course of the NRILN was preserved using the Nerve Integrity Monitoring (NIM) system during surgery, is described. en-copyright= kn-copyright= en-aut-name=TakedaYasushige en-aut-sei=Takeda en-aut-mei=Yasushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=MizusawaYohei en-aut-sei=Mizusawa en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoHijiri en-aut-sei=Matsumoto en-aut-mei=Hijiri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KondoYuhei en-aut-sei=Kondo en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KunitomoTomoyoshi en-aut-sei=Kunitomo en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanoueYukinori en-aut-sei=Tanoue en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=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=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=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, 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=esophageal cancer kn-keyword=esophageal cancer en-keyword=intraoperative nerve monitoring kn-keyword=intraoperative nerve monitoring en-keyword=aberrant right subclavian artery kn-keyword=aberrant right subclavian artery en-keyword=non-recurrent inferior laryngeal nerve kn-keyword=non-recurrent inferior laryngeal nerve en-keyword=thoracoscopic esophagectomy kn-keyword=thoracoscopic esophagectomy END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=129 end-page=134 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=A Case of Retinitis Pigmentosa Diagnosed with Severe Anterior Capsule Contraction after Cataract Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 66-year-old woman presented with significant anterior capsule contraction and intraocular lens dislocation in both eyes 4 months after cataract surgery. Postoperative examinations such as fluorescein angiography, Goldmann perimetry, and electroretinography revealed retinitis pigmentosa (RP). Patients with significant anterior capsule contraction after cataract surgery should be closely examined because RP may be a contributing factor. en-copyright= kn-copyright= en-aut-name=TsujiAkihiro en-aut-sei=Tsuji en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraShuhei en-aut-sei=Kimura en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HosokawaMio en-aut-sei=Hosokawa en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiKosuke en-aut-sei=Takahashi en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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= affil-num=7 en-affil=Fukuyama City Hospital, Fukuyama City kn-affil= affil-num=8 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=retinitis pigmentosa kn-keyword=retinitis pigmentosa en-keyword=intraocular lens kn-keyword=intraocular lens en-keyword=anterior capsule contraction kn-keyword=anterior capsule contraction END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=117 end-page=121 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=From a Congenital Defect to Cancer: A Case of Squamous Cell Carcinoma in a Neglected Myelomeningocele en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neural tube defects are common congenital anomalies, typically presenting early due to visible swelling and/or neurological deficits. Rarely, cystic swellings are neglected until adulthood, with only 14 cases of malignancy developing in an untreated meningomyelocele reported to date. We describe the case details of a 26-year-old Indian woman with this rare complication. Magnetic resonance imaging revealed a low-lying spinal cord with spinal dysraphism, cord herniation, and a cystic lesion. The biopsy confirmed a well-differentiated squamous cell carcinoma. Malignant transformation in an untreated myelomeningocele is rare, with chronic irritation and infection as proposed causes. Early biopsy and treatment are crucial for its management. en-copyright= kn-copyright= en-aut-name=GautamAbhishek en-aut-sei=Gautam en-aut-mei=Abhishek kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KenawadekarRahul en-aut-sei=Kenawadekar en-aut-mei=Rahul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HattiholiVirupaxi en-aut-sei=Hattiholi en-aut-mei=Virupaxi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MastePraful Suresh en-aut-sei=Maste en-aut-mei=Praful Suresh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Neurosurgery, Jawaharlal Nehru Medical College, KAHER kn-affil= affil-num=2 en-affil=Department of General Surgery, Jawaharlal Nehru Medical College, KAHER kn-affil= affil-num=3 en-affil=Department of Radiology, Jawaharlal Nehru Medical College, KAHER kn-affil= affil-num=4 en-affil=Department of Neurosurgery, Jawaharlal Nehru Medical College, KAHER kn-affil= en-keyword=squamous cell carcinoma kn-keyword=squamous cell carcinoma en-keyword=meningomyelocele kn-keyword=meningomyelocele en-keyword=occult spinal dysraphism kn-keyword=occult spinal dysraphism END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=109 end-page=116 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=Relationship between Personality Traits and Postpartum Depressive Symptoms in Women who Became Pregnant via Infertility Treatment en-subtitle= kn-subtitle= en-abstract= kn-abstract=The status of postpartum depression was elucidated herein with the use of the Edinburgh Postnatal Depression Scale (EPDS) in women in Shikoku, Japan who became pregnant and gave birth after undergoing infertility treatment, including assisted reproductive technology (ART). The assessment was performed during their children’s 4-month health examination. The relationships between postpartum depression and the mothers’ background factors and scores on the Big Five personality traits scale were also examined. Of the Big Five personality traits, the scores for neuroticism were significantly higher in the ART group (n=71) than in the general infertility treatment (n=118) and natural pregnancy (n=872) groups. No significant differences in EPDS scores were seen among these three groups. A logistic regression analysis showed that neuroticism was associated with an EPDS score ≧9 points, (which is suggestive of postpartum depression, ) in all groups. Moreover, although a long-standing marriage had an inhibitory effect on postpartum depression in the natural pregnancy group, no such trend was seen in the ART group, which included many women with long-standing marriages. Particularly for women who become pregnant by ART, an individualized response that pays close attention to the woman’s personality traits is needed. en-copyright= kn-copyright= en-aut-name=AwaiKyoko en-aut-sei=Awai en-aut-mei=Kyoko 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=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Health Sciences, Okayama University kn-affil= en-keyword=infertility treatment kn-keyword=infertility treatment en-keyword=assisted reproductive technology kn-keyword=assisted reproductive technology en-keyword=postpartum kn-keyword=postpartum en-keyword=postpartum depression kn-keyword=postpartum depression en-keyword=personality trait kn-keyword=personality trait END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=93 end-page=100 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=Lower Work Engagement Is Associated with Insomnia, Psychological Distress, and Neck Pain among Junior and Senior High School Teachers in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=School teachers are subject to both physical and mental health problems. We examined cross-sectional relationships between work engagement and major health outcomes among junior and senior high school teachers in Japan via a nationwide survey in 2019-2020. A total of 3,160 respondents were included in the analyses (19.9% response rate). Work engagement was assessed with the Utrecht Work Engagement Scale-9 (UWES-9), and we thus divided the teachers into quartiles according to their UWES-9 scores. Based on validated questionnaires, we assessed insomnia, psychological distress, and neck pain as health outcomes. A binomial logistic regression adjusted for age, gender, school type, teacher’s roles, involvement in club activities, division of duties, employment status, and whether they lived with family demonstrated that the teachers with lower UWES-9 scores had higher burdens of insomnia, psychological distress, and neck pain (odds ratios [95% confidence intervals] in 4th vs. 1st quartile, 2.92 (2.34-3.65), 3.70 (2.81-4.88), and 2.12 (1.68-2.68), respectively; all trend p<0.001). There were no significant differences in these associations between full-time and part-time teachers. Our findings indicate that low work engagement may contribute to physical and mental health issues among junior and senior high school teachers, thus providing insights for preventing health problems in this profession. en-copyright= kn-copyright= en-aut-name=TsuchieRina en-aut-sei=Tsuchie en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukudaMari en-aut-sei=Fukuda en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsumuraHideki en-aut-sei=Tsumura en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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 Psychology, Graduate School of Technology, Industrial and Social Sciences, Tokushima University kn-affil= affil-num=4 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=work engagement kn-keyword=work engagement en-keyword=school teachers kn-keyword=school teachers en-keyword=insomnia kn-keyword=insomnia en-keyword=psychological distress kn-keyword=psychological distress en-keyword=neck pain kn-keyword=neck pain END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=81 end-page=92 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=Clinical Outcomes of Neoadjuvant Paclitaxel/Cisplatin/Gemcitabine Compared with Gemcitabine/Cisplatin for Muscle-Invasive Bladder Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=We retrospectively evaluated the oncologic outcomes of paclitaxel, cisplatin, and gemcitabine (PCG) with those of gemcitabine and cisplatin (GC) as neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients. The primary outcome was efficacy: pathological complete response (pCR), ypT0N0; and pathological objective response (pOR), ypT0N0, ? ypT1N0, or ypT0N1. Secondary outcomes included overall survival (OS), recurrence-free survival (RFS), predictive factors for pOR, OS, and RFS, and hematologic adverse events (AEs). Among 113 patients treated (PCG, n=28; GC, n=85), similar pOR and pCR rates were achieved by the groups (pOR: PCG, 57.1% vs. GC, 49. 4%; p=0.52; pCR: PCG, 39.3% vs. GC, 29.4%; p=0.36). No significant differences were observed in OS (p=1.0) or RFS (p=0.20). Multivariate logistic regression analysis showed that hydronephrosis (odds ratio [OR] 0.32, 95%CI: 0.11-0.92) and clinical node-positive status (cN+) (OR 0.22, 95%CI: 0.050-0.99) were significantly associated with a decreased probability of pOR. On multivariate Cox regression analyses, pOR achievement was associated with improved OS (hazard ratio [HR] 0.23, 95%CI: 0.10-0.56) and RFS (HR 0.30, 95%CI: 0.13-0.67). There were no significant between-group differences in the incidence of grade ? 3 hematologic AEs or dose-reduction required, but the PCG group had a higher incidence of grade 4 neutropenia. en-copyright= kn-copyright= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsugawaTakuji en-aut-sei=Tsugawa en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuboiKazuma en-aut-sei=Tsuboi en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro 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=KobayashiTomoko en-aut-sei=Kobayashi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EbaraShin en-aut-sei=Ebara en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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, Hiroshima City Hiroshima Citizens 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, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=urothelial carcinoma kn-keyword=urothelial carcinoma en-keyword=paclitaxel kn-keyword=paclitaxel en-keyword=cisplatin kn-keyword=cisplatin en-keyword=gemcitabine kn-keyword=gemcitabine en-keyword=neoadjuvant kn-keyword=neoadjuvant END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=65 end-page=73 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=Association between the Pretreatment Body Mass Index and Anamorelin’s Efficacy in Patients with Cancer Cachexia: A Retrospective Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Anamorelin (ANAM) is used to treat cancer-associated cachexia, a syndrome involving muscle loss and anorexia. The timing of the initiation of ANAM treatment is crucial to its efficacy. Although the body mass index (BMI) is a diagnostic criterion for cancer cachexia, no studies have explored its association with ANAM efficacy. We conducted a single-center, retrospective cohort study to investigate the association between the pre-treatment BMI and ANAM efficacy in patients with cancer-associated cachexia (n=47). The ANAM treatment was considered effective if the patient’s appetite improved within 30 days of treatment initiation. We calculated a BMI cutoff value (19.5 kg/m2) and used it to divide the patients into high- and low-BMI groups. Their background, clinical laboratory values, cancer types, and treatment lines were investigated. Twenty (42.6%) had a high BMI (? 19.5 kg/m2) and 27 (57.4%) had a low BMI (< 19.5 kg/m2). High BMI was significantly associated with ANAM effectiveness (odds ratio 7.86, 95% confidence interval 1.99-31.00, p=0.003). Together these results indicate that it is beneficial to initiate ANAM treatment before a patient’s BMI drops below 19.5 kg/m2. Our findings will help advance cancer cachexia treatment and serve as a reference for clinicians to predict ANAM’s efficacy. en-copyright= kn-copyright= en-aut-name=MakiMasatoshi en-aut-sei=Maki en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakadaRyo en-aut-sei=Takada en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshigoTomoyuki en-aut-sei=Ishigo en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiwaraMiki en-aut-sei=Fujiwara en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiYoko en-aut-sei=Takahashi en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=TamuraKoji en-aut-sei=Tamura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HamaokaTerutaka en-aut-sei=Hamaoka en-aut-mei=Terutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= affil-num=2 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= affil-num=3 en-affil=Department of Pharmacy, Sapporo Medical University Hospital kn-affil= affil-num=4 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= affil-num=5 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= affil-num=6 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=7 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= affil-num=8 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= en-keyword=anamorelin kn-keyword=anamorelin en-keyword=cancer-associated cachexia kn-keyword=cancer-associated cachexia en-keyword=body mass index kn-keyword=body mass index en-keyword=albumin kn-keyword=albumin en-keyword=efficacy rate kn-keyword=efficacy rate END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=12633 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association of emergency intensive care unit occupancy due to brain-dead organ donors with ambulance diversion en-subtitle= kn-subtitle= en-abstract= kn-abstract=Our study aims to explore how intensive care unit (ICU) occupancy by brain-dead organ donors affects emergency ambulance diversions. In this retrospective, single-center study at an emergency ICU (EICU), brain-dead organ donors were managed until organ procurement. We classified each day between August 1, 2021, and July 31, 2023, as either an exposure day (any day with a brain-dead organ donor in the EICU from admission to organ procurement) or a control day (all other days). The study compared these days and used multiple logistic regression analysis to assess the impact of EICU occupancy by brain-dead organ donors on ambulance diversions. Over two years, 6,058 emergency patients were transported by ambulance, with 1327 admitted to the EICU, including 13 brain-dead organ donors. Brain-dead donors had longer EICU stays (17 vs. 2 days, P < 0.001). With 168 exposure and 562 control days, EICU occupancy was higher on exposure days (75% vs. 67%, P = 0.003), leading to more ambulance diversions. Logistic regression showed exposure days significantly increased ambulance diversions, with an odds ratio of 1.79 (95% CIs 1.10-2.88). This study shows that managing brain-dead organ donors in the EICU leads to longer stays and higher occupancy, resulting in more frequent ambulance diversions. These findings highlight the critical need for policies that optimize ICU resource allocation while maintaining the infrastructure necessary to support organ donation programs and ensuring continued care for brain-dead donors, who play an essential role in addressing the organ shortage crisis. en-copyright= kn-copyright= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HongoTakashi en-aut-sei=Hongo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=HisamuraMasaki en-aut-sei=Hisamura en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Ambulance diversion kn-keyword=Ambulance diversion en-keyword=Bed occupancy kn-keyword=Bed occupancy en-keyword=Brain death kn-keyword=Brain death en-keyword=Emergency medical services kn-keyword=Emergency medical services en-keyword=Intensive care units kn-keyword=Intensive care units en-keyword=Organ donation kn-keyword=Organ donation 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=2025 dt-pub=20250410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enterobacterial common antigen repeat-unit flippase WzxE is required for Escherichia coli growth under acidic conditions, low temperature, and high osmotic stress conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Colanic acid and enterobacterial common antigen (ECA) are cell-surface polysaccharides that are produced by many Escherichia coli isolates. Colanic acid is induced under acidic, low temperature, and high-salt conditions and is important for E. coli resistance to these stresses; however, the role of ECA in these stresses is less clear. Here, we observed that knockout of flippase wzxE, which translocates lipid-linked ECA repeat units from the cytoplasmic side of the inner membrane to the periplasmic side, resulted in the sensitivity of E. coli BW25113 to acidic conditions. The wzxE-knockout mutant showed reduced growth potential and viable counts in vegetable extracts with acidic environments, including cherry tomatoes, carrots, celery, lettuce, and spinach. A double-knockout strain of wzxE and wecF (glycosyltransferase that adds the third-and-final sugar of the lipid-linked ECA repeat unit) was not sensitive to acidic conditions, with similar results obtained for a double-knockout strain of wzxE and wcaJ (glycosyltransferase that initiates colanic acid lipid-linked repeat-unit biosynthesis). The wzxE-knockout mutant was sensitive to low temperatures or high-salt conditions, which induced colanic acid synthesis, and these sensitivities were abolished by the additional knockout of wcaJ. These results suggest that lipid-linked ECA repeat units confer E. coli susceptibility to acidic, low temperatures, and high-salt conditions in a colanic acid-dependent manner and that wzxE suppresses this negative effect. en-copyright= kn-copyright= en-aut-name=YamaguchiSaki en-aut-sei=Yamaguchi en-aut-mei=Saki 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=FurutaKazuyuki en-aut-sei=Furuta en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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= en-keyword=wzxE flippase kn-keyword=wzxE flippase en-keyword=enterobacterial common antigen kn-keyword=enterobacterial common antigen en-keyword=low pH kn-keyword=low pH en-keyword=low temperature kn-keyword=low temperature en-keyword=hyperosmotic stress kn-keyword=hyperosmotic stress END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=7 article-no= start-page=2221 end-page= 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=Length Estimation of Pneumatic Artificial Muscle with Optical Fiber Sensor Using Machine Learning en-subtitle= kn-subtitle= en-abstract= kn-abstract=A McKibben artificial muscle is a soft actuator driven by air pressure, characterized by its flexibility, lightweight design, and high power-to-weight ratio. We have developed a smart artificial muscle that is capable of sensing its motion. To enable this sensing function, an optical fiber was integrated into the sleeve consisting of multiple fibers and serving as a component of the McKibben artificial muscle. By measuring the macrobending loss of the optical fiber, the length of the smart artificial muscle is expected to be estimated. However, experimental results indicated that the sensor's characteristics depend not only on the length but also on the load and the applied air pressure. This dependency arises because the stress applied to the optical fiber increases, causing microbending loss. In this study, we employed a machine learning model, primarily composed of Long Short-Term Memory (LSTM) neural networks, to estimate the length of the smart artificial muscle. The experimental results demonstrate that the length estimation obtained through machine learning exhibits a smaller error. This suggests that machine learning is a feasible approach to enhancing the length measurement accuracy of the smart artificial muscle. en-copyright= kn-copyright= en-aut-name=NiYilei en-aut-sei=Ni en-aut-mei=Yilei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WakimotoShuichi en-aut-sei=Wakimoto en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TianWeihang en-aut-sei=Tian en-aut-mei=Weihang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TodaYuichiro en-aut-sei=Toda en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KandaTakefumi en-aut-sei=Kanda en-aut-mei=Takefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamaguchiDaisuke en-aut-sei=Yamaguchi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=McKibben artificial muscle kn-keyword=McKibben artificial muscle en-keyword=machine learning kn-keyword=machine learning en-keyword=optical fiber kn-keyword=optical fiber en-keyword=motion estimation kn-keyword=motion estimation END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=7 article-no= start-page=2287 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of Midazolam and Diazepam for Sedation in Patients Undergoing Double-Balloon Endoscopic Retrograde Cholangiopancreatography: A Propensity Score-Matched Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: The sedation method used in double-balloon endoscopic retrograde cholangiopancreatography (DB-ERCP) varies across countries and between healthcare facilities. No previous studies have compared the effects of different benzodiazepines on sedation during endoscopic procedures. This study aimed to compare the effects of midazolam and diazepam sedation on DB-ERCP outcomes. Methods: This retrospective cohort study analyzed consecutive patients who underwent DB-ERCP between January 2017 and February 2024. A total of 203 patients who were sedated with diazepam (n = 94) or midazolam (n = 109) were analyzed. Propensity score matching was applied to adjust for baseline group differences. The primary outcome was the incidence of sedation-related adverse events (AEs). Secondary outcomes included inadequate sedation requiring additional sedatives and risk factors for sedation-related AEs. Results: Sedation-related AEs were more frequent with diazepam (28% [21/75]) than with midazolam (14% [11/75]; p = 0.046). Hypoxia occurred more frequently with diazepam (19% [14/75]) than with midazolam (5% [4/75]; p = 0.012). However, no significant differences were observed between the two groups for hypotension (p = 0.41) and bradycardia (p = 1.0). Poor sedation requiring other sedatives occurred significantly more often with diazepam (8% [6/75]) compared with midazolam sedation (0% [0/75], p = 0.012). Multivariate analysis identified diazepam sedation (odds ratio, 2.3; 95% confidence interval, 1.0-5.3; p = 0.048) as the sole risk factor for sedation-related AEs. Conclusions: Midazolam is safer and more effective than diazepam sedation in patients undergoing DB-ERCP. en-copyright= kn-copyright= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= en-keyword=adverse events kn-keyword=adverse events en-keyword=balloon-assisted ERCP kn-keyword=balloon-assisted ERCP en-keyword=benzodiazepine kn-keyword=benzodiazepine en-keyword=sedation kn-keyword=sedation END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=7 article-no= start-page=2242 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Lifestyle Changes on Body Weight Gain During Nationwide Lockdown Due to COVID-19 Pandemic en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: During the coronavirus disease 2019 (COVID-19) pandemic, people in Japan were urged to stay at home as much as possible, and this resulted in significant changes in lifestyle behavior. The new lifestyle included factors affecting both energy intake and energy consumption, and it is now thought that weight gain during the lockdown was the result of complex effects. The aim of this study was to determine the relationships among lifestyle habits, laboratory data, and body weight gain during the lockdown using medical check-up data. Methods: A total of 3789 individuals who had undergone consecutive medical check-ups during the period from 2018 to 2020 were included in this study. Participants whose body weight had increased by 5% or more were divided into two groups: a before-lockdown group (participants who had gained weight between 2018 and 2019) and an after-lockdown group (participants who had gained weight between 2019 and 2020). Physical measurements, laboratory data, and answers to six questions about lifestyle habits, for which information was obtained from the records from medical check-ups, were compared in the two groups. Results: There was no significant difference between the distribution of weight changes in 2018-2019 before the lockdown and the distribution of weight changes in 2019-2020 after the lockdown. The before-lockdown and after-lockdown groups both included about 7% of the total participants (279 and 273 participants, respectively). Diastolic blood pressure and levels of AST, ALT, and LDL-C were significantly higher in the after-lockdown group than in the before-lockdown group. The percentages of participants with alcohol consumption and exercise habits were significantly higher in the after-lockdown group than in the before-lockdown group, and an analysis by gender showed that the differences were significant for women but not for men. Conclusions: The distributions of weight changes before and during the COVID-19 pandemic were similar. Exercise habits and alcohol consumption might have been unique factors causing weight gain during the COVID-19 pandemic, particularly in women. Our findings suggest that the impact of behavioral restrictions and lifestyle changes during a pandemic may be different in men and women. en-copyright= kn-copyright= en-aut-name=NishidaChisa en-aut-sei=Nishida en-aut-mei=Chisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanoYasuhiro en-aut-sei=Nakano en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TokumasuKazuki en-aut-sei=Tokumasu en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=ObikaMikako en-aut-sei=Obika en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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= en-keyword=COVID-19 pandemic kn-keyword=COVID-19 pandemic en-keyword=lockdown kn-keyword=lockdown en-keyword=weight gain kn-keyword=weight gain en-keyword=medical check-ups kn-keyword=medical check-ups en-keyword=lifestyle kn-keyword=lifestyle END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=2 article-no= start-page=100016 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Changes in adrenoceptor expression level contribute to the cellular plasticity of glioblastoma cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Glioblastoma cells are known to regulate their cellular plasticity in response to their surrounding microenvironment, but it is not fully understood what factors contribute to the cells' changing plasticity. Here, we found that glioblastoma cells alter the expression level of adrenoreceptors depending on their differentiation stage. Catecholamines are abundant in the central nervous system, and we found that noradrenaline, in particular, enhances the stemness of glioblastoma cells and promotes the dedifferentiation potential of already differentiated glioblastoma cells. Antagonist and RNAi experiments revealed that signaling through alpha 1D-adrenoreceptor is important for noradrenaline action on glioblastoma cells. We also found that high alpha 1Dadrenoreceptor expression was associated with poor prognosis in patients with gliomas. These data suggest that glioblastoma cells increase the expression level of their own adrenoreceptors to alter the surrounding tumor microenvironment favorably for survival. We believe that our findings will contribute to the development of new therapeutic strategies for glioblastoma. en-copyright= kn-copyright= en-aut-name=AsakaYutaro en-aut-sei=Asaka en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MasumotoToshio en-aut-sei=Masumoto en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UnedaAtsuhito en-aut-sei=Uneda en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChinVanessa D. en-aut-sei=Chin en-aut-mei=Vanessa D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtaniYusuke en-aut-sei=Otani en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=PenaTirso en-aut-sei=Pena en-aut-mei=Tirso kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= en-aut-name=AndoTeruhiko en-aut-sei=Ando en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HuangRongsheng en-aut-sei=Huang en-aut-mei=Rongsheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Division of Health Administration and Promotion, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=3 en-affil=Department of Neurosurgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=UMass Chan Medical School, UMass Memorial Medical Center kn-affil= affil-num=5 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=6 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Trauma Orthopedics, The Second Hospital of Dalian Medical University kn-affil= affil-num=11 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Adrenoceptors kn-keyword=Adrenoceptors en-keyword=Glioma stem-like cells kn-keyword=Glioma stem-like cells en-keyword=Differentiated glioma cells kn-keyword=Differentiated glioma cells en-keyword=Noradrenaline kn-keyword=Noradrenaline en-keyword=Cellular plasticity kn-keyword=Cellular plasticity 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=2025 dt-pub=20250403 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The association between objectively measured physical activity and home blood pressure: a population-based real-world data analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Few studies have examined the association of objectively measured habitual physical activity (PA) and sedentary behavior with out-of-office blood pressure (BP). We investigated the associations of objectively measured PA intensity time, sedentary time, and step count with at-home BP. Using accelerometer-recorded PA indices and self-measured BP in 368 participants (mean age, 53.8 years; 58.7% women), we analyzed 115,575 records of each parameter between May 2019 and April 2024. PA intensities were categorized as light (2.0?2.9 metabolic equivalents [METs]); moderate (3.0?5.9 METs); vigorous (?6.0 METs), or sedentary (<2.0 METs): the median [interquartile ranges] for these variables was 188 [146?232], 83 [59?114], 1 [0?2], 501 [428?579] minutes, respectively, and for step count, was 6040 [4164?8457]. Means [standard deviations] for systolic and diastolic BP were 116.4 [14.2] and 75.2 [9.3] mmHg, respectively. A mixed-effect model adjusted for possible confounders showed that 1-h longer in vigorous PA was associated with lower systolic and diastolic BP (?1.69 and ?1.09?mmHg, respectively). A 1000-step increase in step count was associated with lower systolic and diastolic BP (?0.05 and ?0.02?mmHg, respectively). Associations were more pronounced among men and participants aged <60 years. Sedentary time was positively associated with BP in men and participants aged <60 years, but inversely associated with BP in women and participants aged ?60 years. Our findings suggest that more PA and less sedentary behavior were associated with BP reduction, particularly among men and participants aged <60 years. However, the clinical relevance of this effect remains uncertain because of its modest magnitude. en-copyright= kn-copyright= en-aut-name=KinutaMinako en-aut-sei=Kinuta en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaniguchiKaori en-aut-sei=Taniguchi en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukudaMari en-aut-sei=Fukuda en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakahataNoriko en-aut-sei=Nakahata en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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 Environmental Medicine and Public Health, Izumo, Shimane University Faculty of Medicine kn-affil= affil-num=4 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Health and Nutrition, The University of Shimane Faculty of Nursing and Nutrition kn-affil= affil-num=6 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=213 cd-vols= no-issue= article-no= start-page=128 end-page=137 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=The potential mechanism maintaining transactive response DNA binding protein 43?kDa in the mouse stroke model en-subtitle= kn-subtitle= en-abstract= kn-abstract=The disruption of transactive response DNA binding protein 43?kDa (TDP-43) shuttling leads to the depletion of nuclear localization and the cytoplasmic accumulation of TDP-43. We aimed to evaluate the mechanism underlying the behavior of TDP-43 in ischemic stroke. Adult male C57BL/6?J mice were subjected to 30 or 60?min of transient middle cerebral artery occlusion (tMCAO), and examined at 1, 6, and 24?h post reperfusion. Immunostaining was used to evaluate the expression of TDP-43, G3BP1, HDAC6, and RAD23B. The total and cytoplasmic number of TDP-43?positive cells increased compared with sham operation group and peaked at 6?h post reperfusion after tMCAO. The elevated expression of G3BP1 protein peaked at 6?h after reperfusion and decreased at 24?h after reperfusion in ischemic mice brains. We also observed an increase of expression level of HDAC6 and the number of RAD23B-positive cells increased after tMCAO. RAD23B was colocalized with TDP-43 24?h after tMCAO. We proposed that the formation of stress granules might be involved in the mislocalization of TDP-43, based on an evaluation of G3BP1 and HDAC6. Subsequently, RAD23B, may also contribute to the downstream degradation of mislocalized TDP-43 in mice tMCAO model. en-copyright= kn-copyright= en-aut-name=BianYuting en-aut-sei=Bian en-aut-mei=Yuting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukuiYusuke en-aut-sei=Fukui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Ota-ElliottRicardo Satoshi en-aut-sei=Ota-Elliott en-aut-mei=Ricardo Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HuXinran en-aut-sei=Hu en-aut-mei=Xinran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SunHongming en-aut-sei=Sun en-aut-mei=Hongming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BianZhihong en-aut-sei=Bian en-aut-mei=Zhihong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhaiYun en-aut-sei=Zhai en-aut-mei=Yun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YuHaibo en-aut-sei=Yu en-aut-mei=Haibo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HuXiao en-aut-sei=Hu en-aut-mei=Xiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AnHangping en-aut-sei=An en-aut-mei=Hangping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=LiuHongzhi en-aut-sei=Liu en-aut-mei=Hongzhi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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 Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=TDP-43 kn-keyword=TDP-43 en-keyword=ALS kn-keyword=ALS en-keyword=RNA-binding protein kn-keyword=RNA-binding protein en-keyword=Mislocalization kn-keyword=Mislocalization en-keyword=G3BP1 kn-keyword=G3BP1 en-keyword=HDAC6 kn-keyword=HDAC6 en-keyword=RAD23B kn-keyword=RAD23B en-keyword=tMCAO kn-keyword=tMCAO END